Healthy VolunteersPhase 1NCT03859323
A Study to Assess the Safety, Tolerability, and Pharmacokinetics of Ascending, Subcutaneous, Single and Multiple Doses of SHP681 (Glucagon-like Peptide-2 [GLP-2] Analog-Fc Fusion) in Healthy Adult Participants
A Phase 1 study testing SHP681 in people with Healthy Volunteers, run by Shire at 1 site in United States.
Trial summary
The purpose of the study is to assess the safety and tolerability of single and multiple ascending subcutaneous (SC) doses of SHP681 in healthy adult participants. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- SHP681
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 104 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Mar 2019to 6 Jan 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Ability to voluntarily provide written, signed, and dated informed consent to participate in the study.
- An understanding, ability, and willingness to fully comply with study procedures and restrictions.
- Age 18-50 inclusive at the time of consent. The date of signature of the informed consent is defined as the beginning of the screening period. This inclusion criterion will only be assessed at the first screening visit.
- Male, or non-pregnant, non-lactating female who agrees to comply with any applicable contraceptive requirements of the protocol or females of non-childbearing potential.
- Considered "healthy" by the investigator. Healthy status is defined by absence of evidence of any active or chronic disease or condition based on a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead electrocardiogram (ECG), hematology, blood chemistry, and urinalysis.
- Body mass index between 18.0 kilograms per square meter (kg/m^2) and 30.0 kg/m^2 inclusive with a body weight 50-100 kg (110-220 pounds [lbs]). This inclusion criterion will only be assessed at the first screening visit.
Who cannot join
- History of any hematological, hepatic, respiratory, cardiovascular, renal, neurological or psychiatric disease, gall bladder removal, or current or recurrent disease that could affect the action, absorption, or disposition of the investigational product, or clinical or laboratory assessments.
- Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or render the participant unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures.
- Known or suspected intolerance or hypersensitivity to the investigational product(s), closely-related compounds, or any of the stated ingredients.
- Significant illness, as judged by the investigator, within 2 weeks of the first dose of investigational product.
- Known history of alcohol or other substance abuse within the last year.
- Donation of blood or blood products (example [eg], plasma or platelets) within 60 days prior to receiving the first dose of investigational product.
Show all 24Show fewer
- Within 30 days prior to the first dose of investigational product:
- Have used an investigational product (if elimination half-life is less than (<) 6 days, otherwise 5 half-lives).
- Have been enrolled in a clinical study.
- Have had any substantial changes in eating habits, as assessed by the investigator.
- Use of dipeptidyl peptidase (DPP)-4 inhibitors within 30 days or 5 half-lives, whichever is greater, prior to administration of the investigational product.
- Confirmed systolic blood pressure greater than (>) 139 millimeters of mercury (mmHg) or <89mmHg, and diastolic blood pressure > 89mmHg or <49 mmHg.
- Twelve-lead ECG demonstrating corrected QT interval by Fredericia (QTcF) >450 millisecond (msec) at screening. If QTcF exceeds 450 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF values should be used to determine the participant's eligibility.
- Positive screen for alcohol or illicit drugs at screening or Day -1.
- Male participants who consume more than 21 units of alcohol per week or 3 units per day. Female participants who consume more than 14 units of alcohol per week or 2 units per day.
- (1 alcohol unit equal to [=] 1 beer or 1 wine (5 ounce [oz] per 150 milliliter [mL]) or 1 liquor (1.5 oz/40 mL) or 0.75 oz alcohol).
- Positive human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody screen.
- Use of tobacco in any form (eg, smoking or chewing) or other nicotine-containing products in any form (eg, gum, patch). Ex-users must report that they have stopped using tobacco for at least 30 days prior to receiving the first dose of investigational product.
- Routine consumption of more than 2 units of caffeine per day or participants who experience headaches associated with caffeine withdrawal. (1 caffeine unit is contained in the following items: one 6 oz (180 mL) cup of coffee, two 12 oz (360 mL) cans of cola, one 12 oz cup of tea, three 1 oz (85 g) chocolate bars. Decaffeinated coffee, tea, or cola are not considered to contain caffeine).
- Prior screen failure (unless Sponsor approval is given), randomization, participation, or enrollment in this study or prior exposure to any GLP-2 analogs.
- Unresected gastrointestinal (GI) polyp, known polyposis condition, or premalignant changes in the GI tract.
- Any history of malignancy in the GI tract or treatment for any other malignancy in the previous 5 years.
- Current use of any medication (including over-the-counter, herbal, or homeopathic preparations; with the exception of hormonal replacement therapy or hormonal contraceptives and occasional use of ibuprofen or acetaminophen and pre-approved medication for sedation or other medications required during or after the endoscopy). Current use is defined as use within 14 days of the first dose of investigational product.
- Findings of subclinical hepatobiliary disease, such as gallstones, on abdominal ultrasound at screening as determined by the Investigator in consultation with the Medical Monitor.
Trial locations and contacts
1 site in 1 country.
United States1 site
New Orleans Center for Clinical Research
Knoxville, Tennessee, 37920
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of Ascending, Subcutaneous, Single and Multiple Doses of SHP681 (GLP-2 Analog-Fc Fusion) in Healthy Adult Subjects
The purpose of the study is to assess the safety and tolerability of single and multiple ascending subcutaneous (SC) doses of SHP681 in healthy adult participants.
Read the detailed description
The study consists of a single ascending dose (SAD) portion and a multiple ascending dose (MAD) portion.
The study duration for the SAD portion of the study consists of a screening period of up to 28 days and 1 treatment period of 29 days. SAD portion of the study contains 5 cohorts and dose escalation will proceed sequentially to assess the following single SC doses of SHP681 or SHP681 matched placebo: 0.2 milligram per kilogram (mg/kg), 0.5 mg/kg, 1 mg/kg, 2 mg/kg, and 4 mg/kg.
The study duration of the MAD portion comprises of a screening period up to 28 days and a treatment period of 57 days for each cohort. MAD portion of the study contains 6 cohorts and dose escalation will proceed sequentially to assess the following SC doses of SHP681 or SHP681 matched placebo: 0.2 mg/kg, 0.5 mg/kg, 1 mg/kg, 2 mg/kg, and 4 mg/kg once weekly for 5 weeks till 5 cohorts and the 6th cohort will receive 4 mg/kg SHP681 or matched placebo every 2 weeks over a 6-week period (3 doses).
- Conditions
- Healthy Volunteers
- Being tested
- SHP681, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SHP681Drug
Participants will receive SC injection of SHP681 in the abdomen.
PlaceboOther
Participants will receive SC injection of placebo matched to SHP681 in the abdomen.
| Study group | Role | What they receive |
|---|---|---|
| Single Ascending Dose (SAD): 0.2 mg/kg | Experimental | Participants will receive single subcutaneous (SC) injection of 0.2 mg/kg SHP681 in the abdomen. Receives: Drug: SHP681 |
| Single Ascending Dose (SAD): 0.5 mg/kg | Experimental | Participants will receive single SC injection of 0.5 mg/kg SHP681 in the abdomen. Receives: Drug: SHP681 |
| Single Ascending Dose (SAD): 1 mg/kg | Experimental | Participants will receive single SC injection of 1 mg/kg SHP681 in the abdomen. Receives: Drug: SHP681 |
| Single Ascending Dose (SAD): 2 mg/kg | Experimental | Participants will receive single SC injection of 2 mg/kg SHP681 in the abdomen. Receives: Drug: SHP681 |
| Single Ascending Dose (SAD): 4 mg/kg | Experimental | Participants will receive single SC injection of 4 mg/kg SHP681 in the abdomen. Receives: Drug: SHP681 |
| Single Ascending Dose (SAD): Placebo | Placebo comparator | Participants will receive single SC injection of placebo matched to SHP681 in the abdomen. Receives: Other: Placebo |
| Multiple Ascending Dose (MAD): 0.2 mg/kg | Experimental | Participants will receive SC injection of 0.2 mg/kg SHP681 once weekly for 5 weeks in the abdomen. Receives: Drug: SHP681 |
| Multiple Ascending Dose (MAD): 0.5 mg/kg | Experimental | Participants will receive SC injection of 0.5 mg/kg SHP681 once weekly for 5 weeks in the abdomen. Receives: Drug: SHP681 |
| Multiple Ascending Dose (MAD): 1 mg/kg | Experimental | Participants will receive SC injection of 1 mg/kg SHP681 once weekly for 5 weeks in the abdomen. Receives: Drug: SHP681 |
| Multiple Ascending Dose (MAD): 2 mg/kg | Experimental | Participants will receive SC injection of 2 mg/kg SHP681 once weekly for 5 weeks in the abdomen. Receives: Drug: SHP681 |
| Multiple Ascending Dose (MAD): 4 mg/kg | Experimental | Participants will receive SC injection of 4 mg/kg SHP681 once weekly for 5 weeks in the abdomen. Receives: Drug: SHP681 |
| Multiple Ascending Dose (MAD): Placebo | Placebo comparator | Participants will receive SC injection of placebo matched to SHP681 once weekly for 5 weeks in the abdomen. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)
Adverse event (AE) was any unfavorable and unintended sign, symptom, or disease temporally associated with study or use of investigational drug product (IP), whether or not the AE was considered related to IP. TEAEs: AEs occurring or worsening at or after first dose of IP or ongoing at time of enrollment. SAE :untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. Severity: Mild: event that does not generally interfere with usual activities of daily living; Moderate: event that interferes with usual activities of daily living, causing discomfort, permanent risk of harm; Severe: AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention.
Measured: From start of study drug administration up to follow-up (Day 29 for SAD)
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)
AE was any unfavorable and unintended sign, symptom, or disease temporally associated with study or use of investigational drug product (IP), whether or not the AE was considered related to IP. TEAEs: AEs occurring or worsening at or after first dose of IP or ongoing at time of enrollment. SAE :untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. Severity: Mild: event that does not generally interfere with usual activities of daily living; Moderate: event that interferes with usual activities of daily living, causing discomfort, permanent risk of harm; Severe: AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention.
Measured: From start of study drug administration up to follow-up (Day 57 for MAD)
Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Single Ascending Dose (SAD) at Day 29
Antibody testing was conducted using an electro chemiluminescent signal method. Number of participants with ADA to SHP681 in SAD at Day 29 were reported.
Measured: Day 29
Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 36
Antibody testing was conducted using an electro chemiluminescent signal method. Number of participants with ADA to SHP681 in MAD at Day 36 were reported.
Measured: Day 36
Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 57
Antibody testing was conducted using an electro chemiluminescent signal method. Number of participants with ADA to SHP681 in MAD at Day 57 were reported.
Measured: Day 57
Secondary outcomes (23)
Maximum Observed Plasma Concentration (Cmax) of SHP681 During Single Ascending Dose (SAD)
Cmax of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Measured: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose
Time of the Last Measurable Concentration (Tlast) of SHP681 During Single Ascending Dose (SAD)
tlast of SHP681 during SAD was reported.
Measured: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose
Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 During Single Ascending Dose (SAD)
tmax of SHP681 during SAD was reported.
Measured: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose
Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 During Single Ascending Dose (SAD)
AUC0-last of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Measured: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose
Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 During Single Ascending Dose (SAD)
AUC0-inf of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Measured: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose
Terminal Half-life (t1/2) of SHP681 During Single Ascending Dose (SAD)
t1/2 of SHP681 during SAD was reported.
Measured: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose
Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Single Ascending Dose (SAD)
Cavg,0-24 of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Measured: Pre-dose, 3, 6, 12, 24 hours post-dose
First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 During Single Ascending Dose (SAD)
Lambda z of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Measured: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose
Apparent Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUC0-inf (CL/F) of SHP681 During Single Ascending Dose (SAD)
CL/F of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Measured: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose
Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 During Single Ascending Dose (SAD)
Vz/F of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Measured: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose
Average Concentration From Time Zero to 24 Hours Post First Dose (Cavg,0-24) of SHP681 Post First Dose During Multiple Ascending Dose (MAD)
Cavg,0-24 of SHP681 post first dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Measured: 3, 6, 12, 24 hours post-dose on Day 1
Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)
Ctrough of SHP681 for the First 5 cohorts and immediately before 2nd and 3rd dose of the 6th MAD cohort during MAD was reported.
Measured: Pre-dose on Days 8, 15, 22 and 29
Maximum Concentration During the Dosing Interval Occurring at Tmax (Cmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)
Cmax of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Measured: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
Time of the Last Measurable Concentration (Tlast) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)
Tlast of SHP681 post fifth dose during MAD was reported.
Measured: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)
tmax of SHP681 post fifth dose during MAD was reported.
Measured: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
Area Under the Curve for the Defined Interval Between Doses (Only Calculated if Interpretable) (AUC0-tau) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)
AUC0-tau of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Measured: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)
AUC0-last of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Measured: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)
AUC0-inf of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Measured: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Multiple Ascending Dose (MAD)
Cavg,0-24 of SHP681 during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Measured: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
Terminal Half-life (t1/2) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)
t1/2 of SHP681 post fifth dose during MAD was reported.
Measured: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)
Lambda z of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Measured: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
Apparent Total Body Clearance Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUCtau (CL/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)
CL/F of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Measured: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)
Vz/F of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Measured: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2019
- Study start26 Mar 2019
- Primary completion6 Jan 2020
- Study completion6 Jan 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 VolunteersStudies of the same condition, open and under way.
- 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
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Shire
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03859323
- Sponsor's protocol ID
- SHP681-101
- Status last verified
- Feb 2021
- First submitted
- 28 Feb 2019
- Last updated
- 25 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled, Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of Ascending, Subcutaneous, Single and Multiple Doses of SHP681 (GLP-2 Analog-Fc Fusion) in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT03859323
- Acronym / sponsor ID
- SHP681-101
- Conditions
- Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 26 Mar 2019 (actual)
- Primary completion
- 6 Jan 2020 (actual)
- Study completion
- 6 Jan 2020 (actual)
- First posted
- 1 Mar 2019 (actual)
- Results
- Posted 25 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to assess the safety and tolerability of single and multiple ascending subcutaneous (SC) doses of SHP681 in healthy adult participants.
Detailed description
The study consists of a single ascending dose (SAD) portion and a multiple ascending dose (MAD) portion.
The study duration for the SAD portion of the study consists of a screening period of up to 28 days and 1 treatment period of 29 days. SAD portion of the study contains 5 cohorts and dose escalation will proceed sequentially to assess the following single SC doses of SHP681 or SHP681 matched placebo: 0.2 milligram per kilogram (mg/kg), 0.5 mg/kg, 1 mg/kg, 2 mg/kg, and 4 mg/kg.
The study duration of the MAD portion comprises of a screening period up to 28 days and a treatment period of 57 days for each cohort. MAD portion of the study contains 6 cohorts and dose escalation will proceed sequentially to assess the following SC doses of SHP681 or SHP681 matched placebo: 0.2 mg/kg, 0.5 mg/kg, 1 mg/kg, 2 mg/kg, and 4 mg/kg once weekly for 5 weeks till 5 cohorts and the 6th cohort will receive 4 mg/kg SHP681 or matched placebo every 2 weeks over a 6-week period (3 doses).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Single Ascending Dose (SAD): 0.2 mg/kg | Experimental | Drug: SHP681Participants will receive single subcutaneous (SC) injection of 0.2 mg/kg SHP681 in the abdomen. |
| Single Ascending Dose (SAD): 0.5 mg/kg | Experimental | Drug: SHP681Participants will receive single SC injection of 0.5 mg/kg SHP681 in the abdomen. |
| Single Ascending Dose (SAD): 1 mg/kg | Experimental | Drug: SHP681Participants will receive single SC injection of 1 mg/kg SHP681 in the abdomen. |
| Single Ascending Dose (SAD): 2 mg/kg | Experimental | Drug: SHP681Participants will receive single SC injection of 2 mg/kg SHP681 in the abdomen. |
| Single Ascending Dose (SAD): 4 mg/kg | Experimental | Drug: SHP681Participants will receive single SC injection of 4 mg/kg SHP681 in the abdomen. |
| Single Ascending Dose (SAD): Placebo | Placebo comparator | Other: PlaceboParticipants will receive single SC injection of placebo matched to SHP681 in the abdomen. |
| Multiple Ascending Dose (MAD): 0.2 mg/kg | Experimental | Drug: SHP681Participants will receive SC injection of 0.2 mg/kg SHP681 once weekly for 5 weeks in the abdomen. |
| Multiple Ascending Dose (MAD): 0.5 mg/kg | Experimental | Drug: SHP681Participants will receive SC injection of 0.5 mg/kg SHP681 once weekly for 5 weeks in the abdomen. |
| Multiple Ascending Dose (MAD): 1 mg/kg | Experimental | Drug: SHP681Participants will receive SC injection of 1 mg/kg SHP681 once weekly for 5 weeks in the abdomen. |
| Multiple Ascending Dose (MAD): 2 mg/kg | Experimental | Drug: SHP681Participants will receive SC injection of 2 mg/kg SHP681 once weekly for 5 weeks in the abdomen. |
| Multiple Ascending Dose (MAD): 4 mg/kg | Experimental | Drug: SHP681Participants will receive SC injection of 4 mg/kg SHP681 once weekly for 5 weeks in the abdomen. |
| Multiple Ascending Dose (MAD): Placebo | Placebo comparator | Other: PlaceboParticipants will receive SC injection of placebo matched to SHP681 once weekly for 5 weeks in the abdomen. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Ability to voluntarily provide written, signed, and dated informed consent to participate in the study.
- An understanding, ability, and willingness to fully comply with study procedures and restrictions.
- Age 18-50 inclusive at the time of consent. The date of signature of the informed consent is defined as the beginning of the screening period. This inclusion criterion will only be assessed at the first screening visit.
- Male, or non-pregnant, non-lactating female who agrees to comply with any applicable contraceptive requirements of the protocol or females of non-childbearing potential.
- Considered "healthy" by the investigator. Healthy status is defined by absence of evidence of any active or chronic disease or condition based on a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead electrocardiogram (ECG), hematology, blood chemistry, and urinalysis.
Key exclusion criteria (24 listed)
- History of any hematological, hepatic, respiratory, cardiovascular, renal, neurological or psychiatric disease, gall bladder removal, or current or recurrent disease that could affect the action, absorption, or disposition of the investigational product, or clinical or laboratory assessments.
- Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or render the participant unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures.
- Known or suspected intolerance or hypersensitivity to the investigational product(s), closely-related compounds, or any of the stated ingredients.
- Significant illness, as judged by the investigator, within 2 weeks of the first dose of investigational product.
- Known history of alcohol or other substance abuse within the last year.
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 |
|---|---|---|
| SHP681Participants will receive SC injection of SHP681 in the abdomen. | Drug | Multiple Ascending Dose (MAD): 0.2 mg/kg, Multiple Ascending Dose (MAD): 0.5 mg/kg, Multiple Ascending Dose (MAD): 1 mg/kg, Multiple Ascending Dose (MAD): 2 mg/kg, Multiple Ascending Dose (MAD): 4 mg/kg, Single Ascending Dose (SAD): 0.2 mg/kg, Single Ascending Dose (SAD): 0.5 mg/kg, Single Ascending Dose (SAD): 1 mg/kg, Single Ascending Dose (SAD): 2 mg/kg, Single Ascending Dose (SAD): 4 mg/kg |
| PlaceboParticipants will receive SC injection of placebo matched to SHP681 in the abdomen. | Other | Multiple Ascending Dose (MAD): Placebo, Single Ascending Dose (SAD): Placebo |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)
Time frame: From start of study drug administration up to follow-up (Day 29 for SAD)
Adverse event (AE) was any unfavorable and unintended sign, symptom, or disease temporally associated with study or use of investigational drug product (IP), whether or not the AE was considered related to IP. TEAEs: AEs occurring or worsening at or after first dose of IP or ongoing at time of enrollment. SAE :untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. Severity: Mild: event that does not generally interfere with usual activities of daily living; Moderate: event that interferes with usual activities of daily living, causing discomfort, permanent risk of harm; Severe: AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention.
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)
Time frame: From start of study drug administration up to follow-up (Day 57 for MAD)
AE was any unfavorable and unintended sign, symptom, or disease temporally associated with study or use of investigational drug product (IP), whether or not the AE was considered related to IP. TEAEs: AEs occurring or worsening at or after first dose of IP or ongoing at time of enrollment. SAE :untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. Severity: Mild: event that does not generally interfere with usual activities of daily living; Moderate: event that interferes with usual activities of daily living, causing discomfort, permanent risk of harm; Severe: AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention.
Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Single Ascending Dose (SAD) at Day 29
Time frame: Day 29
Antibody testing was conducted using an electro chemiluminescent signal method. Number of participants with ADA to SHP681 in SAD at Day 29 were reported.
Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 36
Time frame: Day 36
Antibody testing was conducted using an electro chemiluminescent signal method. Number of participants with ADA to SHP681 in MAD at Day 36 were reported.
Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 57
Time frame: Day 57
Antibody testing was conducted using an electro chemiluminescent signal method. Number of participants with ADA to SHP681 in MAD at Day 57 were reported.
23 secondary outcomes
Maximum Observed Plasma Concentration (Cmax) of SHP681 During Single Ascending Dose (SAD)
Time frame: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose
Time of the Last Measurable Concentration (Tlast) of SHP681 During Single Ascending Dose (SAD)
Time frame: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose
Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 During Single Ascending Dose (SAD)
Time frame: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose
Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 During Single Ascending Dose (SAD)
Time frame: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose
Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 During Single Ascending Dose (SAD)
Time frame: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose
Terminal Half-life (t1/2) of SHP681 During Single Ascending Dose (SAD)
Time frame: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose
Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Single Ascending Dose (SAD)
Time frame: Pre-dose, 3, 6, 12, 24 hours post-dose
First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 During Single Ascending Dose (SAD)
Time frame: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose
Apparent Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUC0-inf (CL/F) of SHP681 During Single Ascending Dose (SAD)
Time frame: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose
Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 During Single Ascending Dose (SAD)
Time frame: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose
Average Concentration From Time Zero to 24 Hours Post First Dose (Cavg,0-24) of SHP681 Post First Dose During Multiple Ascending Dose (MAD)
Time frame: 3, 6, 12, 24 hours post-dose on Day 1
Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)
Time frame: Pre-dose on Days 8, 15, 22 and 29
Maximum Concentration During the Dosing Interval Occurring at Tmax (Cmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)
Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
Time of the Last Measurable Concentration (Tlast) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)
Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)
Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
Area Under the Curve for the Defined Interval Between Doses (Only Calculated if Interpretable) (AUC0-tau) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)
Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)
Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)
Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Multiple Ascending Dose (MAD)
Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
Terminal Half-life (t1/2) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)
Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)
Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
Apparent Total Body Clearance Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUCtau (CL/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)
Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)
Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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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.
Study Director study director
Shire
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 SHP681 in people with Healthy Volunteers, run by Shire at 1 site in United States.
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 6 inclusion and 24 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 25 Feb 2021. 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 States. 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 25 Feb 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?
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD) (time frame: From start of study drug administration up to follow-up (Day 29 for SAD)). The study lists 5 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 25 Feb 2021.