A Study in Healthy Volunteers to Evaluate the Application of Stable Isotope Approach to Reduce Number of Subjects Needed for PK Studies

Phase 1

Completed

• Conditions: Metabolic, Cardiovascular
• Interventions: Drug: Tab carvedilol 25 mg; Drug: Powder carvedilol up to 2.5 mg; Drug: Tab carvedilol 6.25 mg

• Registration Number: NCT01793870
• Lead Sponsor: GlaxoSmithKline

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2013-01-15
• Study First Submitted: 2013-02-14
• Study First Submitted QC: 2013-02-14
• Study First Posted: 2013-02-18
• Primary Completion: 2013-06-17
• Study Completion: 2013-06-17
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-09
• Last Update Posted: 2017-06-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment A (27.5 mg total maximum dose)	Tab carvedilol 25 mg	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.
Treatment A (27.5 mg total maximum dose)	Powder carvedilol up to 2.5 mg	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.
Treatment B (27.5 mg total maximum dose)	Tab carvedilol 25 mg	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.
Treatment B (27.5 mg total maximum dose)	Powder carvedilol up to 2.5 mg	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.
Treatment C (33.75 mg total maximum dose)	Tab carvedilol 25 mg	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.
Treatment C (33.75 mg total maximum dose)	Tab carvedilol 6.25 mg	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.
Treatment C (33.75 mg total maximum dose)	Powder carvedilol up to 2.5 mg	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.
Treatment D (27.5 mg total maximum dose)	Tab carvedilol 25 mg	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.
Treatment D (27.5 mg total maximum dose)	Powder carvedilol up to 2.5 mg	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.

Primary Outcome Measures

Name	Time	Method
The AUC for both the enriched and non-enriched R- and S-isomers of carvedilol	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	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 Outcome Measures

Name	Time	Method
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 pharmacokinetic parameter will include the time when maximum drug concentration is reached (Tmax) for both the enriched and non-enriched R- and S-isomers of carvedilol
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	The pharmacokinetic parameter will include the half life of the drug (T1/2) for both the enriched and non-enriched R- and S-isomers of carvedilol

Trial Locations

Locations (1)

GSK Investigational Site; 🇬🇧 Cambridge, United Kingdom