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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment A (27.5 mg total maximum dose) | Experimental | 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) | Experimental | 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) | Experimental | 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) | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tab carvedilol 25 mg | Drug | Carvedilol 25 mg immediate release tablet |
|
| Measure | Description | Time Frame |
|---|---|---|
| The AUC for both the enriched and non-enriched R- and S-isomers of carvedilol | 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 | 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 Cmax for both the enriched and non-enriched R- and S-isomers of carvedilol | The pharmacokinetic parameters will include maximum drug concentration (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 |
| Measure | Description | Time Frame |
|---|---|---|
| The Tmax for both the enriched and non-enriched R- and S-isomers of carvedilol (as data permit) | 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 | 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 |
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Inclusion criteria
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Cambridge | CB2 2GG | United Kingdom |
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| Label | URL |
|---|---|
| Results for study 117058 can be found on the GSK Clinical Study Register. | View source |
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| Tab carvedilol 6.25 mg | Drug | Carvedilol 6.25 mg immediate release tablet |
|
| Powder carvedilol up to 2.5 mg | Drug | Carvedilol up to 2.5 mg isotopically enriched drug substance powder |
|
| The T1/2 for both the enriched and non-enriched R- and S-isomers of carvedilol (as data permit) | 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 | 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 |
| ID | Term |
|---|---|
| D000077261 | Carvedilol |
| ID | Term |
|---|---|
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D002227 | Carbazoles |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D006575 | Heterocyclic Compounds, 3-Ring |
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