Autoimmune DiseasesPhase 1NCT03305419
A Safety and Pharmacokinetic (PK) Study of GSK2982772 in Healthy Subjects
A Phase 1 study testing GSK2982772 capsule in people with Autoimmune Diseases, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial summary
This study is designed to evaluate the safety, tolerability and PK of GSK2982772, in repeat oral doses in healthy subjects. This study is being conducted to support administration of higher dose levels of GSK2982772 than initially studied in the First Time in Human (FTiH) study. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Autoimmune Diseases
- What is being tested?
- GSK2982772 capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 11 Oct 2017to 15 Oct 2018
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
- Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, neurological examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator in consultation with the Medical Monitor (if required) agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Body weight >=50 kilograms (kg) and body mass index (BMI) within the range 19 - 30 kg per square meter (kg/m^2) (inclusive).
- A male subject with a female partner of reproductive potential must agree to use contraception during the treatment period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance for a minimum of 28 days prior to the treatment period and for at least 30 days after the last administration of study drug. A WOCBP using a hormonal method of highly effective contraception must also agree to partner use of a male condom during the treatment period and for at least 30 days after the last administration of study drug.
- Capable of giving signed informed consent.
Who cannot join
- History or presence of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
- History of herpes zoster (shingles) reactivation.
- Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest x-rays (posterior anterior and lateral), and TB testing: either a positive tuberculin skin test (TST; defined as a skin induration >5 millimeter (mm) at 48 to 72 hours, regardless of Bacillus Calmette-Guerin (BCG) or other vaccination history) or a positive (not indeterminate) QuantiFERON-TB Gold test.
- ALT >1.5 times upper limit of normal (ULN).
- Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
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- ECG QT interval corrected for heart rate (QTc) >450 millisecond (msec).
- History of serious or recurrent infections or has had an active infection within 14 days of receiving study medication.
- History of diagnosis of obstructive sleep apnoea or significant respiratory disorder. Childhood asthma that has fully resolved is permitted.
- Part A: History of active suicidal ideation behavior (SIB) within the past 6 months or any history of attempted suicide in a subject's lifetime.
- History of current evidence of febrile seizures, epilepsy, convulsions, significant head injury, or other significant neurologic conditions.
- Past or intended use of over-the-counter or prescription medication, including herbal medications, within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is the longest) prior to dosing.
- Subject received a vaccine (either live attenuated or now-live) within 30 days prior to randomization, or plans to receive a live attenuated vaccine within 30 days + 5 half-lives (32 days) of the last dose of study medication.
- Participation in the study would result in loss of blood or blood products in excess of 500 milliliters (mL) within a 56-day period.
- Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Presence of Hepatitis B surface antigen (HBsAg) at screening Positive Hepatitis C antibody test result at screening.
- Positive pre-study drug/alcohol screen.
- Positive human immunodeficiency virus (HIV1 and 2) antibody test.
- Regular use of known drugs of abuse.
- Subjects with impaired renal function defined as Chronic Kidney Disease Epidemiology Collaboration (CKS-EPI) Creatinine > 1.6 mg/deciliter (mg/dL) with an age appropriate glomerular filtration rate (GFR) <= 60 (mL/minute/1.73 m^2) estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
- An elevated C-reactive protein (CRP) outside of the normal reference range.
- Regular alcohol consumption within 6 months prior to the study defined as: For United Kingdom (UK) - an average weekly intake of >14 units for males and females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
- Cotinine or carbon monoxide levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
- Unwilling or unable to swallow multiple size 00 capsules as part of study participation.
- PART B Specific exclusion criteria:
- History of SIB as measured using the Columbia Suicide Severity Rating Scale (C-SSRS) or a history of attempted suicide.
- A positive anti-nuclear antibody (ANA) outside of the normal reference range.
- Fasting total cholesterol >=300 mg/dL or triglycerides >=250 mg/dL.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single-centre, Randomized, Double-blind (Sponsor-unblinded), Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK2982772 in Repeat Oral Doses in Healthy Subjects
This study is designed to evaluate the safety, tolerability and PK of GSK2982772, in repeat oral doses in healthy subjects. This study is being conducted to support administration of higher dose levels of GSK2982772 than initially studied in the First Time in Human (FTiH) study. This study will also assess the impact of food during the repeat doses of GSK2982772. This will be a two part study; Part A and Part B. Part A (cohort 1) - single ascending dose, randomized, placebo-controlled, 3-way crossover. Part B (cohorts 2, 3, 4 and 5) - repeat dose, randomized, placebo-controlled, sequential-group. Subjects will be randomized in 3:1 ratio to receive GSK2982772 or placebo in crossover manner on Day 1 of each of the three periods in Part A. Subjects will be randomized in 3:1 ratio to receive GSK2982772 or placebo in sequential groups for 14 days in cohort 2 of Part B and in 9:5 ratio to receive GSK2982772 or placebo in sequential groups for 14 days in cohorts 3, 4 and 5 of Part B. Approximately 66 subjects will be included in this study. The study duration, including screening and follow-up, will not be expected to exceed 13 weeks for Part A and 8 weeks for Part B.
- Conditions
- Autoimmune Diseases
- Being tested
- GSK2982772 capsule, Placebo capsule
- Keywords
- Crossover, Sequential, GSK2982772, Safety, Pharmacokinetics, Healthy subjects
- Medical subject headings
- Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2982772 capsuleDrug
GSK2982772 will be available as size 00, white, opaque capsule containing white to almost white Solid (120 mg maximum fill per capsule). It will be administered orally with water to receive total dose of 120 mg, 240 mg or 360 mg per randomization.
Placebo capsuleDrug
Placebo will be available as size 00, white, opaque capsule containing white to almost white Solid. It will be administered orally with water.
| Study group | Role | What they receive |
|---|---|---|
| Subjects receiving treatment sequence ABC in cohort 1: Part A | Experimental | Eligible subjects will be randomized to receive treatment sequence ABC in Part A; A= GSK2982772 120 mg TID, B= GSK2982772 240 mg TID, and C= GSK2982772 360 mg BID. Subjects will receive oral capsule of GSK2982772 or placebo on Day 1 in each of the 3 treatment periods followed by a wash-out period of at least 7 days between dosing regimens. Receives: Drug: GSK2982772 capsule; Drug: Placebo capsule |
| Subjects receiving treatment sequence ABP in cohort 1: Part A | Experimental | Eligible subjects will be randomized to receive treatment sequence ABP in Part A; A= GSK2982772 120 mg TID, B= GSK2982772 240 mg TID, and P= Placebo. Subjects will receive oral capsule of GSK2982772 or placebo on Day 1 in each of the 3 treatment periods followed by a wash-out period of at least 7 days between dosing regimens. Receives: Drug: GSK2982772 capsule; Drug: Placebo capsule |
| Subjects receiving treatment sequence APC in cohort 1: Part A | Experimental | Eligible subjects will be randomized to receive treatment sequence APC in Part A; A= GSK2982772 120 mg TID, P= Placebo and C= GSK2982772 360 mg BID. Subjects will receive oral capsule of GSK2982772 or placebo on Day 1 in each of the 3 treatment periods followed by a wash-out period of at least 7 days between dosing regimens. Receives: Drug: GSK2982772 capsule; Drug: Placebo capsule |
| Subjects receiving treatment sequence PBC in cohort 1: Part A | Experimental | Eligible subjects will be randomized to receive treatment sequence PBC in Part A; P= Placebo, B= GSK2982772 240 mg TID and C= GSK2982772 360 mg BID. Subjects will receive oral capsule of GSK2982772 or placebo on Day 1 in each of the 3 treatment periods followed by a wash-out period of at least 7 days between dosing regimens. Receives: Drug: GSK2982772 capsule; Drug: Placebo capsule |
| Subjects receiving GSK2982772 120 mg TID in cohort 2 : Part B | Experimental | Eligible subjects will receive GSK2982772 oral capsule with a dose of 120 mg TID for 14 days in Part B. Receives: Drug: GSK2982772 capsule |
| Subjects receiving GSK2982772 120 mg TID in cohort 3 : Part B | Experimental | Eligible subjects will receive GSK2982772 oral capsule with a dose of 120 mg TID for 14 days in Part B. Receives: Drug: GSK2982772 capsule |
| Subjects receiving GSK2982772 240 mg TID in cohort 4: Part B | Experimental | Eligible subjects will receive GSK2982772 oral capsule with a dose of 240 mg TID for 14 days in Part B. Receives: Drug: GSK2982772 capsule |
| Subjects receiving GSK2982772 360 mg BID in cohort 5: Part B | Experimental | Eligible subjects will receive GSK2982772 oral capsule with a dose of 360 mg BID for 14 days in Part B. Receives: Drug: GSK2982772 capsule |
| Subjects receiving placebo in cohort 2 : Part B | Placebo comparator | Subjects will receive placebo oral capsule for 14 days in Part B. Receives: Drug: Placebo capsule |
| Subjects receiving placebo in cohort 3 : Part B | Placebo comparator | Subjects will receive placebo oral capsule for 14 days in Part B. Receives: Drug: Placebo capsule |
| Subjects receiving placebo in cohort 4 : Part B | Placebo comparator | Subjects will receive placebo oral capsule for 14 days in Part B. Receives: Drug: Placebo capsule |
| Subjects receiving placebo in cohort 5: Part B | Placebo comparator | Subjects will receive placebo oral capsule for 14 days in Part B. Receives: Drug: Placebo capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Adverse Events (AEs) and Serious AEs (SAEs): Part A
An AE is any untoward medical occurrence in a clinical study subjects, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.
Measured: Up to Day 14
Number of Participants With AEs and SAEs: Part B
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE.
Measured: Up to Day 28
Number of Participants With Worst Case Clinical Chemistry Parameters by Potential Clinical Importance Criteria: Part A
Blood samples were collected from participants for the analysis of following clinical chemistry parameters: alanine amino transferase (ALT), albumin, alkaline phosphatase, aspartate amino transferase (AST), calcium, creatinine, glucose, potassium, sodium and total bilirubin. PCI ranges were >=2 times Upper Limit of Normal (ULN) units per liter (U/L) for ALT, <30 grams per liter (g/L) for albumin, >=2 times ULN U/L for alkaline phosphatase, >=2 times ULN U/L for AST, <2 or >2.75 millimoles per liter (mmol/L) for calcium, >44.2 micromoles per liter (µmol/L) for creatinine, <3 or >9 mmol/L for glucose, <3 or >5.5 mmol/L for potassium, <130 or >150 mmol/L for sodium and >=1.5 times ULN for total bilirubin. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.
Measured: Up to Week 9
Number of Participants With Worst Case Clinical Chemistry Parameters by Potential Clinical Importance Criteria: Part B
Blood samples were collected from participants for the analysis of following clinical chemistry parameters: ALT, albumin, alkaline phosphatase, AST, calcium, creatinine, glucose, potassium, sodium and total bilirubin. PCI ranges were >=2 times ULN U/L for ALT, <30 g/L for albumin, >=2 times ULN U/L for alkaline phosphatase, >=2 times ULN U/L for AST, <2 or >2.75 mmol/L for calcium, >44.2 µmol/L for creatinine, <3 or >9 mmol/L for glucose, <3 or >5.5 mmol/L for potassium, <130 or >150 mmol/L for sodium and >=1.5 times ULN for total bilirubin. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.
Measured: Up to Week 4
Number of Participants With Worst Case Hematology Parameters by Potential Clinical Importance Criteria: Part A
Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, lymphocytes, platelet count, total neutrophils and white blood cell (WBC) counts. PCI ranges were >0.54 or < 0.075 proportion of red blood cells (RBC) in blood for hematocrit, <25 or >180 g/L for hemoglobin, 0.8 x10^9 cells/L for lymphocytes, <1.5 x10^9 cells/L for neutrophils, <100 or >550 x10^9 cells/L for platelets and <3 or 20> x 10^9 cells per liter WBC. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.
Measured: Up to Week 9
Number of Participants With Worst Case Hematology Parameters by Potential Clinical Importance Criteria: Part B
Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, lymphocytes, platelet count, total neutrophils and WBC counts. PCI ranges were >0.54 or < 0.075 proportion of RBC in blood for hematocrit, <25 or >180 g/L for hemoglobin, 0.8 x10^9 cells/L for lymphocytes, <1.5 x10^9 cells/L for neutrophils, <100 or >550 x10^9 cells/L for platelets and <3 or 20> x 10^9 cells per liter WBC. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.
Measured: Up to Week 4
Number of Participants With Worst Case Urinalysis Results: Part A
Urine samples were collected from participants for analysis of following parameters: cellular casts, granular casts, hyaline casts, RBC and WBC and were counted as cells per high-power field (cells/HPF). The number of participants with cells in urine has been presented.
Measured: Up to Week 9
Number of Participants With Worst Case Urinalysis Results: Part B
Urine samples were collected from participants for analysis of following parameters: cellular casts, granular casts, hyaline casts, RBC and WBC and were counted as cells per high-power field (cells/HPF). The number of participants with cells in urine has been presented.
Measured: Up to Week 4
Number of Participants With Abnormal Vital Signs: Part A
Vital signs were measured in a supine position after 5 minutes rest. The PCI criteria for vital signs included: systolic blood pressure <85 and >160 millimeters of mercury [mmHg]), diastolic blood pressure <45 mmHg and >100 mmHg, heart rate <40 and >100 beats per minute, body temperature <=35.5 and >=37.8 degrees Celsius and respiration rate <=8 and >=20 breaths per minute. Data of participants with potential clinical importance has been reported.
Measured: Up to Week 9
Number of Participants With Abnormal Vital Signs: Part B
Vital signs were measured in a supine position after 5 minutes rest. The PCI criteria for vital signs included: systolic blood pressure <85 and >160 mmHg, diastolic blood pressure <45 mmHg and >100 mmHg, heart rate <40 and >100 beats per minute, body temperature <=35.5 and >=37.8 degrees Celsius and respiration rate <=8 and >=20 breaths per minute. Data of participants with potential clinical importance has been reported.
Measured: Up to Week 4
Number of Participants With Abnormal Electrocardiogram (ECG) Findings: Part A
12-lead ECG's were obtained in the supine position after 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Measured: Up to Day 4
Number of Participants With Abnormal ECG Findings: Part B
12-lead ECG's were obtained in the supine position after 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Measured: Up to Week 4
Secondary outcomes (40)
Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours (AUC[0-24]) Following TID Dosing of GSK2982772: Part A
Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 20, 40minutes, 1 hour, 1hr 30min, 2, 3, 5, 7hour, 7hr 20min,and 7hr 40 min, 8hr, 8hr 30min, 9hr, 10hr, 12hr, 14hr, 14hr 20min, 14hr 40 min, 15hr, 15hr 30min, 16hr, 17hr, 19hr, 22hr, 24hours post dose on Day1
AUC(0-24) Following BID Dosing of GSK2982772: Part A
Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 20min, 40min, 1hr, 1hr 30min, 2hr, 3hr, 4hr, 6hr, 8hr, 10hr, 12hr, 12hr 20min, 12hr 40min, 13hr, 13hr 30min, 14hr, 15hr, 16hr, 19hr, 22hr, 24hr post dose on Day 1.
AUC[0-24] Following TID Dosing of GSK2982772: Part B
Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 20, 40minutes, 1 hour, 1hr 30min, 2, 3, 5, 7hour, 7hr 20min,and 7hr 40 min, 8hr, 8hr 30min, 9hr, 10hr, 12hr, 14hr, 14hr 20min, 14hr 40 min, 15hr, 15hr 30min, 16hr, 17hr, 19hr, 22hr, 24hours post dose on Day14
AUC (0-7) Following TID Dosing of GSK2982772 : Part A
Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Day 1
AUC (7-14) Following TID Dosing of GSK2982772 : Part A
Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 7 hours, 7 hours 20 and 40 minutes, 8 hours, 8 hours 30 minutes, 9, 10, 12, 14 hours on Day 1
AUC (14-24) Following TID Dosing of GSK2982772 : Part A
Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 14 hours, 14 hours 20 and 40 minutes, 15 hours ,15 hours 30 minutes, 16, 19, 22 and 24 hours on Day 1
AUC (0-12) Following BID Dosing of GSK2982772 in Part A
Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 4, 6, 8, 10 hours,12 hours on Day 1
AUC (12-24) Following BID Dosing of GSK2982772 in Part A
Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 12 hours, 12 hours 20 and 40 minutes, 13 and 13 hours 30 minutes, 14, 15, 16, 19, 22 and 24 hours on Day 1
AUC(0-7) Following TID Dosing of GSK2982772 in Part B
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Days 1 and 14
AUC (7-14) Following TID Dosing of GSK2982772 in Part B
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 7 and 7 hours 20 and 40 minutes, 8 and 8 hours 30 minutes, 9, 10, 12, 14 hours on Day 14
AUC (14-24) Following TID Dosing of GSK2982772 in Part B
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 14 hours, 14 hours 20 minutes, 14 hours 40 minutes, 15 hours, 15 hours 30 minutes, 16, 17, 19, 22 and 24 hours on Day 14
Maximum Observed Plasma Drug Concentration Cmax (0-7) Following TID Dosing of GSK2982772 in Part A
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, and 7 hours post dose on Day 1
Cmax (7-14) Following TID Dosing of GSK2982772 in Part A
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 7 hours, 7 hours 20 and 40 minutes, 8 and 8 hours 30 minutes, 9, 10, 12, 14 hours post dose on Day 1
Cmax (14-24) Following TID Dosing of GSK2982772 in Part A
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 14 hours, 14 hours 20 and 40 minutes, 15 and 15 hours 30 minutes, 16, 19, 22 and 24 hours post dose on Day 1
Cmax (0-12) Following BID Dosing of GSK2982772 in Part A
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 4, 6, 8, 10 hours and 12 hours post dose on Day 1
Cmax (12-24) Following BID Dosing of GSK2982772 in Part A
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 12 hours, 12 hours 20 and 40 minutes, 13 and 13 hours 30 minutes, 14, 15, 16, 19, 22 and 24 hours post dose on Day 1
Cmax (0-7) Following TID Dosing of GSK2982772 in Part B
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours post dose on Days 1 and 14
Cmax (7-14) Following TID Dosing of GSK2982772 in Part B
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 7hours, 7 hours 20 and 40 minutes, 8 hours, 8 hours 30 minutes, 9, 10, 12, 14 hours on Day 14
Cmax (14-24) Following TID Dosing of GSK2982772 in Part B
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 14 hours, 14 hours 20 and 40 minutes, 15 hours, 15 hours 30 minutes, 16, 17, 19, 22 and 24 hours post dose on Day 14
Time to Cmax (Tmax) (0-7) Following TID Dosing of GSK2982772 in Part A
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, and 7 hours post dose on Day 1
Tmax (7-14) Following TID Dosing of GSK2982772 in Part A
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 7hours, 7 hours 20 and 40 minutes, 8 hours, 8 hours 30 minutes, 9, 10, 12, 14 hours post dose on Day 1
Tmax (14-24) Following TID Dosing of GSK2982772 in Part A
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 14 hours, 14 hours 20 and 40 minutes, 15 hours, 15 hours 30 minutes, 16, 17, 19, 22 and 24 hours post dose on Day 1
Tmax (0-12) Following BID Dosing of GSK2982772 in Part A
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 20 and 40 minutes, 1hour, 1 hour 30 minutes, 2, 3, 4, 6, 8, 10 hours and 12 hours post dose on Day 1
Tmax (12-24) Following BID Dosing of GSK2982772 in Part A
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 12 hours, 12 hours 20 and 40 minutes, 13 hours, 13 hours 30 minutes, 14, 15, 16, 19, 22 and 24 hours post dose on Day 1
Tmax (0-7) Following TID Dosing of GSK2982772 Part B
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 20 and 40 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 5, 7 hours post dose on Days 1 and 14
Tmax (7-14) Following TID Dosing of GSK2982772 in Part B
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 7hours and 7 hours 20 and 40 minutes, 8hours, 8 hours 30 minutes, 9, 10, 12, 14 hours post dose on Day 14
Tmax (14-24) Following TID Dosing of GSK2982772 in Part B
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 14hours, 14 hours 20 and 40 minutes, 15 hours and 15 hours 30 minutes, 16, 17, 19, 22 and 24 hours post dose on Day 14
Observed Trough Plasma Drug Concentration at 7 Hour (C7),Following TID Dosing of GSK2982772 in Part A
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 7 hours post-dose on Day 1
Observed Trough Plasma Drug Concentration at 14 Hours (C14) Following TID Dosing of GSK2982772 in Part A
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 14 hours post-dose on Day 1
C24 Following TID Dosing of GSK2982772 in Part A
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 24 hours post-dose on Day 1
C12 Following BID Dosing of GSK2982772 in Part A
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 12 hours post-dose on Day 1
C24 Following BID Dosing of GSK2982772 in Part A
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 24 hours post-dose on Day 1
C0 Following TID Dosing of GSK2982772 in Part B
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose on Day 14
C7 Following TID Dosing of GSK2982772 in Part B
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 7 hours post-dose on Days 1 and 14
C14 Following TID Dosing of GSK2982772 in Part B
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 14 hours post-dose on Day 14
C24 Following TID Dosing of GSK2982772 in Part B
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: 24 hours post-dose on Day 14
AUC([0-7] Following TID Dosing of GSK2982772 in Fed State of Part B
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Days 9 and 11
Cmax (0-7) Following TID Dosing of GSK2982772 in Fed State of Part B
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Days 9 and 11
Tmax (0-7) Following TID Dosing of GSK2982772 in Fed State of Part B
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Days 9 and 11
Ratio of Plasma 4 Beta-hydroxycholesterol to Cholesterol: Part B
Blood samples were collected into EDTA tubes and processed to plasma for 4 beta-hydroxycholesterol and cholesterol. Ratio of 4 beta-hydroxycholesterol to cholesterol is presented
Measured: Pre-dose on Day 1 and 24 hours post first dose on Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2017
- Study start11 Oct 2017
- Primary completion15 Oct 2018
- Study completion15 Oct 2018
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Autoimmune DiseasesStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe 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
- Model description
- This study will consist of two parts; Part A and Part B. Part A will be a 3-way crossover design and Part B will be a sequential-group design.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03305419
- Sponsor's protocol ID
- 205184
- Other IDs
- 2017-002662-45, 2017
- Status last verified
- Sep 2023
- First submitted
- 4 Oct 2017
- Last updated
- 10 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
Publications
Tompson DJ, Davies C, Scott NE, Cannons EP, Kostapanos M, Gross AS, Powell M, Ino H, Shimamura R, Ogura H, Nagakubo T, Igarashi H, Nakano A. Comparison of the Pharmacokinetics of RIPK1 Inhibitor GSK2982772 in Healthy Western and Japanese Subjects. Eur J Drug Metab Pharmacokinet. 2021 Jan;46(1):71-83. doi: 10.1007/s13318-020-00652-2.
PubMed 33165774
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-centre, Randomized, Double-blind (Sponsor-unblinded), Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK2982772 in Repeat Oral Doses in Healthy Subjects
- ClinicalTrials.gov ID
- NCT03305419
- Acronym / sponsor ID
- 205184
- Conditions
- Autoimmune Diseases
- Keywords
- Crossover, Sequential, GSK2982772, Safety, Pharmacokinetics, Healthy subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 11 Oct 2017 (actual)
- Primary completion
- 15 Oct 2018 (actual)
- Study completion
- 15 Oct 2018 (actual)
- First posted
- 10 Oct 2017 (actual)
- Results
- Posted 1 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to evaluate the safety, tolerability and PK of GSK2982772, in repeat oral doses in healthy subjects. This study is being conducted to support administration of higher dose levels of GSK2982772 than initially studied in the First Time in Human (FTiH) study. This study will also assess the impact of food during the repeat doses of GSK2982772. This will be a two part study; Part A and Part B. Part A (cohort 1) - single ascending dose, randomized, placebo-controlled, 3-way crossover. Part B (cohorts 2, 3, 4 and 5) - repeat dose, randomized, placebo-controlled, sequential-group. Subjects will be randomized in 3:1 ratio to receive GSK2982772 or placebo in crossover manner on Day 1 of each of the three periods in Part A. Subjects will be randomized in 3:1 ratio to receive GSK2982772 or placebo in sequential groups for 14 days in cohort 2 of Part B and in 9:5 ratio to receive GSK2982772 or placebo in sequential groups for 14 days in cohorts 3, 4 and 5 of Part B. Approximately 66 subjects will be included in this study. The study duration, including screening and follow-up, will not be expected to exceed 13 weeks for Part A and 8 weeks for Part B.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 12
- Model description
- This study will consist of two parts; Part A and Part B. Part A will be a 3-way crossover design and Part B will be a sequential-group design.
| Arm | Type | Receives |
|---|---|---|
| Subjects receiving treatment sequence ABC in cohort 1: Part A | Experimental | Drug: GSK2982772 capsule, Drug: Placebo capsuleEligible subjects will be randomized to receive treatment sequence ABC in Part A; A= GSK2982772 120 mg TID, B= GSK2982772 240 mg TID, and C= GSK2982772 360 mg BID. Subjects will receive oral capsule of GSK2982772 or placebo on Day 1 in each of the 3 treatment periods followed by a wash-out period of at least 7 days between dosing regimens. |
| Subjects receiving treatment sequence ABP in cohort 1: Part A | Experimental | Drug: GSK2982772 capsule, Drug: Placebo capsuleEligible subjects will be randomized to receive treatment sequence ABP in Part A; A= GSK2982772 120 mg TID, B= GSK2982772 240 mg TID, and P= Placebo. Subjects will receive oral capsule of GSK2982772 or placebo on Day 1 in each of the 3 treatment periods followed by a wash-out period of at least 7 days between dosing regimens. |
| Subjects receiving treatment sequence APC in cohort 1: Part A | Experimental | Drug: GSK2982772 capsule, Drug: Placebo capsuleEligible subjects will be randomized to receive treatment sequence APC in Part A; A= GSK2982772 120 mg TID, P= Placebo and C= GSK2982772 360 mg BID. Subjects will receive oral capsule of GSK2982772 or placebo on Day 1 in each of the 3 treatment periods followed by a wash-out period of at least 7 days between dosing regimens. |
| Subjects receiving treatment sequence PBC in cohort 1: Part A | Experimental | Drug: GSK2982772 capsule, Drug: Placebo capsuleEligible subjects will be randomized to receive treatment sequence PBC in Part A; P= Placebo, B= GSK2982772 240 mg TID and C= GSK2982772 360 mg BID. Subjects will receive oral capsule of GSK2982772 or placebo on Day 1 in each of the 3 treatment periods followed by a wash-out period of at least 7 days between dosing regimens. |
| Subjects receiving GSK2982772 120 mg TID in cohort 2 : Part B | Experimental | Drug: GSK2982772 capsuleEligible subjects will receive GSK2982772 oral capsule with a dose of 120 mg TID for 14 days in Part B. |
| Subjects receiving GSK2982772 120 mg TID in cohort 3 : Part B | Experimental | Drug: GSK2982772 capsuleEligible subjects will receive GSK2982772 oral capsule with a dose of 120 mg TID for 14 days in Part B. |
| Subjects receiving GSK2982772 240 mg TID in cohort 4: Part B | Experimental | Drug: GSK2982772 capsuleEligible subjects will receive GSK2982772 oral capsule with a dose of 240 mg TID for 14 days in Part B. |
| Subjects receiving GSK2982772 360 mg BID in cohort 5: Part B | Experimental | Drug: GSK2982772 capsuleEligible subjects will receive GSK2982772 oral capsule with a dose of 360 mg BID for 14 days in Part B. |
| Subjects receiving placebo in cohort 2 : Part B | Placebo comparator | Drug: Placebo capsuleSubjects will receive placebo oral capsule for 14 days in Part B. |
| Subjects receiving placebo in cohort 3 : Part B | Placebo comparator | Drug: Placebo capsuleSubjects will receive placebo oral capsule for 14 days in Part B. |
| Subjects receiving placebo in cohort 4 : Part B | Placebo comparator | Drug: Placebo capsuleSubjects will receive placebo oral capsule for 14 days in Part B. |
| Subjects receiving placebo in cohort 5: Part B | Placebo comparator | Drug: Placebo capsuleSubjects will receive placebo oral capsule for 14 days in Part B. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
- Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, neurological examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator in consultation with the Medical Monitor (if required) agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Body weight >=50 kilograms (kg) and body mass index (BMI) within the range 19 - 30 kg per square meter (kg/m^2) (inclusive).
- A male subject with a female partner of reproductive potential must agree to use contraception during the treatment period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance for a minimum of 28 days prior to the treatment period and for at least 30 days after the last administration of study drug. A WOCBP using a hormonal method of highly effective contraception must also agree to partner use of a male condom during the treatment period and for at least 30 days after the last administration of study drug.
- Capable of giving signed informed consent.
Key exclusion criteria (30 listed)
- History or presence of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
- History of herpes zoster (shingles) reactivation.
- Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest x-rays (posterior anterior and lateral), and TB testing: either a positive tuberculin skin test (TST; defined as a skin induration >5 millimeter (mm) at 48 to 72 hours, regardless of Bacillus Calmette-Guerin (BCG) or other vaccination history) or a positive (not indeterminate) QuantiFERON-TB Gold test.
- ALT >1.5 times upper limit of normal (ULN).
- Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
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 |
|---|---|---|
| GSK2982772 capsuleGSK2982772 will be available as size 00, white, opaque capsule containing white to almost white Solid (120 mg maximum fill per capsule). It will be administered orally with water to receive total dose of 120 mg, 240 mg or 360 mg per randomization. | Drug | Subjects receiving GSK2982772 120 mg TID in cohort 2 : Part B, Subjects receiving GSK2982772 120 mg TID in cohort 3 : Part B, Subjects receiving GSK2982772 240 mg TID in cohort 4: Part B, Subjects receiving GSK2982772 360 mg BID in cohort 5: Part B, Subjects receiving treatment sequence ABC in cohort 1: Part A, Subjects receiving treatment sequence ABP in cohort 1: Part A, Subjects receiving treatment sequence APC in cohort 1: Part A, Subjects receiving treatment sequence PBC in cohort 1: Part A |
| Placebo capsulePlacebo will be available as size 00, white, opaque capsule containing white to almost white Solid. It will be administered orally with water. | Drug | Subjects receiving placebo in cohort 2 : Part B, Subjects receiving placebo in cohort 3 : Part B, Subjects receiving placebo in cohort 4 : Part B, Subjects receiving placebo in cohort 5: Part B, Subjects receiving treatment sequence ABC in cohort 1: Part A, Subjects receiving treatment sequence ABP in cohort 1: Part A, Subjects receiving treatment sequence APC in cohort 1: Part A, Subjects receiving treatment sequence PBC in cohort 1: Part A |
Primary outcome
Number of Subjects With Adverse Events (AEs) and Serious AEs (SAEs): Part A
Time frame: Up to Day 14
An AE is any untoward medical occurrence in a clinical study subjects, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.
Number of Participants With AEs and SAEs: Part B
Time frame: Up to Day 28
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE.
Number of Participants With Worst Case Clinical Chemistry Parameters by Potential Clinical Importance Criteria: Part A
Time frame: Up to Week 9
Blood samples were collected from participants for the analysis of following clinical chemistry parameters: alanine amino transferase (ALT), albumin, alkaline phosphatase, aspartate amino transferase (AST), calcium, creatinine, glucose, potassium, sodium and total bilirubin. PCI ranges were >=2 times Upper Limit of Normal (ULN) units per liter (U/L) for ALT, <30 grams per liter (g/L) for albumin, >=2 times ULN U/L for alkaline phosphatase, >=2 times ULN U/L for AST, <2 or >2.75 millimoles per liter (mmol/L) for calcium, >44.2 micromoles per liter (µmol/L) for creatinine, <3 or >9 mmol/L for glucose, <3 or >5.5 mmol/L for potassium, <130 or >150 mmol/L for sodium and >=1.5 times ULN for total bilirubin. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.
Number of Participants With Worst Case Clinical Chemistry Parameters by Potential Clinical Importance Criteria: Part B
Time frame: Up to Week 4
Blood samples were collected from participants for the analysis of following clinical chemistry parameters: ALT, albumin, alkaline phosphatase, AST, calcium, creatinine, glucose, potassium, sodium and total bilirubin. PCI ranges were >=2 times ULN U/L for ALT, <30 g/L for albumin, >=2 times ULN U/L for alkaline phosphatase, >=2 times ULN U/L for AST, <2 or >2.75 mmol/L for calcium, >44.2 µmol/L for creatinine, <3 or >9 mmol/L for glucose, <3 or >5.5 mmol/L for potassium, <130 or >150 mmol/L for sodium and >=1.5 times ULN for total bilirubin. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.
Number of Participants With Worst Case Hematology Parameters by Potential Clinical Importance Criteria: Part A
Time frame: Up to Week 9
Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, lymphocytes, platelet count, total neutrophils and white blood cell (WBC) counts. PCI ranges were >0.54 or < 0.075 proportion of red blood cells (RBC) in blood for hematocrit, <25 or >180 g/L for hemoglobin, 0.8 x10^9 cells/L for lymphocytes, <1.5 x10^9 cells/L for neutrophils, <100 or >550 x10^9 cells/L for platelets and <3 or 20> x 10^9 cells per liter WBC. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.
Number of Participants With Worst Case Hematology Parameters by Potential Clinical Importance Criteria: Part B
Time frame: Up to Week 4
Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, lymphocytes, platelet count, total neutrophils and WBC counts. PCI ranges were >0.54 or < 0.075 proportion of RBC in blood for hematocrit, <25 or >180 g/L for hemoglobin, 0.8 x10^9 cells/L for lymphocytes, <1.5 x10^9 cells/L for neutrophils, <100 or >550 x10^9 cells/L for platelets and <3 or 20> x 10^9 cells per liter WBC. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.
Number of Participants With Worst Case Urinalysis Results: Part A
Time frame: Up to Week 9
Urine samples were collected from participants for analysis of following parameters: cellular casts, granular casts, hyaline casts, RBC and WBC and were counted as cells per high-power field (cells/HPF). The number of participants with cells in urine has been presented.
Number of Participants With Worst Case Urinalysis Results: Part B
Time frame: Up to Week 4
Urine samples were collected from participants for analysis of following parameters: cellular casts, granular casts, hyaline casts, RBC and WBC and were counted as cells per high-power field (cells/HPF). The number of participants with cells in urine has been presented.
Number of Participants With Abnormal Vital Signs: Part A
Time frame: Up to Week 9
Vital signs were measured in a supine position after 5 minutes rest. The PCI criteria for vital signs included: systolic blood pressure <85 and >160 millimeters of mercury [mmHg]), diastolic blood pressure <45 mmHg and >100 mmHg, heart rate <40 and >100 beats per minute, body temperature <=35.5 and >=37.8 degrees Celsius and respiration rate <=8 and >=20 breaths per minute. Data of participants with potential clinical importance has been reported.
Number of Participants With Abnormal Vital Signs: Part B
Time frame: Up to Week 4
Vital signs were measured in a supine position after 5 minutes rest. The PCI criteria for vital signs included: systolic blood pressure <85 and >160 mmHg, diastolic blood pressure <45 mmHg and >100 mmHg, heart rate <40 and >100 beats per minute, body temperature <=35.5 and >=37.8 degrees Celsius and respiration rate <=8 and >=20 breaths per minute. Data of participants with potential clinical importance has been reported.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings: Part A
Time frame: Up to Day 4
12-lead ECG's were obtained in the supine position after 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Number of Participants With Abnormal ECG Findings: Part B
Time frame: Up to Week 4
12-lead ECG's were obtained in the supine position after 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
40 secondary outcomes
Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours (AUC[0-24]) Following TID Dosing of GSK2982772: Part A
Time frame: Pre-dose, 20, 40minutes, 1 hour, 1hr 30min, 2, 3, 5, 7hour, 7hr 20min,and 7hr 40 min, 8hr, 8hr 30min, 9hr, 10hr, 12hr, 14hr, 14hr 20min, 14hr 40 min, 15hr, 15hr 30min, 16hr, 17hr, 19hr, 22hr, 24hours post dose on Day1
AUC(0-24) Following BID Dosing of GSK2982772: Part A
Time frame: Pre-dose, 20min, 40min, 1hr, 1hr 30min, 2hr, 3hr, 4hr, 6hr, 8hr, 10hr, 12hr, 12hr 20min, 12hr 40min, 13hr, 13hr 30min, 14hr, 15hr, 16hr, 19hr, 22hr, 24hr post dose on Day 1.
AUC[0-24] Following TID Dosing of GSK2982772: Part B
Time frame: Pre-dose, 20, 40minutes, 1 hour, 1hr 30min, 2, 3, 5, 7hour, 7hr 20min,and 7hr 40 min, 8hr, 8hr 30min, 9hr, 10hr, 12hr, 14hr, 14hr 20min, 14hr 40 min, 15hr, 15hr 30min, 16hr, 17hr, 19hr, 22hr, 24hours post dose on Day14
AUC (0-7) Following TID Dosing of GSK2982772 : Part A
Time frame: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Day 1
AUC (7-14) Following TID Dosing of GSK2982772 : Part A
Time frame: 7 hours, 7 hours 20 and 40 minutes, 8 hours, 8 hours 30 minutes, 9, 10, 12, 14 hours on Day 1
AUC (14-24) Following TID Dosing of GSK2982772 : Part A
Time frame: 14 hours, 14 hours 20 and 40 minutes, 15 hours ,15 hours 30 minutes, 16, 19, 22 and 24 hours on Day 1
AUC (0-12) Following BID Dosing of GSK2982772 in Part A
Time frame: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 4, 6, 8, 10 hours,12 hours on Day 1
AUC (12-24) Following BID Dosing of GSK2982772 in Part A
Time frame: 12 hours, 12 hours 20 and 40 minutes, 13 and 13 hours 30 minutes, 14, 15, 16, 19, 22 and 24 hours on Day 1
AUC(0-7) Following TID Dosing of GSK2982772 in Part B
Time frame: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Days 1 and 14
AUC (7-14) Following TID Dosing of GSK2982772 in Part B
Time frame: 7 and 7 hours 20 and 40 minutes, 8 and 8 hours 30 minutes, 9, 10, 12, 14 hours on Day 14
AUC (14-24) Following TID Dosing of GSK2982772 in Part B
Time frame: 14 hours, 14 hours 20 minutes, 14 hours 40 minutes, 15 hours, 15 hours 30 minutes, 16, 17, 19, 22 and 24 hours on Day 14
Maximum Observed Plasma Drug Concentration Cmax (0-7) Following TID Dosing of GSK2982772 in Part A
Time frame: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, and 7 hours post dose on Day 1
Cmax (7-14) Following TID Dosing of GSK2982772 in Part A
Time frame: 7 hours, 7 hours 20 and 40 minutes, 8 and 8 hours 30 minutes, 9, 10, 12, 14 hours post dose on Day 1
Cmax (14-24) Following TID Dosing of GSK2982772 in Part A
Time frame: 14 hours, 14 hours 20 and 40 minutes, 15 and 15 hours 30 minutes, 16, 19, 22 and 24 hours post dose on Day 1
Cmax (0-12) Following BID Dosing of GSK2982772 in Part A
Time frame: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 4, 6, 8, 10 hours and 12 hours post dose on Day 1
Cmax (12-24) Following BID Dosing of GSK2982772 in Part A
Time frame: 12 hours, 12 hours 20 and 40 minutes, 13 and 13 hours 30 minutes, 14, 15, 16, 19, 22 and 24 hours post dose on Day 1
Cmax (0-7) Following TID Dosing of GSK2982772 in Part B
Time frame: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours post dose on Days 1 and 14
Cmax (7-14) Following TID Dosing of GSK2982772 in Part B
Time frame: 7hours, 7 hours 20 and 40 minutes, 8 hours, 8 hours 30 minutes, 9, 10, 12, 14 hours on Day 14
Cmax (14-24) Following TID Dosing of GSK2982772 in Part B
Time frame: 14 hours, 14 hours 20 and 40 minutes, 15 hours, 15 hours 30 minutes, 16, 17, 19, 22 and 24 hours post dose on Day 14
Time to Cmax (Tmax) (0-7) Following TID Dosing of GSK2982772 in Part A
Time frame: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, and 7 hours post dose on Day 1
Tmax (7-14) Following TID Dosing of GSK2982772 in Part A
Time frame: 7hours, 7 hours 20 and 40 minutes, 8 hours, 8 hours 30 minutes, 9, 10, 12, 14 hours post dose on Day 1
Tmax (14-24) Following TID Dosing of GSK2982772 in Part A
Time frame: 14 hours, 14 hours 20 and 40 minutes, 15 hours, 15 hours 30 minutes, 16, 17, 19, 22 and 24 hours post dose on Day 1
Tmax (0-12) Following BID Dosing of GSK2982772 in Part A
Time frame: Pre-dose, 20 and 40 minutes, 1hour, 1 hour 30 minutes, 2, 3, 4, 6, 8, 10 hours and 12 hours post dose on Day 1
Tmax (12-24) Following BID Dosing of GSK2982772 in Part A
Time frame: 12 hours, 12 hours 20 and 40 minutes, 13 hours, 13 hours 30 minutes, 14, 15, 16, 19, 22 and 24 hours post dose on Day 1
Tmax (0-7) Following TID Dosing of GSK2982772 Part B
Time frame: Pre-dose, 20 and 40 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 5, 7 hours post dose on Days 1 and 14
Tmax (7-14) Following TID Dosing of GSK2982772 in Part B
Time frame: 7hours and 7 hours 20 and 40 minutes, 8hours, 8 hours 30 minutes, 9, 10, 12, 14 hours post dose on Day 14
Tmax (14-24) Following TID Dosing of GSK2982772 in Part B
Time frame: 14hours, 14 hours 20 and 40 minutes, 15 hours and 15 hours 30 minutes, 16, 17, 19, 22 and 24 hours post dose on Day 14
Observed Trough Plasma Drug Concentration at 7 Hour (C7),Following TID Dosing of GSK2982772 in Part A
Time frame: 7 hours post-dose on Day 1
Observed Trough Plasma Drug Concentration at 14 Hours (C14) Following TID Dosing of GSK2982772 in Part A
Time frame: 14 hours post-dose on Day 1
C24 Following TID Dosing of GSK2982772 in Part A
Time frame: 24 hours post-dose on Day 1
C12 Following BID Dosing of GSK2982772 in Part A
Time frame: 12 hours post-dose on Day 1
C24 Following BID Dosing of GSK2982772 in Part A
Time frame: 24 hours post-dose on Day 1
C0 Following TID Dosing of GSK2982772 in Part B
Time frame: Pre-dose on Day 14
C7 Following TID Dosing of GSK2982772 in Part B
Time frame: 7 hours post-dose on Days 1 and 14
C14 Following TID Dosing of GSK2982772 in Part B
Time frame: 14 hours post-dose on Day 14
C24 Following TID Dosing of GSK2982772 in Part B
Time frame: 24 hours post-dose on Day 14
AUC([0-7] Following TID Dosing of GSK2982772 in Fed State of Part B
Time frame: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Days 9 and 11
Cmax (0-7) Following TID Dosing of GSK2982772 in Fed State of Part B
Time frame: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Days 9 and 11
Tmax (0-7) Following TID Dosing of GSK2982772 in Fed State of Part B
Time frame: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Days 9 and 11
Ratio of Plasma 4 Beta-hydroxycholesterol to Cholesterol: Part B
Time frame: Pre-dose on Day 1 and 24 hours post first dose on Day 14
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33165774Tompson DJ, Davies C, Scott NE, Cannons EP, Kostapanos M, Gross AS, Powell M, Ino H, Shimamura R, Ogura H, Nagakubo T, Igarashi H, Nakano A. Comparison of the Pharmacokinetics of RIPK1 Inhibitor GSK2982772 in Healthy Western and Japanese Subjects. Eur J Drug Metab Pharmacokinet. 2021 Jan;46(1):71-83. doi: 10.1007/s13318-020-00652-2.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
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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.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK2982772 capsule in people with Autoimmune Diseases, run by GlaxoSmithKline at 1 site in United Kingdom.
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 5 inclusion and 30 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 10 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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 1 Nov 2019). 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?
Number of Subjects With Adverse Events (AEs) and Serious AEs (SAEs): Part A (time frame: Up to Day 14). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03305419, which also lists 1 linked publication.
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 10 Oct 2023; AzTrials last refreshed its copy on 8 Nov 2026.