Clinical trial NCT02055547
Conditions: Type 2 Diabetes Mellitus
Sponsor: Merck Sharp & Dohme LLC
Start date: 2013-05-10; Completion date: 2013-09-17
Enrollment: 61 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Detailed description:
This was a 3 part, randomized, single and multiple ascending-dose trial that evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of MK-8521 in healthy non-obese male (Part 1-Panels A and B, Panels C, D, and E of Part 2, and Part 3 Panel H) participants between the ages of 18 and 45 years and obese male participants (Part 2, Panel F) 45 to 65 years of age. An optional Panel G in Part 2 per protocol did not occur.

Part 1 was a single rising dose study to assess the safety and pharmacokinetics of single subcutaneous (SC) doses of MK-8521. Two panels of 8 healthy young non-obese male participants were dosed in up to 3 alternating dosing periods of MK-8521 or placebo (in a 6:2 ratio). Participants had a minimum 7 day washout between dosing periods.

Part 2 was a multiple-rising dose study to assess the safety and pharmacokinetics of multiple SC doses of MK-8521. Three panels (C-E) of 8 healthy young non-obese male participants received daily SC doses of MK-8521 or placebo (in a 6:2 ratio) as a titration regimen for 10 consecutive days. One panel (Panel F) of 8 older obese male participants received daily SC doses of MK-8521 or placebo (in a 6:2 ratio) as a titration regimen for 14 consecutive days.

Part 3 was a single dose, 3-period crossover study in 12 healthy lean male participants. Participants were randomized into 6 treatment groups and received a sequence of 3 treatments (MK-8521 at 35μg, 125μg and placebo). All participants in Part 3 received MK-8521 (high dose of 125μg and low dose of 35 μg) and placebo. There was a minimum 7 day washout between each dosing period for each individual participant.

Arms: arm 1: Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 100μg in the first treatment period, and matching placebo (PBO) in the second treatment period. There was a minimum of a 7-day washout period between treatment periods. arm 2: Healthy male participants of 18 to 45 years of age received a single dose of PBO in the first treatment period, and MK-8521 300μg in the second treatment period. There was a minimum of a 7-day washout period between treatment periods. arm 3: Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 100μg in the first treatment period, and MK-8521 300μg in the second treatment period. There was a minimum of a 7-day washout period between treatment periods. arm 4: Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 150μg in the first treatment period, PBO in the second treatment period, and MK-8521 175μg in the third treatment period. There was a minimum of a 7-day washout period between treatment periods. arm 5: Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 150μg in the first treatment period, MK-8521 200μg in the second treatment period, and MK-8521 175μg in the third treatment period. There was a minimum of a 7-day washout period between treatment periods. arm 6: Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 150μg in the first treatment period, MK-8521 200μg in the second treatment period, and PBO in the third treatment period. There was a minimum of a 7-day washout period between treatment periods. arm 7: Healthy male participants of 18 to 45 years of age received PBO in the first treatment period, MK-8521 200μg in the second treatment period, and MK-8521 175μg in the third treatment period. There was a minimum of a 7-day washout period between treatment periods. arm 8: Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 50μg Days 1 to 5 and MK-8521 72μg Days 6 to 10 in a single treatment period. arm 9: Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 100μg Days 1 to 5 and MK-8521 150μg Days 6 to 10 in a single treatment period. arm 10: Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 125μg Days 1 to 5 and MK-8521 150μg Days 6 to 10 in a single treatment period. arm 11: Obese male participants of 45 to 65 years of age received a single dose of MK-8521 72μg Days 1 to 7 and MK-8521 125μg Days 8 to 14 in a single treatment period. arm 12: Healthy male participants of 18 to 45 years of age received PBO once daily for 10 days. arm 13: Obese male participants of 45 to 65 years of age received a single dose of PBO Days 1 to 14. arm 14: Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 125μg (high dose) in the first treatment period, MK-8521 35μg (low dose) in the second treatment period, and PBO in the third treatment period. There was a minimum of a 7-day washout period between treatment periods. arm 15: Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 35μg (low dose) in the first treatment period, PBO MK-8521 in the second treatment period, and 125μg (high dose) in the third treatment period. There was a minimum of a 7-day washout period between treatment periods. arm 16: Healthy male participants of 18 to 45 years of age received a single dose of PBO in the first treatment period, MK- 8521 125μg (high dose) in the second treatment period, and MK-8521 35μg (low dose) in the third treatment period. There was a minimum of a 7-day washout period between treatment periods. arm 17: Healthy male participants of 18 to 45 years of age received a single dose of PBO in the first treatment period, MK- 8521 35μg (low dose) in the second treatment period, and MK-8521 125μg (high dose) in the third treatment period. There was a minimum of a 7-day washout period between treatment periods. arm 18: Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 125μg (high dose) in the first treatment period, PBO in the second treatment period, and MK-8521 35μg (low dose) in the third treatment period. There was a minimum of a 7-day washout period between treatment periods. arm 19: Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 35μg (low dose) in the first treatment period, MK-8521 125μg (high dose) in the second treatment period, and PBO in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Interventions: intervention 1: MK-8521 35μg intervention 2: MK-8521 100μg intervention 3: MK-8521 125μg intervention 4: MK-8521 150μg intervention 5: MK-8521 175μg intervention 6: MK-8521 200μg intervention 7: MK-8521 300μg intervention 8: MK-8521 50/72μg intervention 9: MK-8521 72/125μg intervention 10: MK-8521 100/150μg intervention 11: MK-8521 125/150μg intervention 12: Placebo
Intervention descriptions: intervention 1: Single dose 35μg subcutaneous (SC) injection in a treatment period (Part 3, Panel H) intervention 2: Single dose 100μg SC injection in a treatment period (Part 1, Panel A) and (Part 2, Panel D) intervention 3: Single dose 125μg SC injection in a treatment period (Part 2, Panel E) and (Part 3, Panel H) intervention 4: Single dose 150μg SC injection in a treatment period (Part 1, Panel B) intervention 5: Single dose 175μg SC injection in a treatment period (Part 1, Panel B) intervention 6: Single dose MK-8521 200μg SC injection in a treatment period (Part 1, Panel B) intervention 7: Single dose 300μg SC injection in a treatment period (Part 1, Panel A) intervention 8: MK-8521 50μg SC injection Days 1-5 and 72μg Days 6-10 (Part 2, Panel C) intervention 9: MK-8521 72μg SC injection Days 1-7 and 125μg Days 8-14 (Part 2, Panel F) intervention 10: MK-8521 100μg SC injection Days 1-5 and 150μg Days 6-10 SC in a treatment period (Part 2, Panel D) intervention 11: MK-8521 SC 125μg SC injection Days 1-5 and 150μg Days 6-10 (Part 2, Panel E) intervention 12: Placebo to MK-8521 SC injection in a treatment period (Parts 1, 2, and 3)

Protocol documents: