A 2-part, Phase 1b Clinical Study Designed to Evaluate the Safety, PK, and Efficacy of CRB-913 in Participants With Obesity

Exclusion Criteria

• •Significant liver disease or moderate-severe hepatic impairment
• •History of seizures, epilepsy, or intracranial surgery
• •Diabetes mellitus (Type 1 or Type 2), except gestational
• •Bariatric surgery or \>5 kg weight change in past 3 months
• •Recent use (within 3 months) of GLP-1 agonists or other weight-loss medications
• •Major depression within 2 years.
• •Any history of suicidal ideation/attempt
• •Severe psychiatric disorders (e.g., schizophrenia, bipolar disorder)
• •Elevated screening scores: PHQ-9 \>4, GAD-7 \>4, or positive C-SSRS Items 1-2
• •Active or recent (within 5 years) malignancy (exceptions: in situ and fully resected nonmelanoma skin cancer)
• •Abnormal thyroid function: TSH \>6 mIU/L unless stable on replacement therapy
• •QTc \>470 msec (females) or \>450 msec (males) or history of long QT syndrome
• •Use of systemic corticosteroids or unstable chronic medications affecting BP, lipids, or glucose
• •Use of CYP3A4 substrates or strong P-gp substrates/inhibitors
• •Investigational drug use within 28 days
• •Prior exposure to CRB-913 or other CB1 inverse agonists/antagonists
• •Substance abuse history
• •Pregnancy, breastfeeding, or unwillingness to use highly effective contraception
• •Positive drug or alcohol screen
• •Any condition that, in the investigator's judgment, makes participation unsafe or non-feasible