a single and multiple-dose study of mk-8521 in healthy and obese males (mk-8521-002)

Conditions: Type 2 Diabetes Mellitus

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.

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.

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