A Pilot Study to Evaluate the Efficacy, Safety and Tolerability of BMS-986368, a FAAH/MAGL Inhibitor, in Participants With Post-Stroke Spasticity (The STIPS Study)

A Phase 2, Randomized, Double-blind, Placebo-controlled Pilot Study Assessing the Efficacy, Safety and Tolerability of Orally Administered BMS-986368, a FAAH/MAGL Inhibitor, for the Treatment of Spasticity in Participants With Post-stroke Spasticity

The goal of this clinical trial is to learn if the drug BMS-986368 works to treat post stroke spasticity in adults who have had a stroke. BMS-986368 is a designed to increase natural compounds in the body that may help calm nerves that cause muscles to be tight or spasm. The study will also learn about the safety of drug BMS-986368

Post-stroke spasticity (PSS) is a common and disabling complication of stroke that can impair upper-limb function, limit activities of daily living, and negatively affect quality of life. Current treatment options, including oral antispasticity medications and botulinum toxin injections, may provide incomplete symptom control and are often associated with tolerability limitations. Therefore, there is a need for novel therapies that can improve both spasticity and functional recovery in individuals with PSS. Preclinical evidence and early clinical experience support evaluation of BMS-986368 as a treatment for post-stroke spasticity. The STIPS Study is a Phase 2, randomized, double-blind, placebo-controlled pilot trial designed to evaluate the efficacy, safety, and tolerability of BMS-986368 in adults with post-stroke spasticity. The study consists of:

• A screening period of up to 4 weeks
• An 8-week double-blind treatment period
• An optional 8-week double-blind active treatment extension (DBATE)
• A 4-week safety follow-up period The maximum study duration is approximately 24 weeks. During the double-blind treatment period, participants randomized to active treatment will receive oral BMS-986368 with dose escalation from 1 mg once daily, to 3 mg once daily and then 6 mg once daily. Participants randomized to placebo will receive matching placebo capsules. Participants who complete the double-blind treatment period may elect to enter the DBATE, during which all participants receive active treatment while maintaining study blinding. The study hypothesis is that BMS-986368 administered up to 6 mg once daily will result in greater improvement in spasticity and upper-extremity motor function compared with placebo, while demonstrating an acceptable safety and tolerability profile in participants with post-stroke spasticity

Inclusion Criteria:

• Ischemic or hemorrhagic stroke diagnosis 4 to 18 months prior to enrollment.
• History of post stroke spasticity for at least 2 months prior to Screening Visit.
• Modified Ashworth Scale (mAS) score ≥2 and <4 for affected elbow and wrist joints at Screen and Baseline Visits.
• Fugl-Meyer Assessment for Upper Extremity (FMA-UE) greater than 22 at Screen and Baseline Visits
• Willing to participate with no therapy additions during study duration.
• Participant must be able to read, speak, and understand English usage

Exclusion Criteria:

Individuals who are pregnant or breastfeeding.

• Participants must not have any concomitant disease or disorder that has symptoms of spasticity or that may influence the participant's level of spasticity.
• Participants must not have a history of any substance abuse disorder as defined in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Diagnostic Criteria for Drug and Alcohol Abuse.
• Participants must not be currently taking a medication for spasticity that cannot be discontinued and washed out prior to randomization.
• Participants must not have used FAAH/MAGL inhibitor medication or any cannabinoid-related products (including cannabis, cannabidiol (CBD), or tetrahydrocannabinol (THC)) within 30 days prior to randomization.
• Other protocol-defined Inclusion/Exclusion criteria apply.