Phase 2
Completed N=113
A Multiple-ascending-dose Study to Evaluate the Efficacy, Safety, and Pharmacokinetics (PK) of MEDI0382 in Overweight and Obese Participants With Type 2 Diabetes Mellitus
Source: ClinicalTrials.gov NCT02548585 ↗Enrolled (actual)
113
Serious AEs
1.8%
Results posted
Apr 2019
Primary outcomePrimary: Percent Change From Baseline in Mixed-meal Test (MMT) Glucose Area Under the Concentration-time Curve From Time 0 to 4 Hours to the End of Treatment (EOT) (Cohort 4) — -9.24; -33.81 Percent change — p=< 0.0001
Summary
A Phase 1/2, multiple dose study with 6 cohorts of ascending doses designed to evaluate the efficacy, safety and pharmacokinetics (PK) of MEDI0382 in participants with Type 2 Diabetes Mellitus (T2DM).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline in Mixed-meal Test (MMT) Glucose Area Under the Concentration-time Curve From Time 0 to 4 Hours to the End of Treatment (EOT) (Cohort 4) |
-9.24; -33.81 | < 0.0001 sig |
| PRIMARY Change From Baseline in Body Weight to the EOT (Cohort 4) |
-1.71; -3.83 | 0.0008 sig |
| SECONDARY Percent Change From Baseline in MMT Glucose AUC0-4h to the EOT (Cohorts 1, 2, 3, 5, and 6) |
-14.60; -41.80; -15.07; -36.73; -0.47; -39.58 | — |
| SECONDARY Change From Baseline in Body Weight to the EOT (Cohorts 1, 2, 3, 5, and 6) |
-1.20; -2.32; -1.00; -1.52; -2.90; -4.63 | — |
| SECONDARY Percent Change From Baseline in Hemoglobin A1c (HbA1c) to the EOT (Cohorts 4, 5, and 6) |
-0.58; -0.92; -0.10; -0.55; -0.18; -0.42 | — |
| SECONDARY Change From Baseline in Fructosamine to the EOT (Cohorts 4, 5, and 6) |
-33.7; -67.9; -27.8; -47.4; -48.8; -47.5 | — |
| SECONDARY Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6) |
-32.44; -74.48; -49.86; -54.06; -4.20; -63.67 | — |
| SECONDARY Percent Change From Baseline in Glucose Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24h) After MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6) |
-21.80; -28.34; 0.80; -29.32; -13.80; -27.07 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) |
2; 6; 3; 5; 3; 7 | — |
| SECONDARY Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs |
0; 1; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs |
0; 0; 0; 1; 0; 0 | — |
| SECONDARY Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) |
1; 4; 0; 2; 0; 2 | — |
| SECONDARY Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) |
2; 2; 0; 1; 0; 1 | — |
| SECONDARY Terminal Elimination Half Life (t1/2) of MEDI0382 (Cohorts 1, 2, and 3) |
8.5; 10.3; 11.7; 8.3; 11.3; 11.3 | — |
| SECONDARY Accumulation Ratio (Rac) of MEDI0382 (Cohorts 1, 2, and 3) |
NA; NA; 1.3; NA; 1.1; 1.3 | — |
| SECONDARY Area Under the Concentration Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) |
82.21; 174.58; 107.01; 194.78; 164.05; 157.31 | — |
| SECONDARY Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) |
103.46; 207.15; 184.68; 242.60; 238.22; 215.80 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) |
4.97; 9.66; 6.26; 10.57; 11.64; 9.57 | — |
| SECONDARY Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) |
0.705; 2.685; 2.372; 3.521; 2.635; 3.59 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) |
8; 6; 6; 6; 4; 6 | — |
| SECONDARY Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) |
0; 0; 1; 0; 0; 0 | — |
| SECONDARY Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6) |
10.83; -9.37; -3.67; 36.32; -20.43; -17.47 | — |
| SECONDARY Percent Change From Baseline in Proinsulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) |
-3.27; -52.10; -33.13; -36.77; 81.27; -54.13 | — |
| SECONDARY Percent Change From Baseline in C-peptide AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) |
10.17; -3.82; -1.43; 39.78; 79.37; -9.07 | — |
| SECONDARY Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) |
8.30; -33.67; -10.40; -50.45; -2.87; -40.36 | — |
Eligibility Criteria
Inclusion Criteria
- Diagnosis of T2DM
- Must provide written informed consent
- Body mass index greater than (>) 27 and less than ( =) 200 mg/dL
- Positive Hepatitis B, Hepatitis C or human immunodeficiency virus test or use of antiretroviral medications at screening.
- Concurrent or previous use of a glucagon-like peptide 1 receptor agonist
- Current or previous use of systemic corticosteroids within the past 28 days prior to screening
- Use of any medicinal products or herbal preparations licensed for control of body weight or appetite is prohibited.
- Known or suspected history of alcohol or drug abuse within the past 3 years.
- Positive drug screen
Data sourced from ClinicalTrials.gov (NCT02548585). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.