Phase 1
Completed N=87
Study of the Safety and Efficacy of MK-8521 Compared to Placebo and a Diabetes Drug in Participants With Type 2 Diabetes Mellitus (MK-8521-003)
Source: ClinicalTrials.gov NCT01982630 ↗Enrolled (actual)
87
Serious AEs
0.9%
Results posted
Mar 2022
Primary outcomePrimary: Number of Participants Experiencing Adverse Events (AEs) in Part 1 — 5; 5; 1; 4 Participants
Summary
This study will evaluate the safety, efficacy, and pharmacokinetics of MK-8521 given once daily compared to placebo and another diabetes drug in participants with Type 2 diabetes mellitus (T2DM).
This study was modified by a protocol amendment to a 2-part trial to further test the safety and tolerability of MK-8521 at higher doses and to compare MK-8521 pharmacokinetics between participants with T2DM and healthy participants. An additional cohort of T2DM participants and a cohort of non-diabetic obese participants has been added.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Experiencing Adverse Events (AEs) in Part 1 |
5; 5; 1; 4; 2; 7 | — |
| PRIMARY Number of Participants Experiencing Adverse Events (AEs) in Part 2 |
8; 14; 6; 13; 8; 8 | — |
| PRIMARY Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs) in Part 1 |
2; 0; 0; 0; 1; 0 | — |
| PRIMARY Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs) in Part 2 |
0; 0; 0; 1; 0; 0 | — |
| PRIMARY Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 7 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 |
7.19; 1.17; 7.42; 5.69 | — |
| PRIMARY Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 7 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
1.99; 4.10; -0.54 | — |
| PRIMARY Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 14 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 |
9.67; 3.90; 10.32; 9.81 | — |
| PRIMARY Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 14 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
5.05; 5.93; -0.20 | — |
| PRIMARY Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 19 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
5.62; 6.20; -2.14 | — |
| PRIMARY Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 24 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
7.30; 5.95; -0.99 | — |
| PRIMARY Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 29 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
8.30; 5.84; -1.31 | — |
| PRIMARY Change From Baseline in Peak Heart Rate (PHR) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
7.94; 11.91; 8.65 | — |
| PRIMARY Change From Baseline in Peak Heart Rate (PHR) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
11.41; 13.00; 8.90 | — |
| PRIMARY Change From Baseline in Peak Heart Rate (PHR) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
11.26; 14.75; 7.30 | — |
| PRIMARY Change From Baseline in Peak Heart Rate (PHR) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
14.09; 14.06; 9.39 | — |
| PRIMARY Change From Baseline in Peak Heart Rate (PHR) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
16.01; 12.66; 7.13 | — |
| PRIMARY Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 7 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
1.65; 5.20; 0.59 | — |
| PRIMARY Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 14 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
4.22; 5.38; -4.42 | — |
| PRIMARY Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 19 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
6.41; 10.44; -3.82 | — |
| PRIMARY Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 24 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
7.51; 9.63; -5.82 | — |
| PRIMARY Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 29 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
9.41; 7.30; -1.02 | — |
| PRIMARY Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 |
6.11; 2.25; 14.4; 5.63; 32.8; 12.6 | — |
| PRIMARY Maximum Concentration (Cmax) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 |
0.350; 0.128; 0.710; 0.275 | — |
| PRIMARY Maximum Concentration (Cmax) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 |
1.70; 0.619 | — |
| PRIMARY Trough Concentration (Ctrough) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 |
0.322; 0.119; 0.442; 0.207; 1.16; 0.506 | — |
| PRIMARY Time to Maximum Concentration (Tmax) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 |
16; 16; 7; 6 | — |
| PRIMARY Time to Maximum Concentration (Tmax) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 |
8; 6 | — |
| PRIMARY Apparent Terminal Half Life (t1/2) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 |
— | — |
| PRIMARY Apparent Terminal Half Life (t1/2) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 |
15.6; 17.2 | — |
| PRIMARY Accumulation Ratio of the Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 |
2.31; 2.50 | — |
| PRIMARY Accumulation Ratio of the Maximum Concentration (Cmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 |
2.00; 2.14 | — |
| PRIMARY Accumulation Ratio of the Trough Concentration (Ctrough) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 |
1.37; 1.73 | — |
| PRIMARY Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2 |
6.46; 7.68; 15.1; 15.0; 30.0; 34.4 | — |
| PRIMARY Accumulation Ratio of the Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2 |
2.33; 1.95 | — |
| SECONDARY Change From Baseline in Fasting Plasma Glucose (FPG) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 |
-23.57; -39.00; -59.11; -11.13 | — |
| SECONDARY Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 |
-41.29; -48.50; -59.25; -13.50 | — |
| SECONDARY Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 |
-24.08; -27.54; -53.64; 2.36 | — |
| SECONDARY Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 |
-37.24; -45.63; -52.20; -2.00 | — |
| SECONDARY Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
-45.89; -39.80; -14.69 | — |
| SECONDARY Change From Baseline in Fasting Plasma Glucose (FPG) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
-44.22; -47.33; -16.74 | — |
| SECONDARY Change From Baseline in Fasting Plasma Glucose (FPG) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
-40.14; -50.14; -44.73 | — |
| SECONDARY Change From Baseline in Fasting Plasma Glucose (FPG) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
-52.54; -52.06; -37.55 | — |
| SECONDARY Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
-47.52; -51.24; -3.84 | — |
| SECONDARY Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
-52.23; -57.43; -18.22 | — |
| SECONDARY Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
-50.44; -60.66; -26.71 | — |
| SECONDARY Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
-53.44; -59.72; -29.96 | — |
| SECONDARY Maximum Concentration (Cmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2 |
0.35; 0.411; 0.719; 0.742; 1.43; 1.72 | — |
| SECONDARY Trough Concentration (Ctrough) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2 |
0.331; 0.388; 0.533; 0.492; 1.07; 1.12 | — |
| SECONDARY Time to Maximum Concentration (Tmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2 |
16; 16; 10; 10; 6; 6 | — |
| SECONDARY Apparent Terminal Half Life (t1/2) of MK-8521 on Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 |
15.4 | — |
| SECONDARY Apparent Terminal Half Life (t1/2) of MK-8521 on Day 14 for Non-Diabetic Overweight/Obese Participants in Part 2 |
14.4 | — |
Eligibility Criteria
Inclusion Criteria
- Male, or female of non-childbearing potential with Type 2 diabetes mellitus (Parts 1 and 2) or non-diabetic (Part 2)
- Body mass index (BMI) between: ≥27 and ≤40 kg/m^2
- A1C (average blood sugar for the past 2 to 3 months) value ≥7.0 and ≤11.0 % (Part 1) or ≥ 6.5 and ≤11.0 % (Part 2) at the time of screening (T2DM participants)
- A1C value 160 mm Hg and/or diastolic blood pressure >90 mm Hg (after at least a 10-minute seated rest) and blood pressure is considered unlikely to be below these limits by Day-1 (Randomization) with initiation or adjustment of antihypertensive medication
- Event of severe hypoglycemia with seizure or loss of consciousness in the past 12 months
- Treated with anti-hyperglycemic agents other than metformin within the last 12 weeks
- Previous exposure to any glucagon-like peptide-1 (GLP-1) receptor agonist (e.g. Byetta™, Victoza™ or investigational agents)
Data sourced from ClinicalTrials.gov (NCT01982630). 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.