A Four Way Crossover Study in Healthy Volunteers to Evaluate the Application of Stable Isotope Approach to Reduce Number of Subjects Needed for PK Studies
Overview
- Phase
- Phase 1
- Intervention
- Tab carvedilol 25 mg
- Conditions
- Metabolic, Cardiovascular
- Sponsor
- GlaxoSmithKline
- Enrollment
- 17
- Locations
- 1
- Primary Endpoint
- The AUC for both the enriched and non-enriched R- and S-isomers of carvedilol
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This will be a randomized, open-label, single dose, 4-period, period balanced, crossover study. There will be at least 5 days between dosing in each session. The study consists of Screening period (30 days prior to Day 1), Treatment period consisting of 4 dosing periods (Day 1 is the dosing day and Day 2) and Follow-up period (7-14 days post-last dose).
The detailed treatment regimen will be A and B (27.5 mg total maximum dose): Single oral dose of carvedilol 25 mg immediate release tablet and up to 2.5 mg of enriched carvedilol powder under fasted conditions; C (33.75 mg total maximum dose): Single oral dose of carvedilol 31.25 mg as 25 mg immediate release tablet, a 6.25 mg immediate release tablet and up to 2.5 mg of enriched carvedilol powder under fasted conditions; D (27.5 mg total maximum dose): Single oral dose of carvedilol 25 mg immediate release tablet and up to 2.5 mg of enriched carvedilol powder under fed conditions. Approximately 15 subjects will be randomized to receive one of four treatment sequences (ADBC, BACD, CBDA, or DCAB).
The pharmacokinetic sampling and safety data will be collected in the Treatment period (Day 1 and 2).
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment A (27.5 mg total maximum dose)
Single oral dose of carvedilol (25 milligram \[mg\]) as a 1 x 25 mg immediate release tablet and up to 2.5 mg of enriched carvedilol drug substance under fasted conditions.
Intervention: Tab carvedilol 25 mg
Treatment A (27.5 mg total maximum dose)
Single oral dose of carvedilol (25 milligram \[mg\]) as a 1 x 25 mg immediate release tablet and up to 2.5 mg of enriched carvedilol drug substance under fasted conditions.
Intervention: Powder carvedilol up to 2.5 mg
Treatment B (27.5 mg total maximum dose)
Single oral dose of carvedilol (25 mg) as a 1 x 25 mg immediate release tablet and up to 2.5 mg of enriched carvedilol drug substance under fasted conditions.
Intervention: Tab carvedilol 25 mg
Treatment B (27.5 mg total maximum dose)
Single oral dose of carvedilol (25 mg) as a 1 x 25 mg immediate release tablet and up to 2.5 mg of enriched carvedilol drug substance under fasted conditions.
Intervention: Powder carvedilol up to 2.5 mg
Treatment C (33.75 mg total maximum dose)
Single oral dose of carvedilol (31.25 mg) as a 1 x 25 mg immediate release tablet, a 1 x 6.25 mg immediate release tablet and up to 2.5 mg of enriched carvedilol drug substance under fasted conditions.
Intervention: Tab carvedilol 25 mg
Treatment C (33.75 mg total maximum dose)
Single oral dose of carvedilol (31.25 mg) as a 1 x 25 mg immediate release tablet, a 1 x 6.25 mg immediate release tablet and up to 2.5 mg of enriched carvedilol drug substance under fasted conditions.
Intervention: Tab carvedilol 6.25 mg
Treatment C (33.75 mg total maximum dose)
Single oral dose of carvedilol (31.25 mg) as a 1 x 25 mg immediate release tablet, a 1 x 6.25 mg immediate release tablet and up to 2.5 mg of enriched carvedilol drug substance under fasted conditions.
Intervention: Powder carvedilol up to 2.5 mg
Treatment D (27.5 mg total maximum dose)
Single oral dose of carvedilol (25 mg) as a 1 x 25 mg x immediate release tablet and up to 2.5 mg of enriched carvedilol drug substance under fed conditions.
Intervention: Tab carvedilol 25 mg
Treatment D (27.5 mg total maximum dose)
Single oral dose of carvedilol (25 mg) as a 1 x 25 mg x immediate release tablet and up to 2.5 mg of enriched carvedilol drug substance under fed conditions.
Intervention: Powder carvedilol up to 2.5 mg
Outcomes
Primary Outcomes
The AUC for both the enriched and non-enriched R- and S-isomers of carvedilol
Time Frame: Day 1:pre-dose, 15 minutes (mins), 30 mins, 45 mins, 1 hour (h), 2 h, 3 h, 4 h, 6 h, 8 h and 12 h post-dose; Day 2: at 24 h and 36 h post dose
The pharmacokinetic parameters will include area under the time concentration curve (AUC) for both the enriched and non-enriched R- and S-isomers of carvedilol
The Cmax for both the enriched and non-enriched R- and S-isomers of carvedilol
Time Frame: Day 1:pre-dose, 15 minutes (mins), 30 mins, 45 mins, 1 hour (h), 2 h, 3 h, 4 h, 6 h, 8 h and 12 h post-dose; Day 2: at 24 h and 36 h post dose
The pharmacokinetic parameters will include maximum drug concentration (Cmax) for both the enriched and non-enriched R- and S-isomers of carvedilol
Secondary Outcomes
- The Tmax for both the enriched and non-enriched R- and S-isomers of carvedilol (as data permit)(Day 1:pre-dose, 15 minutes (mins), 30 mins, 45 mins, 1 hour (h), 2 h, 3 h, 4 h, 6 h, 8 h and 12 h post-dose; Day 2: at 24 h and 36 h post dose)
- The T1/2 for both the enriched and non-enriched R- and S-isomers of carvedilol (as data permit)(Day 1:pre-dose, 15 minutes (mins), 30 mins, 45 mins, 1 hour (h), 2 h, 3 h, 4 h, 6 h, 8 h and 12 h post-dose; Day 2: at 24 h and 36 h post dose)