A Single and Multiple-Dose Study of MK-8521 in Healthy and Obese Males (MK-8521-002)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): MK-8521 35μg; MK-8521 100μg; MK-8521 125μg; MK-8521 150μg; MK-8521 175μg; MK-8521 200μg; MK-8521 300μg; MK-8521 50/72μg; MK-8521 72/125μg; MK-8521 100/150μg; MK-8521 125/150μg; Placebo
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Single dose 35μg subcutaneous (SC) injection in a treatment period (Part 3, Panel H); Single dose 100μg SC injection in a treatment period (Part 1, Panel A) and (Part 2, Panel D); Single dose 125μg SC injection in a treatment period (Part 2, Panel E) and (Part 3, Panel H); Single dose 150μg SC injection in a treatment period (Part 1, Panel B); Single dose 175μg SC injection in a treatment period (Part 1, Panel B); Single dose MK-8521 200μg SC injection in a treatment period (Part 1, Panel B); Single dose 300μg SC injection in a treatment period (Part 1, Panel A); MK-8521 50μg SC injection Days 1-5 and 72μg Days 6-10 (Part 2, Panel C); MK-8521 72μg SC injection Days 1-7 and 125μg Days 8-14 (Part 2, Panel F); MK-8521 100μg SC injection Days 1-5 and 150μg Days 6-10 SC in a treatment period (Part 2, Panel D); MK-8521 SC 125μg SC injection Days 1-5 and 150μg Days 6-10 (Part 2, Panel E); Placebo to MK-8521 SC injection in a treatment period (Parts 1, 2, and 3)
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Parts 1 and 2 were parallel in design and Part 3 was crossover in design.
Masking: Double (Participant, Investigator)
Primary purpose: Treatment