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A Single and Multiple-Dose Study of MK-8521 in Healthy and Obese Males (MK-8521-002)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02055547
Recruitment Status : Completed
First Posted : February 5, 2014
Last Update Posted : August 24, 2016
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of MK-8521. The primary hypothesis is that MK-8521 is sufficiently safe and well-tolerated in healthy, lean and obese males.

Condition or disease Intervention/treatment Phase
Type II Diabetes Mellitus Drug: MK-8521 Drug: Mk-8521 Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Single and Multiple-Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8521 in Subjects
Study Start Date : May 2013
Actual Primary Completion Date : September 2013
Actual Study Completion Date : September 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 100 - PBO (Part1)
Participants received a single dose of 100 micrograms (mcg) subcutaneous (sc) MK-8521 in the first treatment period, and Placebo (PBO) in the second period, with a 7-day washout between each period
Drug: MK-8521
Single dose 100 mcg sc injection in a treatment period (Part 1)

Drug: Placebo
Single dose placebo sc injection in a treatment period (Part 1)

Experimental: PBO - 300 (Part 1)
Participants received a single dose sc PBO in the first treatment period, and 300 mcg MK-8521 in the second period, with a 7-day washout between each period
Drug: MK-8521
Single dose 300 mcg sc injection in a treatment period (Part 1)

Drug: Placebo
Single dose placebo sc injection in a treatment period (Part 1)

Experimental: 100 - 300 (Part 1)
Participants received a single dose sc 100 mcg MK-8521 in the first treatment period, and 300 mcg MK-8521 in the second period, with a 7-day washout between each period
Drug: MK-8521
Single dose 100 mcg sc injection in a treatment period (Part 1)

Drug: MK-8521
Single dose 300 mcg sc injection in a treatment period (Part 1)

Experimental: 150 - PBO - 175 (Part 1)
Participants received a single dose sc 150 mcg MK-8521 in the first treatment period, PBO in the second period, and 175 mcg MK-8521 in the third period, with a 7-day washout between each period
Drug: MK-8521
Single dose 150 mcg sc injection in a treatment period (Part 1)

Drug: Mk-8521
Single dose 175 mcg sc injection in a treatment period (Part 1)

Drug: Placebo
Single dose placebo sc injection in a treatment period (Part 1)

Experimental: 150 - 200 - 175 (Part 1)
Participants received a single dose sc 150 mcg MK-8521 in the first treatment period, 200 mcg MK-8521 in the second period, and 175 mcg MK-8521 in the third period, with a 7-day washout between each period
Drug: MK-8521
Single dose 150 mcg sc injection in a treatment period (Part 1)

Drug: MK-8521
Single dose 200 mcg sc injection in a treatment period (Part 1)

Drug: Mk-8521
Single dose 175 mcg sc injection in a treatment period (Part 1)

Experimental: 150 - 200 - PBO (Part 1)
Participants received a single dose sc 150 mcg MK-8521 in the first treatment period, 200 mcg MK-8521 in the second period, and PBO in the third period, with a 7-day washout between each period
Drug: MK-8521
Single dose 150 mcg sc injection in a treatment period (Part 1)

Drug: MK-8521
Single dose 200 mcg sc injection in a treatment period (Part 1)

Drug: Placebo
Single dose placebo sc injection in a treatment period (Part 1)

Experimental: PBO - 200 - 175 (Part 1)
Participants received a single dose sc PBO in the first treatment period, 200 mcg MK-8521 in the second period, and 175 mcg MK-8521 in the third period, with a 7-day washout between each period
Drug: MK-8521
Single dose 200 mcg sc injection in a treatment period (Part 1)

Drug: Mk-8521
Single dose 175 mcg sc injection in a treatment period (Part 1)

Drug: Placebo
Single dose placebo sc injection in a treatment period (Part 1)

Experimental: 50 - 74 (10 Days) (Part 2)
Once daily dose of sc MK-8521 over 10 days: 50 mcg Days 1-5, 74 mcg Days 6-10
Drug: MK-8521
50 mcg sc injection once each day for 5 days (Part 2)

Drug: MK-8521
74 mcg sc injection once each day for 5 days (Part 2)

Experimental: 100 - 150 (10 Days) (Part 2)
Once daily dose of sc MK-8521 over 10 days: 100 mcg Days 1-5, 150 mcg Days 6-10
Drug: MK-8521
100 mcg sc injection once each day for 5 days (Part 2)

Drug: MK-8521
150 mcg sc injection once each day for 5 days (Part 2)

Experimental: 125 - 150 (10 Days) (Part 2)
Once daily dose of sc MK-8521 over 10 days: 125 mcg Days 1-5, 150 mcg Days 6-10
Drug: MK-8521
125 mcg sc injection once each day for 5 days (Part 2)

Drug: MK-8521
150 mcg sc injection once each day for 5 days (Part 2)

Experimental: 72 - 125 (14 Days) (Part 2)
Once daily dose of sc MK-8521 over 14 days in older and obese participants: 72 mcg Days 1-7, 125 mcg Days 8-14
Drug: MK-8521
72 mcg sc injection once each day for 7 days (Part 2)

Drug: MK-8521
125 mcg sc injection once each day for 7 days (Part 2)

Placebo Comparator: PBO (10 Days) (Part 2)
Placebo for sc MK-8521 once daily over 10 days
Drug: Placebo
Placebo sc injection once each day for 10 days (Part 2)

Placebo Comparator: PBO (14 Days) (Part 2)
Placebo for sc MK-8521 once daily over 14 days
Drug: Placebo
Placebo sc injection once each day for 14 days (Part 2)

Experimental: High-PBO-Low (Part 3)
Participants received a single dose sc high dose MK-8521 in the first treatment period, PBO in the second period, and low dose MK-8521 in the third period, with a 7-day washout between each period
Drug: MK-8521
Single low dose sc injection in a treatment period (Part 3)

Drug: MK-8521
Single high dose sc injection in a treatment period (Part 3)

Drug: Placebo
Single Placebo sc injection in a treatment period (Part 3)

Experimental: Low-High-PBO (Part 3)
Participants received a single dose sc low dose MK-8521 in the first treatment period, high dose MK-8521 in the second period, and PBO in the third period, with a 7-day washout between each period
Drug: MK-8521
Single low dose sc injection in a treatment period (Part 3)

Drug: MK-8521
Single high dose sc injection in a treatment period (Part 3)

Drug: Placebo
Single Placebo sc injection in a treatment period (Part 3)

Experimental: Low-PBO-High (Part 3)
Participants received a single dose sc low dose MK-8521 in the first treatment period, PBO in the second period, and high dose MK-8521 in the third period, with a 7-day washout between each period
Drug: MK-8521
Single low dose sc injection in a treatment period (Part 3)

Drug: MK-8521
Single high dose sc injection in a treatment period (Part 3)

Drug: Placebo
Single Placebo sc injection in a treatment period (Part 3)

Experimental: PBO-High-Low (Part 3)
Participants received a single dose sc PBO in the first treatment period, high dose MK-8521 in the second period, and low dose MK-8521 in the third period, with a 7-day washout between each period
Drug: MK-8521
Single low dose sc injection in a treatment period (Part 3)

Drug: MK-8521
Single high dose sc injection in a treatment period (Part 3)

Drug: Placebo
Single Placebo sc injection in a treatment period (Part 3)

Experimental: PBO-Low-High (Part 3)
Participants received a single dose sc PBO in the first treatment period, low dose MK-8521 in the second period, and high dose MK-8521 in the third period, with a 7-day washout between each period
Drug: MK-8521
Single low dose sc injection in a treatment period (Part 3)

Drug: MK-8521
Single high dose sc injection in a treatment period (Part 3)

Drug: Placebo
Single Placebo sc injection in a treatment period (Part 3)

Experimental: High-Low-PBO (Part 3)
Participants received a single dose sc high dose MK-8521 in the first treatment period, low dose MK-8521 in the second period, and PBO in the third period, with a 7-day washout between each period
Drug: MK-8521
Single low dose sc injection in a treatment period (Part 3)

Drug: MK-8521
Single high dose sc injection in a treatment period (Part 3)

Drug: Placebo
Single Placebo sc injection in a treatment period (Part 3)




Primary Outcome Measures :
  1. Number of participants with an adverse event (AE) (Part 1) [ Time Frame: Up to Day 34 ]
  2. Number of participants who discontinued treatment due to an AE (Part 1) [ Time Frame: Day 1 ]
  3. Area under the curve (AUC) 0-∞ for plasma concentration of participants treated with a single dose of MK-8521 (Part 1) [ Time Frame: Up to Day 6 ]
  4. Peak plasma concentration (Cmax) of participants treated with a single dose of MK-8521 (Part 1) [ Time Frame: Up to Day 6 ]
  5. Time taken to reach Cmax (Tmax) for plasma concentration of participants treated with a single dose of MK-8521 (Part 1) [ Time Frame: Up to Day 6 ]
  6. Apparent terminal half-life (T 1/2) for plasma concentration of participants treated with a single dose of MK-8521 (Part 1) [ Time Frame: Up to Day 6 ]
  7. Number of participants with an AE (Part 2) [ Time Frame: Up to Day 43 ]
  8. Number of participants who discontinued treatment due to an AE (Part 2) [ Time Frame: Up to Day 14 ]
  9. AUC 0-24hr for plasma concentration of participants treated with multiple doses of MK-8521 (Part 2) [ Time Frame: Up to Day 19 ]
  10. Cmax for plasma concentration of participants treated with multiple doses of MK-8521(Part 2) [ Time Frame: Up to Day 19 ]
  11. Trough plasma concentration (Ctrough) of participants treated with multiple doses of MK-8521(Part 2) [ Time Frame: Up to Day 19 ]
  12. Tmax for plasma concentration of participants treated with multiple doses of MK-8521 (Part 2) [ Time Frame: Up to Day 19 ]
  13. T 1/2 for plasma concentration of participants treated with multiple doses of MK-8521 (Part 2) [ Time Frame: Up to Day 19 ]
  14. Number of participants with an AE (Part 3) [ Time Frame: Up to Day 43 ]
  15. Number of participants who discontinued treatment due to an AE (Part 3) [ Time Frame: Up to Day 14 ]
  16. Slope of insulin secretion rate/glucose (ISR/G) during graded glucose infusion (GGI) due to treatment with a single dose of MK-8521 (Part 3) [ Time Frame: Day 1 ]

Secondary Outcome Measures :
  1. Change from baseline in time-weighted average (TWA) 0-24 hrs heart rate of participants treated with a single dose of MK-8521 (Part 1) [ Time Frame: Day 1 pre-dose and through Day 2 after dosing ]
  2. Change from baseline in TWA 0-24 hrs systolic blood pressure (BP) of participants treated with a single dose of MK-8521 (Part 1) [ Time Frame: Day 1 pre-dose and through Day 2 after dosing ]
  3. Change from baseline in TWA 0-24 hrs diastoliic BP of participants treated with a single dose of MK-8521 (Part 1) [ Time Frame: Day 1 pre-dose and through Day 2 after dosing ]
  4. Change from baseline in TWA 0-24 hrs heart rate of participants treated with multiple doses of MK-8521 (Part 2) [ Time Frame: Day (-1) and up to Day 14 ]
  5. Change from baseline in TWA 0-24 hrs systolic BP of participants treated with multiple doses of MK-8521 (Part 2) [ Time Frame: Day (-1) and up to Day 14 ]
  6. Change from baseline in TWA 0-24 hrs diastolic BP of participants treated with multiple doses of MK-8521 (Part 2) [ Time Frame: Day (-1) and up to Day 14 ]
  7. Glucose (TWA 0-160 min) during GGI at Tmax due to treatment with a single dose of MK-8521 (Part 3) [ Time Frame: Day 1 ]
  8. Maximum glycemic excursion (Gmax) during GGI at Tmax due to treatment with a single dose of MK-8521 (Part 3) [ Time Frame: Day 1 ]
  9. Ratio of ISR/G at the highest glucose infusion rate during GGI due to treatment with a single dose of MK-8521 (Part 3) [ Time Frame: Day 1 ]
  10. AUC 0-∞ for plasma concentration of participants treated with a single dose of MK-8521 (Part 3) [ Time Frame: Day 1 ]
  11. Cmax for plasma concentration of participants treated with a single dose of MK-8521 (Part 3) [ Time Frame: Day 1 ]
  12. Tmax for plasma concentration of participants treated with a single dose of MK-8521 (Part 3) [ Time Frame: Day 1 ]
  13. T 1/2 for plasma concentration of participants treated with a single dose of MK-8521 (Part 3) [ Time Frame: Day 1 ]
  14. Slope of (ISR/G) during GGI at Tmax due to treatment with a single dose of MK-8521 (Part 3) [ Time Frame: Day 1 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02055547    
Other Study ID Numbers: 8521-002
2013-000083-28 ( EudraCT Number )
First Posted: February 5, 2014    Key Record Dates
Last Update Posted: August 24, 2016
Last Verified: August 2016
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases