Obese But Otherwise Healthy Participants
Conditions
Keywords
Obesity, Body Weight, Nutritional and Metabolic Diseases, Metabolic Diseases, Endocrine System Diseases, Overweight, Nutrition Disorders, Cannabinoid-1 receptor inverse agonist
Brief summary
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.
Detailed 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.
Interventions
DRUGCRB-913
Administered QD
DRUGPlacebo
Administered QD
Sponsors
Corbus Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Part 1 is open label. Part 2 is double blind.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: To evaluate the PK of a single dose of CRB-913 - Cmax | 0 to 48 hours | Maximum plasma concentration (Cmax) |
| Part 1: To evaluate the PK of a single dose of CRB-913 - Tmax | 0 to 48 hours | Time to maximum plasma concentration (Tmax) |
| Part 1: To evaluate the PK of a single dose of CRB-913 - T1/2 | 0 to 48 hours | Terminal elimination half-life (T1/2) |
| Part 2: To evaluate the safety of CRB-913 - TEAE | Day 1 to 28 days post final dose | Incidence and severity of treatment emergent adverse events |
| Part 2: To evaluate the safety of CRB-913 - AESI | Day 1 to 28 days post final dose | Incidence of adverse events of special interest |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: To evaluate the safety of a single dose of CRB-913 - TEAE | Day 1 to 28 days post final dose | Incidence and severity of treatment emergent adverse events |
| Part 2: To evaluate the effect of CRB-913 on weight | Day 1 to 28 days post final dose | Mean change in absolute body weight from baseline to End of Treatment (EOT) compared to placebo |
| Part 2: To evaluate the PK of CRB-913 - Cmax | Day 1 to 28 days post final dose | Maximum plasma concentration (Cmax) |
| Part 2: To evaluate the PK of CRB-913 - Tmax | Day 1 to 28 days post final dose | Time to maximum plasma concentration (Tmax) |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORLeela Vrishabhendra, MD
Medpace Clinical Pharmacology
Outcome results
None listed