Cooperative Agreement U01DA060708

PHASE III DOUBLE-BLIND, RANDOMIZED CONTROLLED TRIAL OF SUVOREXANT VERSUS PLACEBO TO TREAT INSOMNIA IN PERSONS WITH OPIOID USE DISORDER - OPIOID USE DISORDER (OUD) IS A RAPIDLY ESCALATING PUBLIC HEALTH CRISIS WITH RECENT EVIDENCE SUGGESTING THAT CLOSE TO 70% OF DRUG OVERDOSE DEATHS INVOLVED OPIOIDS IN THE LAST YEAR. MEDICATIONS FOR OUD (MOUDS) SUCH AS BUPRENORPHINE AND METHADONE ARE THE FRONTLINE TREATMENT FOR OUD, YET OVER HALF OF INDIVIDUALS WHO INITIATE MOUD RELAPSE OR LEAVE TREATMENT IN THE FIRST YEAR, HIGHLIGHTING THE IMPORTANCE OF ADJUNCTIVE THERAPIES THAT MIGHT IMPROVE OUD TREATMENT OUTCOMES. INSOMNIA IS A COMMON AND OFTEN RECALCITRANT ISSUE AMONG PERSONS ON MOUDS BUT THERE IS LITTLE GUIDANCE ON HOW TO AMELIORATE SYMPTOMS OF INSOMNIA DURING OUD TREATMENT. THE OREXIN (OR HYPOCRETIN) NEUROTRANSMITTER SYSTEM PLAYS A ROLE IN INSOMNIA AND IN THE ONSET, PROGRESSION, AND MAINTENANCE OF OUD. SUVOREXANT IS A DUAL-OREXIN RECEPTOR ANTAGONISTS THAT IS FDA-APPROVED FOR THE TREATMENT OF INSOMNIA, AND DATA FROM OUR GROUP SUGGESTS THAT SUVOREXANT MIGHT BE ESPECIALLY EFFICACIOUS IN TREATING INSOMNIA IN PERSONS WITH OUD AND MAY ALSO CONFER COLLATERAL BENEFITS INCLUDING DECREASED OPIOID CRAVING AND SYMPTOMS OF WITHDRAWAL. MOREOVER, SUVOREXANT HAS AN EXCELLENT SAFETY PROFILE AND DID NOT RESULT IN INCREASED ADVERSE EVENTS OR MEASURES OF ABUSE POTENTIAL WHEN COMPARED TO PLACEBO IN OUR PILOT STUDY. THE PROPOSED STUDY IS AN FDA-REGULATORY-GRADE PHASE III MULTISITE RANDOMIZED-CONTROLLED TRIAL OF SUVOREXANT VERSUS PLACEBO IN PERSONS WITH INSOMNIA WHO ARE UTILIZING LONG-TERM MOUD TREATMENT. PARTICIPANTS WHO ARE PRESCRIBED BUPRENORPHINE OR METHADONE FOR OUD WILL BE SCREENED TO DETERMINE STUDY ELIGIBILITY. ELIGIBLE INDIVIDUALS WILL BE ENROLLED FOR AN 8-WEEK STUDY THAT INCLUDES THE FOLLOWING CONDITIONS: ONE NIGHT DOUBLE-DUMMY PLACEBO LEAD-IN PRIOR TO RANDOMIZATION; ~8 WEEKS OF SUVOREXANT OR PLACEBO WHERE THE DOSE MAY BE ESCALATED FROM 10 MG TO 20 MG AFTER 3 NIGHTS (CONSISTENT WITH CURRENT SUVOREXANT LABEL INSTRUCTIONS); AND TWO-NIGHTS DOUBLE-DUMMY PLACEBO LEAD-OUT TO EXAMINE DISCONTINUATION EFFECTS. IN LAB POLYSOMNOGRAPHY (PSG) WILL BE USED TO AT THE BEGINNING AND END OF THE TRIAL TO DETERMINE THE PRIMARY ENDPOINT OF CHANGE FROM BASELINE TOTAL SLEEP TIME. ADVERSE EVENTS AND OTHER INDICATORS OF PATIENT SAFETY WILL BE MONITORED THROUGHOUT THE STUDY. PARTICIPANTS WILL ALSO BE ASSESSED FOR OUD TREATMENT OUTCOMES INCLUDING REGULAR URINE TOXICOLOGY AND TRAJECTORIES OF MENTAL HEALTH DURING THE STUDY. SPECIFIC AIMS OF THE STUDY ARE TO (AIM 1) EVALUATE THE EFFICACY OF SUVOREXANT VERSUS PLACEBO IN TREAT INSOMNIA IN PERSONS TAKING BUPRENORPHINE OR METHADONE FOR OUD TREATMENT, (AIM1) EVALUATE THE SAFETY OF SUVOREXANT VERSUS PLACEBO IN PERSONS TAKING BUPRENORPHINE OR METHADONE FOR OUD TREATMENT, (AIM 3) SUBMIT A SUPPLEMENT APPLICATION OF EFFICACY TO THE FDA TO SUPPORT AN UPDATE TO THE LABEL OF SUVOREXANT, AND (EXPLORATORY AIM 4) DETERMINE WHETHER SUVOREXANT VERSUS PLACEBO IMPROVES OUD TREATMENT OUTCOMES. THE RESULTS OF THIS IMPORTANT STUDY WILL INFORM TREATMENT PROVIDERS ON WHETHER SUVOREXANT IS SAFE AND EFFECTIVE FOR INSOMNIA IN PERSONS WITH OUD, AND EXPLORATORY RESULTS WILL FURTHER OUR SCIENTIFIC UNDERSTANDING OF THE ROLE OF THE OREXIN SYSTEM IN OUD TREATMENT AND RECOVERY.