A Phase 1b/2 Randomized, Double-Blind, Placebo-Controlled, Ascending-Dose Study of BXCL501 to Treat Symptoms of Acute Opioid Withdrawal in Patients With Opioid Use Disorder Who Are Physically Dependent on Opioids

BXCL501-201

This Phase 1b/2 inpatient study assessed the safety, pharmacokinetics, and early signs of efficacy of escalating doses of BXCL501 versus placebo following discontinuation of morphine maintenance. The opioid (morphine) maintenance phase (Phase 1b) included Days 1-5; the randomized BXCL501/placebo phase (Phase 2) included Days 6-12. The randomized phase was followed by 2 sequential days, Days 13 and 14, utilizing treatment of BXCL501-placebo sublingual films and morphine-placebo capsules for all subjects who remained in the study.

2020-06-09

2021-02-18

2021-02-18

Completed

Early phase I

225

Inclusion Criteria 1. Male and female subjects who are 18 years of age to less than 65 years of age. 2. Meets criteria for moderate to severe opioid use disorder as per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria and confirmed by the Mini International Neuropsychiatric Interview (MINI) with physiological dependence as evidenced by a Clinical Opiate Withdrawal (COWS) score of \>5 or a positive naloxone challenge upon admission on Day 1. 3. Subjects who can read, understand, and provide written informed consent. Women of childbearing potential must have a negative pregnancy test and agree to be abstinent or use an acceptable method of contraception for the duration of the study. Exclusion Criteria 1. Positive urine pregnancy test at screening or when tested or currently breast feeding. 2. Clinically significant history of cardiac disease, screening and baseline heart rate of \<55 beats per minutes or systolic blood pressure \<110 mmHg or diastolic blood pressure \<70 mmHg. 3. History or presence of a significant medical disease or disorder which, in the opinion of the investigator, increases the risk or may confound the interpretation of study measures, as confirmed by screening laboratory results. 4. Hepatic dysfunction (marked by ascites, or bilirubin \>10% above the upper limit of normal \[ULN\] or liver function tests \>3 x ULN) at the screening visit. 5. Acute active Hepatitis B or C as evidenced by positive serology and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \>2 x ULN. 6. Clinically significant abnormal ECG findings such as second- or third-degree heart block, uncontrolled arrhythmia, or QTcF (Fridericia correction formula) interval \>450 msec for males, and \>470 msec for females at screening or prior to dosing. 7. Any psychiatric disorder that would compromise ability to complete study requirements. 8. Currently meets DSM-5 criteria for substance abuse disorder, moderate or severe for any substance other than opioids, caffeine, or nicotine and/or current physical dependence on drugs that pose risk of withdrawal that requires medical management such as alcohol or benzodiazepines. 9. History of suicidal behavior within the last 1 year prior to screening. 10. Participation in a clinical trial of a non-FDA-approved pharmacological agent within 30 days prior to screening. 11. Use of any excluded medication at screening or anticipated/required use during the study period. 12. Subjects with a history of intolerance to morphine. 13. Any finding that, in the view of the principal investigator, would compromise the subject's ability to fulfill the protocol visit schedule or visit requirements.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'Phase 1b: The blinded opioid maintenance phase (Days 1 to 5). Doses of morphine during Phase 1b varied at the discretion of the investigator, between 120-150 mg per day, depending on patients abuse history and need for a higher dose to stabilize withdrawal symptoms. In addition to morphine maintenance, all subjects received sublingual placebo films, approximately 12 hours apart, at 8 am and 8 pm (30min) during this period to simulate and thus blind treatment to BXCL501 sublingual films during Days 6 to 12 (Phase 2).\n\nPhase 2: The randomized BXCL501/placebo phase (both active and placebo administered as sublingual films) occurred on Days 6 to 12, followed by 2 days of BXCL501-placebo sublingual film and morphine-placebo capsule treatment for all remaining subjects on Days 13 and 14 following the dosing timeline as administered in the Phase 1b portion of the study.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'maskingDescription': 'Phase 1b: morphine maintenance, blinded to BXCL501 sublingual treatment (placebo).\n\nPhase 2: Randomized, Double-blind, placebo-controlled (4:1, active to placebo ratio, respectively).\n\nFollow-On portion of Phase 2: Double-blind, placebo-controlled (treatment with morphine-placebo capsules and BXCL501-placebo sublingual films as administered during phase 1b)', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 225, 'type': 'ACTUAL'}}

2023-10-26