Detailed Description
This is a randomized, placebo-controlled, double-blind, double-dummy study to investigate the safety, tolerability, PK, and PD of subcutaneous (SC) doses of MET233 co-administered with MET097 in adult participants with a BMI of 27 to 45 kg/m2 (inclusive), including some participants with T2DM. For Part A, after the up to 4-week screening period, the study includes 1 dose and a 12-week safety follow-up after administration. For Part B and Part C, after the up to 4-week screening period, the study includes 12 once-weekly doses and an approximately 11-week safety follow-up after the last administration. Parts A and B will include only participants with overweight or obesity without type 2 diabetes. Part C will include participants with overweight or obesity who also have type 2 diabetes. For Part D, after the up to 4-week screening period, the study includes weekly and monthly (ie, every 4 weeks \[QM\]) and an approximate 11-week safety follow-up after last administration. For Part E, after the up to 4-week screening period, the study includes multiple dose QW-to-QM and an approximate 11-week safety followup after last administration. For Part G, after the up to 4-week screening period, the study includes multiple dose cohort of QW and QM and an approximate 11-week safety followup after last administration.
Eligibility Criteria
Age Range: 18 years to 75 years
Inclusion Criteria:
* Adult males or females aged 18 to 75 years (inclusive) at the time of screening.
* BMI ≥27.0 kg/m2 and ≤38.0 kg/m2 (inclusive) at Screening for Parts A, B, and C, and ≥30.0 kg/m2 and ≤45.0 kg/m2 (inclusive) at Screening for Parts D and E. Have a BMI ≥27.0 kg/m2 and ≤45.0 kg/m2 (inclusive) at Screening for Parts G.
* Participants must be in generally stable health, as determined by the investigator based on medical history, physical examination (including vital signs), laboratory evaluations, and electrocardiogram (ECG).
* Participants must have no clinically significant diseases or clinically significant findings on the physical examination (including vital signs), laboratory evaluations, and electrocardiogram (ECG).
* Participants in Parts C must not have clinically significant diseases except type 2 diabetes mellitus (T2DM), sleep apnea, well-controlled hypertension, and/or dyslipidemia.
* Participants in Parts E and G must not have any clinically significant diseases except hypertension, dyslipidemia, and/or a clinical diagnosis of sleep apnea.
* Willing and able to comply with all scheduled study visits, procedures, and required assessments.
* Women of childbearing potential must be willing to comply with protocol-specified contraceptive requirements and must not plan to become pregnant during the study.
Exclusion Criteria:
* Female who is lactating or who is pregnant according to the pregnancy test at Screening or on Day 1. Unwillingness or inability to comply with protocol-specified contraceptive requirements.
* Clinically significant abnormalities in laboratory results in the opinion of the investigator, increase risk or interfere with study participation.
* Seated blood pressure higher than 160/100 mmHg at the Screening visit or prior to the first study drug administration.
* Elevated resting pulse greater than 100 beats per minute at Screening visit or prior to the first study drug administration.
* Estimated glomerular filtration rate (eGFR) \<80 mL/min at the Screening visit.
* Diagnosis of Type 1 diabetes.
* For Part A, Part B, Part D, Part E and Part G: Diagnosis of T2DM or glycated hemoglobin (HbA1c) \> 6.4% or fasting plasma glucose \>126 mg/dL at the Screening visit or history of taking any medications to lower glucose.
* For Part A, Part B and Part D: Participant reported weight-related comorbidity, including sleep apnea and cardiovascular disease.
* Use of prohibited prescription or non-prescription medications, supplements, or investigational products within protocol-defined washout periods.
* History or presence of clinically significant gastrointestinal, endocrine, respiratory, renal, hepatic, hematologic, neurologic, cardiovascular, psychiatric, immunologic, or other systemic diseases, except where explicitly permitted by the protocol.
* Personal or family history of medullary thyroid carcinoma, multiple endocrine neoplasia syndrome, pancreatitis, or pancreatic cancer.
* History of acute or chronic pancreatitis or pancreatic cancer.
* Participation in a weight loss program with or without pharmacotherapy during the 3 months prior to study administration or plans to do so.
* History of bariatric or weight-loss surgery.
* Clinically significant psychiatric illness that may interfere with study participation or safety.
* Screening assessments indicative of moderate to severe depression.
* History of drug or alcohol abuse or dependence within the past 2 years.