Comparative assessment of the absorption of a generic formulation of buprenorphine transdermal patch against the innovator buprenorphine transdermal patch conducted under fasting conditions and at steady state with the inclusion of a naltrexone block in healthy male and female volunteers

INTERVENTION: Multiple dose, crossover study design whereby each participant receives the test formulation of buprenorphine (1 x 20 mcg/hr patch) on three occasions with the patch being replaced every 7 days, and the innovator formulation of buprenorphine (1 x 20 mcg/hr patch) on three occasions with the patch being replaced every 7 days with the inclusion of a naltrexone block given 12 hours prior to patch application, at application and every 24 hours up until removal of the last patch in each study period. Each naltrexone dose will be 50 mg. Each buprenorphine dosing will be seperated by a four week washout period. The intervention for this trial is the test formulation of buprenorphine . Study Days 1 and 15 of each study period no water is allowed for 1 hour prior to dosing until 1 hour after dosing (except for the water consumed with the dose). Participants are required not to eat for 10 hours before receiving each dose on days 1 and 15 in each study period and to fast for approximately 4 hours after receiving each dose on days 1 and 15 of each study period. Bathroom visits will be supervised to ensure no unauthorised water or food intake and for personal safety. Participants will be confined at the Clinical Site for 12 hours prior to dosing to ensure compliance and will be monitored and for 24 hours after dosing. Standard meals will be consumed at the Clinical Site with no additional food intake allowed. Alcohol breath testing will be performed upon each participant reporting to the Clinical Site 12 hours prior to dosing. On study days 2‐14 and 16‐22 subjects will report to Zenith Technology for the provision of one blood sample. Pre and post study laboratory tests will be completed to assess the health of participants along with HIV, Hepatitis and drugs of abuse testing. Each buprenorphine patch will be applied to the upper arm with each consecutive patch applied to a different site. Investigators will examine every subject to ensure the patch has been applied correctly. Each dose of naltrexone will be taken orally with 240 ml of water at ambient temperature. Medication must be swallowed whole and a mouth check will be conducted to ensure the medication has been taken as directed. CONDITION: Buprenorphine is a partial opioid agonist indicated for the management of moderate to severe pain. PRIMARY OUTCOME: To compare the bioavailability of buprenorphine (as summarised by AUC0‐t(ss), Cmax(ss) and Cmin(ss)). All plasma samples will be assayed for buprenorphine using one fully validated LC/MS/MS method. Validation will be conducted to comply with EU and FDA guidelines. SECONDARY OUTCOME: All plasma samples will be assayed for buprenorphine to determine time to maximum peak concentration (Tmax) and the elimination half life (t1/2). Tmax will be the time where the maximum concentration occurred in the sample points. T1/2 = 0.693/Kel where kel is the terminal elimination rate constant. INCLUSION CRITERIA: Healthy male and non‐pregnant females Aged between 18 and 55 Non‐smoker BMI between 18.5 and 30 inclusive Normal, healthy individuals as determined by medical history, physical examination, ECG, blood pressure and laboratory tests Able to provide written informed consent