Phase 1
Completed N=61
A Single and Multiple-Dose Study of MK-8521 in Healthy and Obese Males (MK-8521-002)
Source: ClinicalTrials.gov NCT02055547 ↗Enrolled (actual)
61
Serious AEs
0.0%
Results posted
Jul 2020
Primary outcomePrimary: Number of Participants Who Experienced at Least One Adverse Event (AE) (Part 1) — 3; 4; 2; 0 Participants
Summary
This study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of MK-8521.
Part 1 primary hypothesis: Administration of single subcutaneous (SC) doses of MK-8521 is sufficiently safe and well- tolerated in healthy participants, based on assessment of clinical and laboratory adverse experiences, to permit continued clinical investigation.
Part 2: Administration of multiple once daily SC doses of MK-8521 is sufficiently safe and well-tolerated in healthy lean and obese participants, based on assessment of clinical and laboratory adverse experiences, to permit continued clinical investigation.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Who Experienced at Least One Adverse Event (AE) (Part 1) |
3; 4; 2; 0; 5; 10 | — |
| PRIMARY Number of Participants Who Discontinued Treatment Due to an AE (Part 1) |
0; 0; 0; 0; 0; 1 | — |
| PRIMARY Area Under the Concentration Time Curve of MK-8521 From 0 to Infinity (AUC0-∞) After a Single Dose (Part 1) |
48.7; 163; 84.4; 101; 109 | — |
| PRIMARY Peak Plasma Concentration (Cmax) of Participants Treated With a Single Dose of MK-8521 (Part 1) |
1.24; 4.29; 2.63; 3.10; 3.54 | — |
| PRIMARY Time Taken to Reach Cmax (Tmax) for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 1) |
14; 10; 11; 12; 14 | — |
| PRIMARY Apparent Terminal Half-life (t1/2) for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 1) |
13.8; 13.7; 14.8; 14.1; 13.8 | — |
| PRIMARY Number of Participants With an Adverse Event (AE) (Part 2) |
5; 5; 5; 4; 3 | — |
| PRIMARY Number of Participants Who Discontinued Treatment Due to an AE (Part 2) |
0; 1; 0; 0; 0 | — |
| PRIMARY AUC 0-24hr for Plasma Concentration of Participants Treated After Multiple Doses of MK-8521 (Part 2, Panels C, D, and E) |
12.0; 23.1; 33.5; 22.8; 43.3; 60.7 | — |
| PRIMARY AUC 0-24hr for Plasma Concentration of Participants Treated After Multiple Doses of MK-8521 (Part 2, Panel F) |
8.85; 24.8; 54.6 | — |
| PRIMARY Cmax for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panels C, D, and E) |
0.642; 1.25; 1.85; 1.11; 2.21; 3.12 | — |
| PRIMARY Cmax for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F) |
0.511; 1.15; 2.56 | — |
| PRIMARY Trough Plasma Concentration (Ctrough) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panels C, D, and E) |
0.493; 1.00; 1.33; 0.721; 1.33; 2.01 | — |
| PRIMARY Trough Plasma Concentration (Ctrough) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F) |
0.498; 0.935; 2.09 | — |
| PRIMARY Tmax for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panels C, D, and E) |
12; 10; 10; 9; 8; 9 | — |
| PRIMARY Tmax for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F) |
24; 9; 10 | — |
| PRIMARY Apparent Terminal Half-life (t1/2) for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Part C, D, and E) |
14.7; 15.9; 15.5 | — |
| PRIMARY Apparent Terminal Half-life (t1/2) for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Part F) |
16.2 | — |
| PRIMARY Number of Participants With an Adverse Event (AE) (Part 3) |
5; 8; 3 | — |
| PRIMARY Number of Participants Who Discontinued Treatment Due to an AE (Part 3) |
0; 0; 0 | — |
| PRIMARY Average Concentration (Cave) of MK-8521 Corresponding to Slope of Insulin Secretion Rate/Glucose (ISR/G) During Graded Glucose Infusion (GGI) at Tmax After a Single Dose of MK-8521 (Part 3) |
0.376; 1.64 | — |
| SECONDARY Change From Baseline in Time-weighted Average From 0 to 24 Hrs (TWA0-24hr) of Heart Rate (HR) After a Single Dose of MK-8521 (Part 1) |
6.67; 19.03; 0.06; 9.28; 7.99; 2.76 | — |
| SECONDARY Change From Baseline in TWA 0-24 Hrs. Semi-recumbent Systolic Blood Pressure (SBP) of Participants Treated With A Single Dose of MK-8521 (Part 1) |
-1.09; 8.43; -2.24; 3.18; 0.10; 0.78 | — |
| SECONDARY Change From Baseline in TWA 0-24 Hrs. Semi-recumbent Diastolic Blood Pressure (DBP) of Participants Treated With A Single Dose of MK-8521 (Part 1) |
0.30; 5.60; -3.73; -0.80; 2.54; -0.07 | — |
| SECONDARY Change From Baseline in TWA 0-24 Hrs. Heart Rate (HR) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel C, D, and E) |
1.18; 0.30; 4.15; -1.91; 4.24; 7.96 | — |
| SECONDARY Change From Baseline in TWA 0-24 Hrs. Heart Rate (HR) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F) |
0.14; 0.52; 5.22; 0.29; 9.25; -1.11 | — |
| SECONDARY Change From Baseline in TWA 0-24 Hrs. Semi-recumbent Systolic Blood Pressure (SBP) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panels C, D, and E) |
-0.12; 1.57; -2.65; 1.19; -2.08; -2.26 | — |
| SECONDARY Change From Baseline in TWA 0-24 Hrs. Semi-recumbent Systolic Blood Pressure (SBP) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F) |
-2.19; 1.82; -3.99; -6.55; -2.25; -9.43 | — |
| SECONDARY Change From Baseline in TWA 0-24 Hrs. Semi-recumbent Diastolic Blood Pressure (DBP) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Part C, D, and E) |
1.22; 2.38; 0.06; 0.25; 0.37; 2.63 | — |
| SECONDARY Change From Baseline in TWA 0-24 Hrs. Semi-recumbent Diastolic Blood Pressure (DBP) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F) |
-0.15; 1.45; 0.41; -2.63; 0.78; -3.19 | — |
| SECONDARY Slope of Insulin Secretion Rate/Glucose (ISR/G) During Graded Glucose Infusion (GGI) at Tmax After a Single Dose of MK-8521 (Part 3) |
0.0314; 0.0543; 0.0118 | <0.001 sig |
| SECONDARY Ratio of ISR/G at the Highest Glucose Infusion Rate During GGI Due to Treatment With A Single Dose of MK-8521 (Part 3) |
0.0164; 0.0256; 0.0084 | <0.001 sig |
| SECONDARY Glucose (TWA0-160min) During GGI at Tmax After a Single Dose of MK-8521 (Part 3) |
118.38; 95.73; 147.94 | <0.001 sig |
| SECONDARY Maximum Glycemic Excursion (Gmax) During GGI and Tmax After a Single Dose of MK-8521 (Part 3) |
154.37; 120.43; 217.53 | <0.001 sig |
| SECONDARY Area Under the Curve (AUC) 0-∞ for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 3) |
— | — |
| SECONDARY Area Under the Curve (AUC) 0-24hr. for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 3) |
— | — |
| SECONDARY Peak Plasma Concentration (Cmax) of Participants Treated With a Single Dose of MK-8521 (Part 3) |
0.418; 1.80 | — |
| SECONDARY Time Taken to Reach Cmax (Tmax) for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 3) |
11.8; 12.7 | — |
| SECONDARY Apparent Terminal Half-life (t1/2) for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 3) |
— | — |
Eligibility Criteria
Inclusion Criteria
- Males of either 18 to 45 or 45 to 70 years of age depending on the component of the study
- Body Mass Index between either 18-25 or 30-40 kg/m^2 depending on the component of the study
- Is in good health
- Is a non-smoker and/or has not used nicotine for at least 3 months
Exclusion Criteria
- Is mentally or legally incapacitated, has significant emotional problems or has a history of psychiatric disorders in the past 5 years
- Has a history of the following abnormalities or diseases: endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological.
- History of cancer
- History of significant multiple or severe allergies or has had an anaphylactic reaction or significant intolerability to drugs or food
- Positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV)
- Had major surgery, donated or lost 1 unit (500 mL) of blood or participated in another study within prior 4 weeks
- Has irritable bowel disease or recurrent nausea, vomiting, diarrhea or abdominal pain
- History of acute or chronic pancreatitis
- Uses 2 weeks prior to trial, or anticipates using during trial, medications, drugs or herbal remedies such as St. John's Wort
- Consumes greater than 3 glasses of alcohol per day
- Consumes greater than 6 servings of caffeinated beverages per day
- Regularly uses illicit drugs or has a history of drug (including alcohol) abuse within prior 3 months
- Has known hypersensitivity to glucagon or any glucagon like peptide 1 (GLP-1) receptor agonist
- Is unwilling/unable to consume standardized meals and/or is on a carbohydrate restricted diet
- Has history of hypersensitivity to pharmacologic insulins
Data sourced from ClinicalTrials.gov (NCT02055547). 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.