Randomised Comparison of a Novel Buprenorphine Oral Lyophilisate versus Existing Buprenorphine Sublingual Tablets in Opioid-Dependent Patients: A First-in-Patient Phase II Randomised Open Label Safety Study

Abstract

Aims: To test the safety of new buprenorphine oral lyophilisate wafer (“bup-lyo”) versus standard sub-lingual buprenorphine (“bup-SL”). Design: Randomised (2:1) open-label study; opioid-dependent subjects; subsequent partial cross-over. Settings: Specialised clinical trials facility and addictions treatment facility. Participants: Opioid-dependent subjects (n = 36) commencing buprenorphine maintenance (personalised dose-titration) including patients co-using alcohol, cocaine and benzodiazepines (below thresholds). Measurements: Respiratory function (respiratory rate, pulse-oximetry); medication hold and dose adequacy; opiate withdrawal signs and symptoms; tablet disintegration times; treatment retention. Pharmacokinetics (PK) for plasma buprenorphine and norbuprenorphine (n = 11). Findings: Oral lyophilised buprenorphine (“bup-lyo”) completely dissolved within 2 min for 58 vs. 5% for “bup-SL.” Dose titration resulted in similar maintenance dosing (10.8 vs. 9.6 mg). There were no significant between-group differences in opiate-withdrawal phenomena, craving, adequacy of “hold,” respiratory function. No serious adverse events (AEs), nor “severe” AEs, although more AEs and Treatment-Emergent AEs with “bup-lyo” (mostly “mild”). PK found greater bioavailability of buprenorphine with “bup-lyo” (but not norbuprenorphine). Conclusions: Orally disintegrating buprenorphine oral lyophilisate wafer disintegrated rapidly. No increased respiratory depression was found and clinically no difference between medications was observed. PK found substantially increased bioavailability of buprenorphine (but not of nor-buprenorphine) with “bup-lyo” relative to “bup-SL.” In supervised dosing contexts, rapidly disintegrating formulations may enable wider buprenorphine prescribing.

Rapid titration of opiate doses via patient-controlled intravenous analgesia for patients with severe cancer pain

“…Based on this unique feature of opioid drugs, first dose titration is emphasized in the initial clinical opioid or opiate dose adjustments to ensure safe and effective individualized drug use. 4 Due to the slow onset of oral morphine, patients need to adjust the dose several times to obtain accurate opioid demand. It usually takes 2-3 days to complete one titration, or even longer.…”

Perspectives on the Pharmacological Treatment of Heroin Addiction

“…A very recent development is a buprenorphine oral lyophilisate wafer which has been shown to be as effective as the sublingual tablet but which dissolves much more rapidly. 55…”

“…A very recent development is a buprenorphine oral lyophilisate wafer which has been shown to be as effective as the sublingual tablet but which dissolves much more rapidly. 55 It can be concluded that buprenorphine may not be the preferred treatment for many patients, especially those with complex needs. However, it is a valuable option for patients who have a relatively stable life but whose drug use has temporarily got out of control.…”

Depot buprenorphine injections for opioid use disorder: Patient information needs and preferences

“…Historically, these medications have almost always been taken daily, in liquid/linctus or tablet//film form, with injectables occasionally provided to patients who repeatedly fail to benefit from oral formulations . Opioid agonist treatment is closely monitored by regulatory authorities and clinicians, and medication consumption is often physically supervised in a drug treatment or community pharmacy setting .…”

“…In addition, patients have complained that the process of frequent dosing is stigmatising, restricts their freedom, and undermines their quality of life by making it difficult to work, take a holiday, and participate in other everyday activities . Unsurprisingly, therefore, poor/non‐adherence and treatment dropout are common in MAT .…”