Overview
This study will assess the safety of the investigational drug CRB-913 and how it is processed in the body.
The study has two parts: Part 1 will measure drug levels in healthy adults after taking CRB-913 tablets, and Part 2 will compare three doses of CRB-913 with placebo to evaluate safety, effects on body weight, and drug levels in the blood.
Part 2 is blinded, meaning participants, study doctors, and the sponsor will not know which treatment is given.
Participants in Part 2 will take study treatment for 12 weeks and will be followed for 28 days after treatment ends.
Description
CRB-913 is a novel cannabinoid receptor type 1 (CB1) inverse agonist (CB1-IA) that is being developed for once-daily treatment of obesity.
This study will look at how the investigational drug CRB-913 behaves in the body and how it affects body weight.
The study has two parts:
Part 1 will include healthy adult participants. They will receive CRB-913 in tablet form. Researchers will measure how much of the drug enters the bloodstream and how long it stays there.
Part 2 will include participants who will receive one of three different doses of CRB-913 or a placebo (a tablet with no active drug). This part of the study will look at the safety of CRB-913 and its effects on body weight. Researchers will also measure the amount of CRB-913 in the blood.
Part 2 is blinded, which means that participants, study doctors, and the study sponsor will not know who is receiving CRB-913 or placebo.
All participants in Part 2 will take their assigned study tablets for 12 weeks, followed by a 28-day follow-up period after treatment ends.
The information collected in this study will help determine whether CRB-913 is safe, how the body processes it, and whether it may help with weight-related outcomes.
Eligibility
Inclusion Criteria:
- Part 1: Participants with BMI 18.0-25.0 kg/m²
- Part 2: Obese participants with BMI ≥30 kg/m²
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