buprenorphine--naloxone-drug-combination and Respiratory-Insufficiency

There is an unmet need for therapeutics with greater efficacy and tolerability for the treatment of opioid use disorder (OUD). ASP8062 is a novel compound with positive allosteric modulator activity on the γ-aminobutyric acid type B receptor under development for use with standard-of-care treatment for patients with OUD.. To investigate the safety, tolerability, interaction potential, and pharmacokinetics (PK) of ASP8062 in combination with buprenorphine/naloxone (B/N; Suboxone. In this phase 1, randomized, double-masked, placebo-controlled study, patients with OUD began B/N (titrated to 16/4 mg/day) treatment upon enrollment (induction, Days 1-4; maintenance, Days 5-18; downward titration, Days 19-26; and discharge, Day 27). On Day 12, patients received a single dose of ASP8062 60 mg or placebo with B/N and underwent safety and PK assessments. Primary endpoints included frequency and severity of treatment-emergent adverse events (TEAEs), clinical laboratory tests, respiratory depression, and suicidal ideation. Secondary endpoints investigated the impact of ASP8062 on B/N PK.. In this phase 1 study, ASP8062 was safe, well tolerated, and did not enhance respiratory suppression induced by buprenorphine.. Clinicaltrials.gov identifier: NCT04447287.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Double-Blind Method; Humans; Narcotic Antagonists; Opioid-Related Disorders; Respiratory Insufficiency

Exploratory buprenorphine ingestions in young children have been associated with clinically significant toxicity. However, detailed data on the clinical presentation and management of these patients are lacking. In an attempt to obtain more comprehensive data, we sought to examine a single center cohort of patients with report of buprenorphine exposure and provide descriptive analysis of rates of respiratory depression, time to respiratory depression, interventions, disposition, and outcomes.. We performed a retrospective cohort study at a single pediatric tertiary care center of children between the age of 6 months and 7 years of age hospitalized between 1 January 2006 and 1 September 2014 with report of buprenorphine or buprenorphine/naloxone exposure. Patients with possible exposure to more than one agent were excluded. We extracted clinical findings, including time to respiratory depression, interventions, and disposition from the medical record.. Pediatric patients exposed to buprenorphine are likely to exhibit signs and symptoms of opioid toxicity, including respiratory depression, altered mental status and miosis. Although the majority of patients developed signs of clinical toxicity within 8 h of reported exposure, the optimum duration of monitoring remains unclear.

Topics: Analgesics, Opioid; Antidotes; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Charcoal; Child; Child, Preschool; Cohort Studies; Female; Hospitalization; Humans; Infant; Length of Stay; Male; Narcotic Antagonists; Oximetry; Oxygen; Respiratory Insufficiency; Retrospective Studies; Time Factors