A Phase 2a Randomized, Blinded, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of MEDI0382 in Overweight/Obese Subjects With Type 2 Diabetes Mellitus
Overview
- Phase
- Phase 2
- Intervention
- MEDI0382
- Conditions
- Type 2 Diabetes Mellitus
- Sponsor
- MedImmune LLC
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Through the End of the Up-titration Period
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
This is a Phase 2a, randomized, blinded, placebo-controlled study in up to 20 overweight or obese participants with type 2 diabetes mellitus. The participants will participate in the study for approximately 18 weeks, including screening, run-in and treatment periods and a safety follow-up.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants aged 18 to 74 years (inclusive) at screening.
- •Provision of signed and dated written informed consent (with the exception of consent for genetic and non-genetic research) prior to any study specific procedures.
- •Body mass index (BMI) between 27 and 35 kg/m\^2 (inclusive) at screening.
- •Hemoglobin A1c (HbA1c) range of 6.5% to 8.5% (inclusive) at screening (Note: Participants may be re-tested for the HbA1c entry criterion only once.).
- •Willing and able to self-inject study drug for the duration of the study.
- •Diagnosed with type 2 diabetes mellitus with glucose control managed with metformin monotherapy where no significant dose change (increase or decrease \>= 500 mg/day) has occurred in the three months prior to screening.
- •Female participants must have a negative pregnancy test at screening and randomization, and must not be lactating.
- •Female participants of childbearing potential who are sexually active with a male partner must be using at least one highly effective method of contraception from screening and up to 4 weeks after the last dose of study drug.
Exclusion Criteria
- •History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the study drug, put the participant at risk, influence the participant's ability to participate or affect the interpretation of the results of the study and/or any participant unable or unwilling to follow study procedures during the run-in period.
- •Any participant who has received another study drug as part of a clinical study or a glucagon-like peptide-1 (GLP-1) analogue containing preparation within the last 30 days or 5 half-lives of the drug (whichever is longer) at the time of screening.
- •Concurrent participation in another study of any kind and repeat randomization in this study is prohibited.
- •Any participant who has received any of the following medications prior to the start of the study:
- •Herbal preparations or drugs licensed for control of body weight or appetite
- •Opiates, domperidone, metoclopramide, or other drugs known to alter gastric emptying
- •Antimicrobials within the quinolone, macrolide or azole class
- •Any change in antihypertensive medication
- •Aspirin (acetylsalicylic acid)
- •Paracetamol (acetaminophen) or paracetamol-containing preparations
Arms & Interventions
MEDI0382 Cohort 1
Participants will receive subcutaneous (SC) dose of MEDI0382 uptitrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week treatment extension period (TEP).
Intervention: MEDI0382
Placebo Cohort 1
Participants will receive SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the uptitration period and thereafter once daily through 3 week TEP.
Intervention: Placebo
MEDI0382 Cohort 2
Participants will receive SC dose of MEDI0382 uptitrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Intervention: MEDI0382
Placebo Cohort 2
Participants will receive SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Through the End of the Up-titration Period
Time Frame: Baseline (Day -1) through Day 56 (end of Up-titration period)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Number of Participants With TEAEs and TESAEs Through the End of the Follow-up Period
Time Frame: Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs Through the End of the Up-titration Period
Time Frame: Baseline (Day -1) through Day 56 (end of Up-titration period)
Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs is defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, QT intervals, and QTcF intervals from the primary lead of the digital 12-lead ECG.
Number of Participants With Abnormal ECGs Reported as TEAEs Through the End of the Follow-up Period
Time Frame: Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)
Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs is defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, QT intervals, and QTcF intervals from the primary lead of the digital 12-lead ECG.
Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Up-titration Period
Time Frame: Baseline (Day -1) through Day 56 (end of Up-titration period)
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate).
Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Follow-up Period
Time Frame: Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)
Number of participants with abnormal physical examinations reported as TEAEs are reported. Abnormal physical examination findings are defined as any abnormal finding in the following body systems: immunologic/allergy; head, ears, eyes, nose, and throat; respiratory; cardiovascular; gastrointestinal; musculoskeletal; neurological psychiatric; dermatologic; hematologic/lymphatic; and endocrine.
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Up-titration Period
Time Frame: Baseline (Day -1) through Day 56 (end of Up-titration period)
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, and urine.
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Follow-up Period
Time Frame: Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, and urine.
Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Follow-up Period
Time Frame: Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate).
Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Up-titration Period
Time Frame: Baseline (Day -1) through Day 56 (end of Up-titration period)
Number of participants with abnormal physical examinations reported as TEAEs are reported. Abnormal physical examinations findings are defined as any abnormal finding in the following body systems: immunologic/allergy; head, ears, eyes, nose, and throat; respiratory; cardiovascular; gastrointestinal; musculoskeletal; neurological psychiatric; dermatologic; hematologic/lymphatic; and, endocrine.
Secondary Outcomes
- Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM(Baseline (Day -1), Days 7, 14, 21, 28, 35, 42, 49, 56 of the up-titration period, and Day77 (end of the treatment extension period))
- Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM(Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period)
- Change From Baseline in HbA1c(Baseline (Day -1) through Day 77 (end of the treatment extension period))
- Percentage of Participants Achieving Greater Than 5% Body Weight Loss From Baseline to the End of the Treatment Extension Period(Baseline (Day -1) through Day 77 (end of the treatment extension period))
- Area Under the Plasma Concentration Time Curve Over a Dosing Interval (AUCτ) of MEDI0382(Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84)
- Maximum Observed Serum Concentration (Cmax) of MEDI0382(Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84)
- Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382(Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84)
- Trough Plasma Concentration (Ctrough) of MEDI0382(Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84)
- Observed Accumulation Ratio (Ro) of MEDI0382 Calculated Using AUC(Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84)
- Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0382 Treatment(Pre-dose (Day -2), Days 7, 14, 35, 42, 56; Day 21 of 3 week treatment extension, and 28 days post last dose (approximately 5 months))
- Change From Baseline in Daily (24 Hours) Average Glucose Levels Over Time as Measured by Continuous Glucose Monitoring (CGM)(Baseline (Day -1) through Day 56 (end of the up-titration period), Day 77 (end of the treatment extension period) and Day 91 (end of the follow-up period))
- Change From Baseline in 7-day Average Glucose Levels Over Time as Measured by CGM(Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period)
- Absolute Change From Baseline in Body Weight(Baseline (Day -1) through Day 56 (end of the up-titration period) and Day 77 (end of the TEP))
- Percentage Change From Baseline in Glucose Area Under Concentration Time-curve Over 4 Hours (AUC4Hrs) During a Standardized Breakfast, Lunch, and Evening Meal Over Time as Measured by CGM(Baseline (Day -1) through Day 7 (end of Week 1), Day 56 (end of the up-titration period), and Day 77 (end of the treatment extension period))
- Change From Baseline in Coefficient of Variation (CV) in Glucose Over 7 Days as Measured by CGM(Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period)
- Change From Baseline in Estimated Hemoglobin A1c (HbA1c) Based on 7-day CGM Glucose Over Time(Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period)
- Change From Baseline in Fasting Plasma Glucose Over Time(Baseline (Day -1), Days 7, 14, 21, 28, 35, 42, 49, 56 of the up-titration period, and Day77 (end of the treatment extension period))
- Percentage Change From Baseline in Body Weight(Baseline (Day -1) through Day 56 (end of the up-titration period) and Day 77 (end of the TEP))
- Absolute Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period(Baseline (Day -1), Days 7, 14, 35, 42, 49, and 56)
- Percentage Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period(Baseline (Day -1), Days 7, 14, 35, 42, 49, and 56)