Comparative assessment in healthy male volunteers under fasting conditions of the absorption and pharmacokinetics of 3 generic formulations of isotretinoin capsules against the innovator isotretinoin capsule in a pilot study

INTERVENTION: Single dose, crossover study design whereby each participant receives the test formulations of isotretinoin, 1 x 40 mg capsule (T1, T2 and T3) on one occasion each and the innovator formulation of isotretinoin, 1 x 40 mg capsule on one occasion. The intervention for this trial is the test formulations of isotretinoin. No water is allowed for 1 hour prior to dosing until 1 hour after dosing (except for the water consumed with each dose). Participants are required not to eat for 10 hours before receiving each dose and to fast for approximately 4 hours after each dose. Bathroom visits will be supervised to ensure no unauthorized 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 for 24 hours after dosing. Participants will be monitored for adverse events throughout the study. 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. Pre and post study laboratory tests will be completed to assess the health of the participants along with HIV, Hepatitis and drugs of abuse testing. Each dose 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 that the medication has been taken as directed. Each dose is separated by a one week washout period. CONDITION: Pilot study conducted in healthy volunteers comparing four formulations of isotretinoin with no health condition or problem studied. Although this study is being conducted in healthy volunteers who are not being treated for the condition to which the medicine is used, isotretinoin is a medicine that is used to treat severe forms of acne. PRIMARY OUTCOME: To evaluate the pharmacokinetics (as summarised by Cmax and AUC) of the three test formulations relative to that of the reference formulation. All plasma samples will be assayed for isotretinoin using one fully validated LC/MS/MS method. Validation will be conducted to comply with FDA guidelines. SECONDARY OUTCOME: Time to maximum peak concentration (Tmax) will be determined by plasma sample analysis. Tmax will be the time where the maximum concentration occurred in the sample points. INCLUSION CRITERIA: Healthy males Aged between 18 and 55 years Non‐smoker BMI greater than or equal to 19 and less than 30 inclusive Normal, healthy individuals as determined by medical history, physical examination, ECG, blood pressure and laboratory tests Drug free as determined by urine drug testing Able to comply with the study restrictions Able to provide written information consent