Healthy VolunteerPhase 1NCT04147715
Evaluation of Safety, Tolerability, Pharmacokinetics, Drug-Drug and Food Interactions of Single and Multiple Doses of S-648414 in Healthy Adults
A Phase 1 study testing S-648414, Midazolam and Dolutegravir in people with Healthy Volunteer, run by Shionogi at 2 sites in 2 countries.
Trial summary
The primary objective of Part 1 of the study is to evaluate the safety and tolerability of S-648414 after administration of a single oral dose of S-648414 in healthy adult study participants. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteer
- What is being tested?
- S-648414, Midazolam and Dolutegravir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 98 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 9 Oct 2019to 29 Sep 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or female adults ≥ 18 years in USA or ≥ 20 years in Japan to ≤ 55 years of age, at the time of signing the informed consent form (ICF).
- Specific to Japan sites: enrollment in Part 3 (Group I and J) will consist of only White or Black or African American race.
- Capable of giving signed informed consent
- Body mass index (BMI) ≥ 18.5 to < 32.0 kg/m² at the Screening visit．
- Considered medically healthy as determined by the investigator or subinvestigator (suitably qualified), based on medical history and clinical evaluations including physical examination, clinical laboratory tests, vital sign measurements, and 12-lead electrocardiogram (ECG) at Screening and at upon admission to the Clinical Research Unit (CRU) and prior to administration of study intervention on Day 1.
- Female study participants must not be a woman of childbearing potential and must either be postmenopausal (defined as no menses for 12 months without an alternative medical cause; follicle-stimulating hormone (FSH) to be tested for confirmation at Screening) or premenopausal with 1 of the following documented: hysterectomy, tubal ligation, bilateral salpingectomy, or bilateral oophorectomy.
- Male study participants must agree to use contraception during the treatment period and for at least 3 months after the last dose of study intervention.
Who cannot join
- Considered by the investigator or subinvestigator (suitably qualified) to be ineligible for the study due to a history of or current condition of significant metabolic or endocrine, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal (GI), urological, immunological, neurological, or psychiatric disorders with clinical manifestations.
- History or presence of cancer in last 5 years except for non-melanoma skin cancers.
- Risk factors for:
- Torsades de Pointes (eg, heart failure, cardiomyopathy, or family history of Long QT Syndrome or Brugada Syndrome)
- Unexplained syncope, sick sinus syndrome, second- or third-degree atrioventricular (AV) block, myocardial infarction, pulmonary congestion, cardiac arrhythmia, angina, prolonged QT interval, or conduction abnormalities
- History of GI surgery or disease including, but not limited to, gastric band/gastric resection and/or intestinal resection and/or duodenal disease (ie, celiac disease) that may result in clinically significant malabsorption (except for an appendectomy).
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- History of hypersensitivity or severe side effects induced by a drug.
- Any condition requiring medication and/or other treatment, such as dietary restriction and physical therapy.
- History of significant multiple and/or severe allergic symptoms including food allergy (NOTE: Study participants with seasonal allergies may participate unless they have ongoing symptoms).
- Used drugs or substances known to be inducers or inhibitors of cytochrome P450 enzymes and/or P-glycoprotein within 28 days prior to admission to the CRU.
- Used prescription or over-the-counter (OTC) drugs, antacids, proton pump inhibitors, H2 antagonists, Chinese herbal medicines, oral cannabidiol, vitamins, minerals, herbal, and dietary supplements within 14 days prior to admission to the CRU.
- Refuses to abstain from ingesting caffeine- or xanthine-containing products/medications (eg, coffee, tea, cola drinks, other caffeinated beverages, or chocolate) from 24 hours prior to admission to the CRU or refuses to refrain from consuming such products throughout the study (including Follow-up period).
- Consumed alcohol or used alcohol-containing products within 72 hours prior to admission to the CRU or refuses to refrain from consuming such products throughout the study (including Follow-up period).
- History of recreational drug use in the previous 6 months, or has a history of problematic alcohol use (defined as study participants who regularly consume excessive amounts of alcohol, defined as > 3 glasses of alcoholic beverages per day (1 glass is approximately equivalent to: beer [284 mL/10 ounces (oz.)], wine [125 mL/4 oz.] or distilled spirits [25 mL/1 oz.]).
- A positive drug or alcohol screen at the Screening visit or upon admission to the CRU.
- Used tobacco- or nicotine-containing products (including cigarette, pipe, cigar, chewing, nicotine patch, nicotine gum, or Vaping product) within 6 months prior to admission to the CRU or refuses to refrain from using tobacco- or nicotine-containing products throughout the study (including Follow-up period).
- Consumed grapefruit, grapefruit juice, Seville orange juice, orange juice, apple juice, vegetables from the mustard green family (eg, kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard greens), or charbroiled meats within 7 days prior to admission to the CRU or refuses to refrain from consuming such products throughout the study (including Follow-up period).
- A corrected QT (QTc) interval of > 450 msec for males and > 470 msec for females (Fridericia's method) at the Screening visit or upon admission to the CRU.
- Systolic blood pressure is outside the range of 90 to 140 mm Hg, diastolic blood pressure is outside the range of 50 to 90 mm Hg, or pulse rate is outside the range of 40 to 100 beats per minute (bpm) or considered ineligible by the investigator or subinvestigator at the Screening visit or upon admission to the CRU.
- Total bilirubin, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) values are greater than the upper limit of normal (ULN), or estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m² at Screening or upon admission to the CRU.
- A positive serological test for untreated syphilis, positive hepatitis B surface antigen, positive hepatitis C virus antibody, or positive human immunodeficiency virus (HIV) antigen/antibody result at the Screening visit.
- Participated in any other investigational trials or has been exposed to other investigational drugs within 28 days or 5 half-lives of the previously administered investigational drug (date derived from last study procedure [blood collection or dosing] of previous trial), whichever is longer, prior to admission to the CRU.
- Previously received S-648414.
- Poor venous access.
- Donated blood or had significant blood loss within 56 days of study admission to the CRU or donated plasma within 7 days prior to until admission to the CRU.
- Considered inappropriate for participation in the study for any reason by the investigator or subinvestigator.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
PPD Ph 1 Clinical Research Unit
Austin, Texas, 78744
About this study
Official title: A Phase 1, Randomized, Double-Blind, Single-Ascending-Dose, and Food Effect Study to Assess the Safety, Tolerability, Ventricular Repolarization, and Pharmacokinetics of S-648414 in Healthy Adult Study Participants (Part 1); A Phase 1, Randomized, Double-Blind, Multiple-Ascending-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of S-648414 and A Drug-Drug Interaction Study With the CYP3A Substrate, Midazolam, in Healthy Adult Study Participants (Part 2)
The primary objective of Part 1 of the study is to evaluate the safety and tolerability of S-648414 after administration of a single oral dose of S-648414 in healthy adult study participants.
The primary objective of Part 2 is to evaluate the safety and tolerability of S-648414 after administration of multiple oral doses of S-648414 in healthy adult study participants.
The primary objectives of Part 3 are evaluate the safety and tolerability of S-648414 after administration of multiple oral doses of S-648414 in healthy adult study participants, and to evaluate the effect of S-648414 on the pharmacokinetics (PK) of dolutegravir and the effect of dolutegravir on the PK of S-648414 in healthy adult study participants.
Read the detailed description
Amendment 2 of the study Protocol added a third part (Part 3) to the study. The revised Official Title for the Protocol is:
"A Phase 1, Randomized, Double-Blind, Single-Ascending-Dose, and Food Effect Study to Assess the Safety, Tolerability, Ventricular Repolarization, and Pharmacokinetics of S-648414 in Healthy Adult Study Participants (Part 1); A Phase 1, Randomized, Double-Blind, Multiple-Ascending-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of S-648414 and A Drug-Drug Interaction Study with the CYP3A Substrate, Midazolam, in Healthy Adult Study Participants (Part 2); and A Phase 1 Open-Label Study to Assess the Effect of S-648414 on the Pharmacokinetics of Dolutegravir and the Effect of Dolutegravir on the Pharmacokinetics of S-648414 in Healthy Adult Study Participants (Part 3)"
- Conditions
- Healthy Volunteer
- Being tested
- S-648414, Placebo, Midazolam, Dolutegravir
- Keywords
- Pharmacokinetics, S-648414, Food effect, Antiretroviral, Drug-drug interaction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
S-648414Drug
Tablet for oral administration
PlaceboDrug
Tablet for oral administration
MidazolamDrug
Also called Versed
Solution for oral administration
DolutegravirDrug
Also called TIVICAY
Tablet for oral administration
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Placebo | Placebo comparator | Participants received a single oral dose of matching placebo in a fasted state on Day 1. Receives: Drug: Placebo |
| Part 1: 10 mg S-648414 | Experimental | Participants received a single oral dose of 10 mg S-648414 in a fasted state on Day 1. Receives: Drug: S-648414 |
| Part 1: 30 mg S-648414 | Experimental | Participants received a single oral dose of 30 mg S-648414 in a fasted state on Day 1. Receives: Drug: S-648414 |
| Part 1: 100 mg S-648414 | Experimental | Participants received a single oral dose of 100 mg S-648414 in a fasted state on Day 1 followed by a single dose of S-648414 in a fed state (after a high-fat meal) on Day 14. Receives: Drug: S-648414 |
| Part 1: 250 mg S-648414 | Experimental | Participants received a single oral dose of 250 mg S-648414 in a fasted state on Day 1. Receives: Drug: S-648414 |
| Part 1: 500 mg S-648414 | Experimental | Participants received a single oral dose of 500 mg S-648414 in a fasted state on Day 1. Receives: Drug: S-648414 |
| Part 1: 1000 mg S-648414 | Experimental | Participants received a single oral dose of 1000 mg S-648414 in a fasted state on Day 1. Receives: Drug: S-648414 |
| Part 2: Placebo + Midazolam | Placebo comparator | Participants received matching placebo once a day on Days 1 to 14 and a single oral dose of 5 mg midazolam alone on Day -2 and co-administered with the placebo dose on Day 14. Receives: Drug: Placebo; Drug: Midazolam |
| Part 2: 50 mg S-648414 + Midazolam | Experimental | Participants received 50 mg S-648414 once a day on Days 1 to 14 and a single oral dose of 5 mg midazolam alone on Day -2 and co-administered with the S-648414 dose on Day 14. Receives: Drug: S-648414; Drug: Midazolam |
| Part 2: 30 mg S-648414 + Midazolam | Experimental | Participants received 30 mg S-648414 once a day on Days 1 to 14 and a single oral dose of 5 mg midazolam alone on Day -2 and co-administered with the S-648414 dose on Day 14. Receives: Drug: S-648414; Drug: Midazolam |
| Part 3: 100 mg S-648414 + Dolutegravir | Experimental | Participants received 50 mg dolutegravir orally once a day on Days 1 to 7, 100 mg S-648414 orally once a day on Days 15 to 21, and 50 mg dolutegravir co-administered with 100 mg S-648414 orally once a day on Days 22 to 28. Receives: Drug: S-648414; Drug: Dolutegravir |
| Part 3: 200 mg S-648414 + Dolutegravir | Experimental | Participants received 50 mg dolutegravir orally once a day on Days 1 to 7, 200 mg S-648414 orally once a day on Days 15 to 21, and 50 mg dolutegravir co-administered with 200 mg S-648414 orally once a day on Days 22 to 28. Receives: Drug: S-648414; Drug: Dolutegravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
A TEAE is any event not present before exposure to study drug or any event already present that worsens after exposure to study drug.
A serious adverse event is any untoward medical occurrence that resulted in death, was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or other event that may have jeopardized the participant or required intervention to prevent one of the outcomes above.
The investigator assessed the intensity of each AE according to the following:
Grade 1 (Mild): No or minimal interference with usual activities.
Grade 2 (Moderate): More than minimal interference with usual activities, intervention indicated.
Grade 3 (Severe): Inability to perform usual activities, intervention or hospitalization indicated.
Grade 4 (Potentially life-threatening): Inability to perform self-care, intervention indicated to prevent permanent impairment, disability, or death.
Measured: From dosing on Day 1 or Day 14 up to 10 days post dose
Part 2: Number of Participants With Treatment-emergent Adverse Events
A TEAE is any event not present before exposure to study drug or any event already present that worsens after exposure to study drug.
A serious adverse event is any untoward medical occurrence that resulted in death, was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or other event that may have jeopardized the participant or required intervention to prevent one of the outcomes above.
The investigator assessed the intensity of each AE according to the following:
Grade 1 (Mild): No or minimal interference with usual activities.
Grade 2 (Moderate): More than minimal interference with usual activities, intervention indicated.
Grade 3 (Severe): Inability to perform usual activities, intervention or hospitalization indicated.
Grade 4 (Potentially life-threatening): Inability to perform self-care, intervention indicated to prevent permanent impairment, disability, or death.
Measured: From the first dose up to 10 days after end of dosing (25 days); A TEAE was summarized to a given treatment if the event onset/worsening occurred any time after the dose of that treatment and before the dose of the next treatment.
Part 3: Number of Participants With Treatment-emergent Adverse Events
A TEAE is any event not present before exposure to study drug or any event already present that worsens after exposure to study drug.
A serious adverse event is any untoward medical occurrence that resulted in death, was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or other event that may have jeopardized the participant or required intervention to prevent one of the outcomes above.
The investigator assessed the intensity of each AE according to the following:
Grade 1 (Mild): No or minimal interference with usual activities.
Grade 2 (Moderate): More than minimal interference with usual activities, intervention indicated.
Grade 3 (Severe): Inability to perform usual activities, intervention or hospitalization indicated.
Grade 4 (Potentially life-threatening): Inability to perform self-care, intervention indicated to prevent permanent impairment, disability, or death.
Measured: From the first dose up to Day 36; A TEAE was summarized to a given treatment if the event onset/worsening occurred any time after the dose of that treatment and before the dose of the next treatment.
Part 3: Maximum Plasma Concentration (Cmax) of S-648414
The effect of dolutegravir on the pharmacokinetics (PK) of S-648414 was assessed after administration of multiple oral doses of S-648414 alone (Day 21) and after administration of multiple oral doses of S-648414 co-administered with dolutegravir (Day 28).
Measured: Day 21 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose. Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 3: Time to Maximum Plasma Concentration (Tmax) of S-648414
The effect of dolutegravir on the pharmacokinetics (PK) of S-648414 was assessed after administration of multiple oral doses of S-648414 alone (Day 21) and after administration of multiple oral doses of S-648414 co-administered with dolutegravir (Day 28).
Measured: Day 21 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose. Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 3: Plasma Concentration of S-648414 at the End of the Dosing Interval τ (Cτ)
The effect of dolutegravir on the pharmacokinetics (PK) of S-648414 was assessed after administration of multiple oral doses of S-648414 alone (Day 21) and after administration of multiple oral doses of S-648414 co-administered with dolutegravir (Day 28).
Measured: Day 22 and Day 29 (24 hours post-dosing on Days 21 and 28)
Part 3: Area Under the Concentration-time Curve Over the Dosing Interval τ (AUC0-τ) for S-648414
The effect of dolutegravir on the pharmacokinetics (PK) of S-648414 was assessed after administration of multiple oral doses of S-648414 alone (Day 21) and after administration of multiple oral doses of S-648414 co-administered with dolutegravir (Day 28).
Area under the concentration-time curve over the dosing interval τ (24 hours) was calculated by the linear up/log down trapezoidal method.
Measured: Day 21 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose. Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 3: Apparent Total Clearance (CL/F) of S-648414
The effect of dolutegravir on the pharmacokinetics (PK) of S-648414 was assessed after administration of multiple oral doses of S-648414 alone (Day 21) and after administration of multiple oral doses of S-648414 co-administered with dolutegravir (Day 28).
Apparent total clearance was calculated as CL/F = Dose/AUC0-τ
Measured: Day 21 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose. Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 3: Maximum Plasma Concentration (Cmax) of Dolutegravir
The effect of S-648414 on the PK of dolutegravir was assessed after administration of multiple oral doses of dolutegravir alone and after administration of multiple oral doses of S-648414 co-administered with dolutegravir.
Measured: Day 7 and Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours postdose.
Part 3: Time to Maximum Plasma Concentration (Tmax) of Dolutegravir
The effect of S-648414 on the PK of dolutegravir was assessed after administration of multiple oral doses of dolutegravir alone and after administration of multiple oral doses of S-648414 co-administered with dolutegravir.
Measured: Day 7 and Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours postdose.
Part 3: Plasma Concentration of Dolutegravir at the End of the Dosing Interval τ (Cτ)
The effect of S-648414 on the PK of dolutegravir was assessed after administration of multiple oral doses of dolutegravir alone and after administration of multiple oral doses of S-648414 co-administered with dolutegravir.
Measured: Day 8 and Day 29 (24 hours post-dosing on Day 7 and Day 28).
Part 3: Area Under the Concentration-time Curve Over the Dosing Interval τ (AUC0-τ) for Dolutegravir
The effect of S-648414 on the PK of dolutegravir was assessed after administration of multiple oral doses of dolutegravir alone and after administration of multiple oral doses of S-648414 co-administered with dolutegravir.
Area under the concentration-time curve over the dosing interval τ (24 hours) was calculated by the linear up/log down trapezoidal method.
Measured: Day 7 and Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours postdose.
Part 3: Apparent Total Clearance (CL/F) of Dolutegravir
The effect of S-648414 on the PK of dolutegravir was assessed after administration of multiple oral doses of dolutegravir alone and after administration of multiple oral doses of S-648414 co-administered with dolutegravir.
Apparent total clearance calculated as CL/F =Dose/AUC0-τ
Measured: Day 7 and Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours postdose.
Secondary outcomes (37)
Part 1: Maximum Plasma Concentration (Cmax) of S-648414
Measured: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.
Part 1: Time to Maximum Plasma Concentration (Tmax) of S-648414
Measured: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.
Part 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration After Dosing (AUC0-last) of S-648414
Area under the concentration-time curve from time zero to the time of the last quantifiable concentration after dosing, calculated by the linear trapezoidal method when concentrations are increasing and by the logarithmic trapezoidal method when concentrations are decreasing (linear up/log down trapezoidal method).
Measured: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.
Part 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of S-648414
Area under the concentration-time curve extrapolated from time zero to infinity defined as AUC0-last + (Clast/λz), where Clast is the last measurable plasma concentration and λz is the plasma terminal elimination rate constant.
Measured: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.
Part 1: Terminal Elimination Half-life (t1/2,z) of S-648414
Terminal elimination half-life calculated as t1/2,z = (ln2)/λz, where λz is the terminal elimination rate constant.
Measured: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.
Part 1: Terminal Elimination Rate Constant (λz) of S-648414
Measured: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.
Part 1: Mean Residence Time (MRT) of S-648414
Mean residence time, calculated as MRT = AUMC0-inf / AUC0-inf, where AUMC0-inf is the area under the first moment curve extrapolated to infinity.
Measured: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.
Part 1: Apparent Total Clearance (CL/F) of S-648414
Apparent total clearance estimated according to: CL/F = Dose / AUC0-inf.
Measured: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.
Part 1: Apparent Volume of Distribution in the Terminal Elimination Phase (Vz/F) of S-648414
Apparent volume of distribution in the terminal elimination phase was estimated according to: Vz /F = Dose / AUC0-inf / λz.
Measured: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.
Part 1: Fraction of S-648414 Dose Excreted in Urine From 0 to 96 Hours Postdose (Feu0-96)
The fraction of S-648414 dose excreted in urine from 0 to 96 hours postdose was calculated as:
Cumulative amount of S-648414 excreted in urine from time zero to 96 hours postdose (Aeu0-96) / Dose × 100
Measured: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose (-12 to 0 hours), 0 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours postdose
Part 1: Renal Clearance (CLR) of S-648414
Renal clearance was estimated according to: CLR = cumulative amount of S-648414 excreted in urine from time zero to 96 hours postdose (Aeu0-96) / area under the concentration-time curve from time zero to the time of the last quantifiable concentration after dosing (AUC0-last).
Measured: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose (-12 to 0 hours), 0 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours postdose
Part 2: Maximum Plasma Concentration (Cmax) of S-648414 Following Single and Multiple-dose Administration
Measured: Day 1 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose; Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96 hours postdose.
Part 2: Time to Maximum Plasma Concentration (Tmax) of S-648414 Following Single and Multiple-dose Administration
Measured: Day 1 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose; Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96 hours postdose.
Part 2: Area Under the Concentration-time Curve Over the Dosing Interval τ (AUC0-τ) of S-648414 Following Single and Multiple-dose Administration
Area under the concentration-time curve over the dosing interval (24 hours) on Day 1 and Day 14, calculated by the linear up/log down trapezoidal method.
Measured: Day 1 and day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 2: Terminal Elimination Half-life (t1/2,z) of S-648414 Following Multiple-dose Administration
Terminal elimination half-life, where t1/2,z = (ln2)/λz on Day 14.
Measured: Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96 hours postdose.
Part 2: Terminal Elimination Rate Constant (λz) of S-648414 Following Multiple-dose Administration
Terminal elimination rate constant, where λz is the magnitude of the slope of the linear regression of the log concentration versus time profile during the terminal phase on Day 14.
Measured: Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96 hours postdose.
Part 2: Apparent Total Clearance (CL/F) of S-648414 Following Multiple-dose Administration
Apparent total clearance estimated according to: CL/F = Dose/AUC0-τ on Day 14
Measured: Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 2: Apparent Volume of Distribution in the Terminal Elimination Phase (Vz/F) of S-648414 Following Multiple-dose Administration
Apparent volume of distribution in the terminal elimination phase on Day 14, estimated according to: Vz /F = Dose/AUC0-τ/λz
Measured: Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96 hours postdose.
Part 2: Fraction of S-648414 Dose Excreted in Urine Over the Dosing Interval (Feu0- τ) Following Multiple-dose Administration
Fraction of dose excreted in urine over the dosing interval τ (24 hours) on Day 14 calculated as Aeu0-τ/Dose × 100, where Aeu0-τ is the amount of drug excreted in urine over the dosing interval τ (24 hours).
Measured: Day 14 0-24 hours postdose
Part 2: Renal Clearance (CLR) of S-648414 Following Multiple-dose Administration
Renal clearance on Day 14, calculated as CLR = Aeu0-τ/AUC0-τ, where Aeu0-τ is the amount of drug excreted in urine over the dosing interval τ (24 hours)
Measured: Day 14 0-24 hours postdose
Part 2: Maximum Plasma Concentration (Cmax) of Midazolam
The effect of S-648414 on the PK of midazolam (a cytochrome P450 3A [CYP3A] substrate) was assessed in Part 2 following 5 mg midazolam administration alone (Day -2) and co-administration with S-648414 30 or 50 mg (Day 14).
Measured: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 2: Time to Maximum Plasma Concentration of Midazolam
The effect of S-648414 on the PK of midazolam (a cytochrome P450 3A [CYP3A] substrate) was assessed in Part 2 following 5 mg midazolam administration alone (Day -2) and co-administration with S-648414 30 or 50 mg (Day 14).
Measured: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 2: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration After Dosing (AUC0-last) for Midazolam
The effect of S-648414 on the PK of midazolam (a cytochrome P450 3A [CYP3A] substrate) was assessed in Part 2 following 5 mg midazolam administration alone (Day -2) and co-administration with S-648414 30 or 50 mg (Day 14).
Area under the concentration-time curve from time zero to the time of the last quantifiable concentration after dosing, calculated by linear up/log down trapezoidal method.
Measured: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 2: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Midazolam
The effect of S-648414 on the PK of midazolam (a cytochrome P450 3A [CYP3A] substrate) was assessed in Part 2 following 5 mg midazolam administration alone (Day -2) and co-administration with S-648414 30 or 50 mg (Day 14).
Area under the concentration-time curve extrapolated from time zero to infinity defined as AUC0-last + (Clast/λz), where Clast is the last measurable plasma concentration and λz is the plasma terminal elimination rate constant.
Measured: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 2: Terminal Elimination Half-life for Midazolam
The effect of S-648414 on the PK of midazolam (a cytochrome P450 3A [CYP3A] substrate) was assessed in Part 2 following 5 mg midazolam administration alone (Day -2) and co-administration with S-648414 30 or 50 mg (Day 14).
Measured: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 2: Terminal Elimination Rate Constant for Midazolam
The effect of S-648414 on the PK of midazolam (a cytochrome P450 3A [CYP3A] substrate) was assessed in Part 2 following 5 mg midazolam administration alone (Day -2) and co-administration with S-648414 30 or 50 mg (Day 14).
Measured: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 2: Mean Residence Time for Midazolam
The effect of S-648414 on the PK of midazolam (a cytochrome P450 3A [CYP3A] substrate) was assessed in Part 2 following 5 mg midazolam administration alone (Day -2) and co-administration with S-648414 30 or 50 mg (Day 14).
Mean residence time was calculated as MRT = AUMC0-inf/AUC0-inf where AUMC0-inf is the area under the first moment curve extrapolated to infinity.
Measured: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 1: Change From Baseline in Fridericia's Corrected QT Interval (QTcF)
Continuous 12-lead digital electrocardiogram (ECG) recording was performed on Day 1. The QT interval is a measure between Q and T wave in heart's electrical cycle. ECGs were analyzed at a blinded, central ECG laboratory. At each specified time point, ten 14-second 12-lead ECG tracings were extracted from the continuous recordings. The median QT in each replicate was calculated; the mean of available medians was used as the participant's reportable value at that time point.
QT interval was corrected for heart rate using Fridericia's correction (QTcF). Baseline was defined as the average of the measured ECG intervals from the 3 pre-dose time points (45, 30, and 15 minutes before dosing) on Day 1.
Change from Baseline (ΔQTcF) was calculated based on a linear mixed-effects model with time (categorical), treatment, and time-by-treatment interaction as fixed effects and Baseline QTcF as covariate.
Measured: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.
Parts 1: Change From Baseline in Heart Rate (HR)
Continuous 12-lead digital electrocardiogram (ECG) recording was performed on Day 1. ECGs were analyzed at a blinded, central ECG laboratory. At each specified time point, ten 14-second 12-lead ECG tracings were extracted from the continuous recordings. The median HR in each replicate was calculated; the mean of available medians was used as the participant's reportable value at that time point.
Baseline was defined as the average of the measured ECG values from the 3 pre-dose time points (45, 30, and 15 minutes before dosing) on Day 1.
Change from Baseline in HR (ΔHR) was calculated based on a linear mixed-effects model with time (categorical), treatment, and time-by-treatment interaction as fixed effects and Baseline HR as covariate.
Measured: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.
Part 1: Change From Baseline in PR Interval
Continuous 12-lead digital electrocardiogram (ECG) recording was performed on Day 1. The PR interval is the time from the onset of the P-wave to the start of the next QRS complex. ECGs were analyzed at a blinded, central ECG laboratory. At each specified time point, ten 14-second 12-lead ECG tracings were extracted from the continuous recordings. The median PR in each replicate was calculated; the mean of available medians was used as the participant's reportable value at that time point.
Baseline was defined as the average of the measured ECG intervals from the 3 pre-dose time points (45, 30, and 15 minutes before dosing) on Day 1.
Change from Baseline in PR interval (ΔPR) was calculated based on a linear mixed-effects model with time (categorical), treatment, and time-by-treatment interaction as fixed effects and Baseline PR as covariate.
Measured: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.
Part 1: Change From Baseline in QRS Interval
Continuous 12-lead digital electrocardiogram (ECG) recording was performed on Day 1. The QRS complex is a combination of the Q wave, R wave and S wave on an ECG tracing, and represents ventricular depolarization. ECGs were analyzed at a blinded, central ECG laboratory. At each specified time point, ten 14-second 12-lead ECG tracings were extracted from the continuous recordings. The median QRS in each replicate was calculated; the mean of available medians was used as the participant's reportable value at that time point.
Baseline was defined as the average of the measured ECG intervals from the 3 pre-dose time points (45, 30, and 15 minutes before dosing) on Day 1.
Change from Baseline in QRS interval (ΔQRS) was calculated based on a linear mixed-effects model with time (categorical), treatment, and time-by-treatment interaction as fixed effects and Baseline QRS as covariate.
Measured: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.
Part 1: Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval
Continuous 12-lead digital electrocardiogram (ECG) recording was performed on Day 1. ECGs were analyzed at a blinded, central ECG laboratory. At each specified time point, ten 14-second 12-lead ECG tracings were extracted from the continuous recordings. The median QT in each replicate was calculated; the mean of available medians was used as the participant's reportable value at that time point.
QT interval was corrected for heart rate using Fridericia's correction (QTcF). Baseline was defined as the average of the measured ECG intervals from the 3 pre-dose time points (45, 30, and 15 minutes before dosing) on Day 1.
Change from Baseline (ΔQTcF) was calculated based on a linear mixed-effects model with time (categorical), treatment, and time-by-treatment interaction as fixed effects and Baseline QTcF as covariate.
Placebo-corrected ΔQTcF (ΔΔQTcF) was calculated as the adjusted mean ΔQTcF in the S-648414 group minus adjusted mean ΔQTcF in the placebo group at each time point.
Measured: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.
Part 1: Placebo-corrected Change From Baseline in Heart Rate
Continuous 12-lead digital electrocardiogram (ECG) recording was performed on Day 1. ECGs were analyzed at a blinded, central ECG laboratory. At each specified time point, ten 14-second 12-lead ECG tracings were extracted from the continuous recordings. The median HR in each replicate was calculated; the mean of available medians was used as the participant's reportable value at that time point.
Baseline was defined as the average of the measured values from the 3 pre-dose time points (45, 30, and 15 minutes before dosing) on Day 1.
Change from Baseline (ΔHR) was calculated based on a linear mixed-effects model with time (categorical), treatment, and time-by-treatment interaction as fixed effects and Baseline HR as covariate.
Placebo-corrected ΔHR (ΔΔHR) was calculated as the adjusted mean ΔHR in the S-648414 group minus adjusted mean ΔHR in the placebo group at each time point.
Measured: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.
Part 1: Placebo-corrected Change From Baseline in PR Interval
Continuous 12-lead digital electrocardiogram (ECG) recording was performed on Day 1. ECGs were analyzed at a blinded, central ECG laboratory. At each specified time point, ten 14-second 12-lead ECG tracings were extracted from the continuous recordings. The median PR interval in each replicate was calculated; the mean of available medians was used as the participant's reportable value at that time point.
Baseline was defined as the average of the measured ECG intervals from the 3 pre-dose time points (45, 30, and 15 minutes before dosing) on Day 1.
Change from Baseline (ΔPR) was calculated based on a linear mixed-effects model with time (categorical), treatment, and time-by-treatment interaction as fixed effects and Baseline PR as covariate.
Placebo-corrected ΔPR (ΔΔPR) was calculated as the adjusted mean ΔPR in the S-648414 group minus adjusted mean ΔPR in the placebo group at each time point.
Measured: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.
Part 1: Placebo-corrected Change From Baseline in QRS Duration
Continuous 12-lead digital electrocardiogram (ECG) recording was performed on Day 1. ECGs were analyzed at a blinded, central ECG laboratory. At each specified time point, ten 14-second 12-lead ECG tracings were extracted from the continuous recordings. The median QRS duration in each replicate was calculated; the mean of available medians was used as the participant's reportable value at that time point.
Baseline was defined as the average of the measured ECG intervals from the 3 pre-dose time points (45, 30, and 15 minutes before dosing) on Day 1.
Change from Baseline in QRS duration (ΔQRS) was calculated based on a linear mixed-effects model with time (categorical), treatment, and time-by-treatment interaction as fixed effects and Baseline QRS as covariate.
Placebo-corrected ΔQRS (ΔΔQRS) was calculated as the adjusted mean ΔQRS in the S-648414 group minus adjusted mean ΔQRS in the placebo group at each time point.
Measured: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.
Part 1: Number of Participants With Recorded Outlier Values for QTcF, HR, PR, and QRS
A participant was determined as an outlier if the following criteria (assessed separately) were met for the ECG intervals at any time point:
QTcF:
- Treatment-emergent value of > 450 and ≤ 480 ms when not present at Baseline (new onset)
- Treatment-emergent value of > 480 and ≤ 500 ms when not present at Baseline (new onset)
- Treatment-emergent value of > 500 ms when not present at Baseline (new onset)
- Increase of QTcF (ΔQTcF) from Baseline of > 30 and ≤ 60 ms
- Increase of QTcF from Baseline > 60 ms
HR:
- Decrease of HR from Baseline > 25% resulting in HR < 50 bpm
- Increase of HR from Baseline > 25% resulting in HR > 100 bpm
PR:
- Increase of PR from Baseline > 25% resulting in PR > 200 ms
QRS:
- Increase of QRS from Baseline > 25% resulting in QRS > 120 ms
Measured: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.
Part 1: Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence
T-wave abnormalities were categorized as follows:
- Normal T wave: Any positive T wave not meeting any criterion below
- Flat T wave: T amplitude < 1 mm (either positive or negative) including flat isoelectric line
- Notched T wave (+): Presence of notch(es) of at least 0.05 mV amplitude on ascending or descending arm of the positive T wave
- Biphasic: T wave that contains a second component with an opposite phase that is at least 0.1 mV deep (both positive/negative and negative/positive and polyphasic T waves included)
- Normal T wave (-): T amplitude that is negative, without biphasic T wave or notches
- Notched T wave (-): Presence of notch(es) of at least 0.05 mV amplitude on descending or ascending arm of the negative T wave
- U waves: Presence of abnormal U waves
Measured: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2019
- Study start9 Oct 2019
- Primary completion22 Sep 2020
- Study completion29 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Healthy VolunteerStudies of the same condition, open and under way.
- More trials run by ShionogiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shionogi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Shionogi Clinical Trials Administrator Clinical Support Help Line, Study director, Shionogi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04147715
- Sponsor's protocol ID
- 1908T0911
- Status last verified
- Oct 2021
- First submitted
- 28 Oct 2019
- Last updated
- 1 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Randomized, Double-Blind, Single-Ascending-Dose, and Food Effect Study to Assess the Safety, Tolerability, Ventricular Repolarization, and Pharmacokinetics of S-648414 in Healthy Adult Study Participants (Part 1); A Phase 1, Randomized, Double-Blind, Multiple-Ascending-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of S-648414 and A Drug-Drug Interaction Study With the CYP3A Substrate, Midazolam, in Healthy Adult Study Participants (Part 2)
- ClinicalTrials.gov ID
- NCT04147715
- Acronym / sponsor ID
- 1908T0911
- Conditions
- Healthy Volunteer
- Keywords
- Pharmacokinetics, S-648414, Food effect, Antiretroviral, Drug-drug interaction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 98 participants (actual)
- Lead sponsor
- ShionogiIndustry (pharma, biotech, devices)
- Study start
- 9 Oct 2019 (actual)
- Primary completion
- 22 Sep 2020 (actual)
- Study completion
- 29 Sep 2020 (actual)
- First posted
- 1 Nov 2019 (actual)
- Results
- Posted 20 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of Part 1 of the study is to evaluate the safety and tolerability of S-648414 after administration of a single oral dose of S-648414 in healthy adult study participants.
The primary objective of Part 2 is to evaluate the safety and tolerability of S-648414 after administration of multiple oral doses of S-648414 in healthy adult study participants.
The primary objectives of Part 3 are evaluate the safety and tolerability of S-648414 after administration of multiple oral doses of S-648414 in healthy adult study participants, and to evaluate the effect of S-648414 on the pharmacokinetics (PK) of dolutegravir and the effect of dolutegravir on the PK of S-648414 in healthy adult study participants.
Detailed description
Amendment 2 of the study Protocol added a third part (Part 3) to the study. The revised Official Title for the Protocol is:
"A Phase 1, Randomized, Double-Blind, Single-Ascending-Dose, and Food Effect Study to Assess the Safety, Tolerability, Ventricular Repolarization, and Pharmacokinetics of S-648414 in Healthy Adult Study Participants (Part 1); A Phase 1, Randomized, Double-Blind, Multiple-Ascending-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of S-648414 and A Drug-Drug Interaction Study with the CYP3A Substrate, Midazolam, in Healthy Adult Study Participants (Part 2); and A Phase 1 Open-Label Study to Assess the Effect of S-648414 on the Pharmacokinetics of Dolutegravir and the Effect of Dolutegravir on the Pharmacokinetics of S-648414 in Healthy Adult Study Participants (Part 3)"
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Part 1: Placebo | Placebo comparator | Drug: PlaceboParticipants received a single oral dose of matching placebo in a fasted state on Day 1. |
| Part 1: 10 mg S-648414 | Experimental | Drug: S-648414Participants received a single oral dose of 10 mg S-648414 in a fasted state on Day 1. |
| Part 1: 30 mg S-648414 | Experimental | Drug: S-648414Participants received a single oral dose of 30 mg S-648414 in a fasted state on Day 1. |
| Part 1: 100 mg S-648414 | Experimental | Drug: S-648414Participants received a single oral dose of 100 mg S-648414 in a fasted state on Day 1 followed by a single dose of S-648414 in a fed state (after a high-fat meal) on Day 14. |
| Part 1: 250 mg S-648414 | Experimental | Drug: S-648414Participants received a single oral dose of 250 mg S-648414 in a fasted state on Day 1. |
| Part 1: 500 mg S-648414 | Experimental | Drug: S-648414Participants received a single oral dose of 500 mg S-648414 in a fasted state on Day 1. |
| Part 1: 1000 mg S-648414 | Experimental | Drug: S-648414Participants received a single oral dose of 1000 mg S-648414 in a fasted state on Day 1. |
| Part 2: Placebo + Midazolam | Placebo comparator | Drug: Placebo, Drug: MidazolamParticipants received matching placebo once a day on Days 1 to 14 and a single oral dose of 5 mg midazolam alone on Day -2 and co-administered with the placebo dose on Day 14. |
| Part 2: 50 mg S-648414 + Midazolam | Experimental | Drug: S-648414, Drug: MidazolamParticipants received 50 mg S-648414 once a day on Days 1 to 14 and a single oral dose of 5 mg midazolam alone on Day -2 and co-administered with the S-648414 dose on Day 14. |
| Part 2: 30 mg S-648414 + Midazolam | Experimental | Drug: S-648414, Drug: MidazolamParticipants received 30 mg S-648414 once a day on Days 1 to 14 and a single oral dose of 5 mg midazolam alone on Day -2 and co-administered with the S-648414 dose on Day 14. |
| Part 3: 100 mg S-648414 + Dolutegravir | Experimental | Drug: S-648414, Drug: DolutegravirParticipants received 50 mg dolutegravir orally once a day on Days 1 to 7, 100 mg S-648414 orally once a day on Days 15 to 21, and 50 mg dolutegravir co-administered with 100 mg S-648414 orally once a day on Days 22 to 28. |
| Part 3: 200 mg S-648414 + Dolutegravir | Experimental | Drug: S-648414, Drug: DolutegravirParticipants received 50 mg dolutegravir orally once a day on Days 1 to 7, 200 mg S-648414 orally once a day on Days 15 to 21, and 50 mg dolutegravir co-administered with 200 mg S-648414 orally once a day on Days 22 to 28. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Male or female adults ≥ 18 years in USA or ≥ 20 years in Japan to ≤ 55 years of age, at the time of signing the informed consent form (ICF).
- Capable of giving signed informed consent
- Body mass index (BMI) ≥ 18.5 to < 32.0 kg/m² at the Screening visit．
- Considered medically healthy as determined by the investigator or subinvestigator (suitably qualified), based on medical history and clinical evaluations including physical examination, clinical laboratory tests, vital sign measurements, and 12-lead electrocardiogram (ECG) at Screening and at upon admission to the Clinical Research Unit (CRU) and prior to administration of study intervention on Day 1.
- Female study participants must not be a woman of childbearing potential and must either be postmenopausal (defined as no menses for 12 months without an alternative medical cause; follicle-stimulating hormone (FSH) to be tested for confirmation at Screening) or premenopausal with 1 of the following documented: hysterectomy, tubal ligation, bilateral salpingectomy, or bilateral oophorectomy.
Key exclusion criteria (26 listed)
- Considered by the investigator or subinvestigator (suitably qualified) to be ineligible for the study due to a history of or current condition of significant metabolic or endocrine, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal (GI), urological, immunological, neurological, or psychiatric disorders with clinical manifestations.
- History or presence of cancer in last 5 years except for non-melanoma skin cancers.
- Risk factors for:
- History of GI surgery or disease including, but not limited to, gastric band/gastric resection and/or intestinal resection and/or duodenal disease (ie, celiac disease) that may result in clinically significant malabsorption (except for an appendectomy).
- History of hypersensitivity or severe side effects induced by a drug.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| S-648414Tablet for oral administration | Drug | Part 1: 10 mg S-648414, Part 1: 100 mg S-648414, Part 1: 1000 mg S-648414, Part 1: 250 mg S-648414, Part 1: 30 mg S-648414, Part 1: 500 mg S-648414, Part 2: 30 mg S-648414 + Midazolam, Part 2: 50 mg S-648414 + Midazolam, Part 3: 100 mg S-648414 + Dolutegravir, Part 3: 200 mg S-648414 + Dolutegravir |
| PlaceboTablet for oral administration | Drug | Part 1: Placebo, Part 2: Placebo + Midazolam |
| MidazolamAlso: VersedSolution for oral administration | Drug | Part 2: 30 mg S-648414 + Midazolam, Part 2: 50 mg S-648414 + Midazolam, Part 2: Placebo + Midazolam |
| DolutegravirAlso: TIVICAYTablet for oral administration | Drug | Part 3: 100 mg S-648414 + Dolutegravir, Part 3: 200 mg S-648414 + Dolutegravir |
Primary outcome
Part 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: From dosing on Day 1 or Day 14 up to 10 days post dose
A TEAE is any event not present before exposure to study drug or any event already present that worsens after exposure to study drug. A serious adverse event is any untoward medical occurrence that resulted in death, was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or other event that may have jeopardized the participant or required intervention to prevent one of the outcomes above. The investigator assessed the intensity of each AE according to the following: Grade 1 (Mild): No or minimal interference with usual activities. Grade 2 (Moderate): More than minimal interference with usual activities, intervention indicated. Grade 3 (Severe): Inability to perform usual activities, intervention or hospitalization indicated. Grade 4 (Potentially life-threatening): Inability to perform self-care, intervention indicated to prevent permanent impairment, disability, or death.
Part 2: Number of Participants With Treatment-emergent Adverse Events
Time frame: From the first dose up to 10 days after end of dosing (25 days); A TEAE was summarized to a given treatment if the event onset/worsening occurred any time after the dose of that treatment and before the dose of the next treatment.
A TEAE is any event not present before exposure to study drug or any event already present that worsens after exposure to study drug. A serious adverse event is any untoward medical occurrence that resulted in death, was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or other event that may have jeopardized the participant or required intervention to prevent one of the outcomes above. The investigator assessed the intensity of each AE according to the following: Grade 1 (Mild): No or minimal interference with usual activities. Grade 2 (Moderate): More than minimal interference with usual activities, intervention indicated. Grade 3 (Severe): Inability to perform usual activities, intervention or hospitalization indicated. Grade 4 (Potentially life-threatening): Inability to perform self-care, intervention indicated to prevent permanent impairment, disability, or death.
Part 3: Number of Participants With Treatment-emergent Adverse Events
Time frame: From the first dose up to Day 36; A TEAE was summarized to a given treatment if the event onset/worsening occurred any time after the dose of that treatment and before the dose of the next treatment.
A TEAE is any event not present before exposure to study drug or any event already present that worsens after exposure to study drug. A serious adverse event is any untoward medical occurrence that resulted in death, was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or other event that may have jeopardized the participant or required intervention to prevent one of the outcomes above. The investigator assessed the intensity of each AE according to the following: Grade 1 (Mild): No or minimal interference with usual activities. Grade 2 (Moderate): More than minimal interference with usual activities, intervention indicated. Grade 3 (Severe): Inability to perform usual activities, intervention or hospitalization indicated. Grade 4 (Potentially life-threatening): Inability to perform self-care, intervention indicated to prevent permanent impairment, disability, or death.
Part 3: Maximum Plasma Concentration (Cmax) of S-648414
Time frame: Day 21 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose. Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
The effect of dolutegravir on the pharmacokinetics (PK) of S-648414 was assessed after administration of multiple oral doses of S-648414 alone (Day 21) and after administration of multiple oral doses of S-648414 co-administered with dolutegravir (Day 28).
Part 3: Time to Maximum Plasma Concentration (Tmax) of S-648414
Time frame: Day 21 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose. Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
The effect of dolutegravir on the pharmacokinetics (PK) of S-648414 was assessed after administration of multiple oral doses of S-648414 alone (Day 21) and after administration of multiple oral doses of S-648414 co-administered with dolutegravir (Day 28).
Part 3: Plasma Concentration of S-648414 at the End of the Dosing Interval τ (Cτ)
Time frame: Day 22 and Day 29 (24 hours post-dosing on Days 21 and 28)
The effect of dolutegravir on the pharmacokinetics (PK) of S-648414 was assessed after administration of multiple oral doses of S-648414 alone (Day 21) and after administration of multiple oral doses of S-648414 co-administered with dolutegravir (Day 28).
Part 3: Area Under the Concentration-time Curve Over the Dosing Interval τ (AUC0-τ) for S-648414
Time frame: Day 21 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose. Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
The effect of dolutegravir on the pharmacokinetics (PK) of S-648414 was assessed after administration of multiple oral doses of S-648414 alone (Day 21) and after administration of multiple oral doses of S-648414 co-administered with dolutegravir (Day 28). Area under the concentration-time curve over the dosing interval τ (24 hours) was calculated by the linear up/log down trapezoidal method.
Part 3: Apparent Total Clearance (CL/F) of S-648414
Time frame: Day 21 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose. Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
The effect of dolutegravir on the pharmacokinetics (PK) of S-648414 was assessed after administration of multiple oral doses of S-648414 alone (Day 21) and after administration of multiple oral doses of S-648414 co-administered with dolutegravir (Day 28). Apparent total clearance was calculated as CL/F = Dose/AUC0-τ
Part 3: Maximum Plasma Concentration (Cmax) of Dolutegravir
Time frame: Day 7 and Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours postdose.
The effect of S-648414 on the PK of dolutegravir was assessed after administration of multiple oral doses of dolutegravir alone and after administration of multiple oral doses of S-648414 co-administered with dolutegravir.
Part 3: Time to Maximum Plasma Concentration (Tmax) of Dolutegravir
Time frame: Day 7 and Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours postdose.
The effect of S-648414 on the PK of dolutegravir was assessed after administration of multiple oral doses of dolutegravir alone and after administration of multiple oral doses of S-648414 co-administered with dolutegravir.
Part 3: Plasma Concentration of Dolutegravir at the End of the Dosing Interval τ (Cτ)
Time frame: Day 8 and Day 29 (24 hours post-dosing on Day 7 and Day 28).
The effect of S-648414 on the PK of dolutegravir was assessed after administration of multiple oral doses of dolutegravir alone and after administration of multiple oral doses of S-648414 co-administered with dolutegravir.
Part 3: Area Under the Concentration-time Curve Over the Dosing Interval τ (AUC0-τ) for Dolutegravir
Time frame: Day 7 and Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours postdose.
The effect of S-648414 on the PK of dolutegravir was assessed after administration of multiple oral doses of dolutegravir alone and after administration of multiple oral doses of S-648414 co-administered with dolutegravir. Area under the concentration-time curve over the dosing interval τ (24 hours) was calculated by the linear up/log down trapezoidal method.
Part 3: Apparent Total Clearance (CL/F) of Dolutegravir
Time frame: Day 7 and Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours postdose.
The effect of S-648414 on the PK of dolutegravir was assessed after administration of multiple oral doses of dolutegravir alone and after administration of multiple oral doses of S-648414 co-administered with dolutegravir. Apparent total clearance calculated as CL/F =Dose/AUC0-τ
37 secondary outcomes
Part 1: Maximum Plasma Concentration (Cmax) of S-648414
Time frame: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.
Part 1: Time to Maximum Plasma Concentration (Tmax) of S-648414
Time frame: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.
Part 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration After Dosing (AUC0-last) of S-648414
Time frame: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.
Part 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of S-648414
Time frame: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.
Part 1: Terminal Elimination Half-life (t1/2,z) of S-648414
Time frame: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.
Part 1: Terminal Elimination Rate Constant (λz) of S-648414
Time frame: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.
Part 1: Mean Residence Time (MRT) of S-648414
Time frame: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.
Part 1: Apparent Total Clearance (CL/F) of S-648414
Time frame: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.
Part 1: Apparent Volume of Distribution in the Terminal Elimination Phase (Vz/F) of S-648414
Time frame: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.
Part 1: Fraction of S-648414 Dose Excreted in Urine From 0 to 96 Hours Postdose (Feu0-96)
Time frame: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose (-12 to 0 hours), 0 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours postdose
Part 1: Renal Clearance (CLR) of S-648414
Time frame: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose (-12 to 0 hours), 0 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours postdose
Part 2: Maximum Plasma Concentration (Cmax) of S-648414 Following Single and Multiple-dose Administration
Time frame: Day 1 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose; Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96 hours postdose.
Part 2: Time to Maximum Plasma Concentration (Tmax) of S-648414 Following Single and Multiple-dose Administration
Time frame: Day 1 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose; Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96 hours postdose.
Part 2: Area Under the Concentration-time Curve Over the Dosing Interval τ (AUC0-τ) of S-648414 Following Single and Multiple-dose Administration
Time frame: Day 1 and day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 2: Terminal Elimination Half-life (t1/2,z) of S-648414 Following Multiple-dose Administration
Time frame: Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96 hours postdose.
Part 2: Terminal Elimination Rate Constant (λz) of S-648414 Following Multiple-dose Administration
Time frame: Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96 hours postdose.
Part 2: Apparent Total Clearance (CL/F) of S-648414 Following Multiple-dose Administration
Time frame: Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 2: Apparent Volume of Distribution in the Terminal Elimination Phase (Vz/F) of S-648414 Following Multiple-dose Administration
Time frame: Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96 hours postdose.
Part 2: Fraction of S-648414 Dose Excreted in Urine Over the Dosing Interval (Feu0- τ) Following Multiple-dose Administration
Time frame: Day 14 0-24 hours postdose
Part 2: Renal Clearance (CLR) of S-648414 Following Multiple-dose Administration
Time frame: Day 14 0-24 hours postdose
Part 2: Maximum Plasma Concentration (Cmax) of Midazolam
Time frame: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 2: Time to Maximum Plasma Concentration of Midazolam
Time frame: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 2: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration After Dosing (AUC0-last) for Midazolam
Time frame: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 2: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Midazolam
Time frame: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 2: Terminal Elimination Half-life for Midazolam
Time frame: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 2: Terminal Elimination Rate Constant for Midazolam
Time frame: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 2: Mean Residence Time for Midazolam
Time frame: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.
Part 1: Change From Baseline in Fridericia's Corrected QT Interval (QTcF)
Time frame: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.
Parts 1: Change From Baseline in Heart Rate (HR)
Time frame: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.
Part 1: Change From Baseline in PR Interval
Time frame: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.
Part 1: Change From Baseline in QRS Interval
Time frame: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.
Part 1: Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval
Time frame: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.
Part 1: Placebo-corrected Change From Baseline in Heart Rate
Time frame: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.
Part 1: Placebo-corrected Change From Baseline in PR Interval
Time frame: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.
Part 1: Placebo-corrected Change From Baseline in QRS Duration
Time frame: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.
Part 1: Number of Participants With Recorded Outlier Values for QTcF, HR, PR, and QRS
Time frame: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.
Part 1: Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence
Time frame: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shionogi Clinical Trials Administrator Clinical Support Help Line study director
Shionogi
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing S-648414, Midazolam and Dolutegravir in people with Healthy Volunteer, run by Shionogi at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) (time frame: From dosing on Day 1 or Day 14 up to 10 days post dose). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2021.