The goal of this clinical trial is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of once-weekly subcutaneous injections of MET233 in otherwise healthy adults with overweight or obesity. This study will be conducted in four parts: * Part A will evaluate single ascending doses of MET233 or placebo. * Part B will evaluate multiple ascending doses, with participants receiving five once-weekly doses of MET233 or placebo. * Part C will evaluate once-weekly dosing of MET233 or placebo for 12 weeks, followed by a single higher, potential monthly dose. * Part D will evaluate a longer dosing schedule, in which participants will receive twelve once-weekly doses, followed by three monthly doses of MET233 or placebo. Participants in this part will be followed for 14 weeks after the final dose.
This is a randomized, placebo-controlled, double-blind study designed to investigate the safety, tolerability, PK and pharmacodynamic (PD) of single and multiple ascending subcutaneous (SC) doses of MET233 in otherwise healthy adult participants with obesity or overweight (body mass index \[BMI\] 27.0 kg/m2 to 38.0 kg/m2, inclusive for Parts A-C and BMI in Part D 30- 45.0 kg/m2 (inclusive). * In Part A, participants will receive a single dose of MET233 at up to five dose levels. * In Part B, participants will receive five weekly doses of MET233 at up to four dose levels. * In Part C, participants will receive 12 weekly doses of MET233. These doses may include titration. For all cohorts in Part C, a 13th dose administered on Day 85 may be a monthly-equivalent dose to evaluate the potential for switching to a monthly dosing regimen. * In Part D, participants will receive 12 once-weekly doses, followed by three monthly doses of MET233 or placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
144
Altasciences Clinical Los Angeles, Inc.
Cypress, California, United States
Occurrence of Treatment Emergent Adverse Events
Time frame: Part A (Baseline to Day 85), Part B (Baseline to Day 113), Part C (Baseline to Day 162), Part D (Baseline to Day 239)
Area under the concentration versus time curve extrapolated to infinity (AUCinf)
Time frame: Part A (Baseline to Day 85)
Area under the concentration versus time curve during the dosing interval (AUCtau)
Time frame: Part B (Baseline to Day 113), Part C (Baseline to Day 162), Part D (Baseline to Day 239)
Maximum observed concentration (Cmax)
Time frame: Part A (Baseline to Day 85), Part B (Baseline to Day 113), Part C (Baseline to Day 162), Part D (Baseline to Day 239)
Time to maximum observed concentration (Tmax)
Time frame: Part A (Baseline to Day 85), Part B (Baseline to Day 113), Part C (Baseline to Day 162), Part D (Baseline to Day 239)
Elimination half-life (t1/2)
Time frame: Part A (Baseline to Day 85), Part B (Baseline to Day 113), Part C (Baseline to Day 162), Part D (Baseline to Day 239)
Percent change from baseline in body weight at the protocol-specified weekly post-baseline measurements
Time frame: Part A (Baseline to Day 85), Part B (Baseline to Day 113), Part C (Baseline to Day 162), Part D (Baseline to Day 239)
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