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The study is designed to estimate the bioavailability of amlodipine and enalapril maleate fixed dose combination (FDC) relative to co-administration of amlodipine and enalapril maleate tablets. The rational for this study is to provide a more convenient dosing regimen for patients. This is an open-label, randomized, single dose, two-way crossover study, in which 16 healthy adult male and female subjects will be enrolled and dosed under fasting conditions. Each subject will participate in two treatment periods of 7 days each. There will be at least 14 days of wash out period between the two dosing periods and a follow-up period of up to 21 days after treatment period 2. The total duration of study will be approximately 35 days from the start of the first treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence 1 | Experimental | Subjects in this arm will receive Treatment A in period 1 and Treatment B in period 2. Treatment A is co-administration of 5mg amlodipine tablet and 20 mg enalapril maleate tablet. Treatment B (GSK2944404) is fixed dose combination tablet of 5 mg amlodipine and 20 mg enalapril. |
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| Sequence 2 | Experimental | Subjects in this arm will receive Treatment B in period 1 and Treatment A in period 2. Treatment A is co-administration of 5mg amlodipine tablet and 20 mg enalapril maleate tablet. Treatment B (GSK2944404) is fixed dose combination tablet of 5 mg amlodipine and 20 mg enalapril. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2944404 FDC | Drug | Uncoated, round, yellow white bilayer fixed dose combination tablet containing 5 mg amlodipine and 20 mg enalapril for single dose oral administration in each period. |
| Measure | Description | Time Frame |
|---|---|---|
| Relative oral bioavailability of GSK2944404 FDC to amlodipine and enalapril maleate tablets co-administered as assessed by composite of pharmacokinetic (PK) parameters. | PK parameters include: maximum observed concentration (Cmax) of amlodipine and enalapril in all treatments, area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC[0-t]), and area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC [0-infinity]. Bioavailability is defined as the amount of drug available at the site of action after administration. | PK samples will be collected at Pre-dose, 0.25, 0.5, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 36, 48, 72, 96, 120, and 144 hours post dose at each dosing session. |
| Measure | Description | Time Frame |
|---|---|---|
| Composite of PK parameters for enalaprilat following administration of GSK2944404 and co-administration of amlodipine and enalapril maleate as data permit. | PK parameters include: AUC (0-infinity), AUC (0-t), Cmax, time of occurrence of Cmax (tmax), percentage of AUC (0-infinity) obtained by extrapolation (percentage AUCex), last observed quantifiable concentration (Clast), and terminal phase half-life (t1/2). |
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Inclusion Criteria
Exclusion Criteria Based Upon Medical Histories
Exclusion Criteria Based Upon Diagnostic Assessments
Other Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Randwick | New South Wales | 2031 | Australia |
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| Label | URL |
|---|---|
| Results for study 116798 can be found on the GSK Clinical Study Register. | View source |
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 116798 | Dataset Specification | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D017311 | Amlodipine |
| D004656 | Enalapril |
| ID | Term |
|---|---|
| D004095 | Dihydropyridines |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Amlodipine 5 mg | Drug | Emerald-shaped white 5 mg amlodipine table for single dose oral co-administration with enalapril maleate tablet in each period. |
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| Enalapril Maleate 20 mg | Drug | Peach triangle shaped 20 mg enalapril maleate tablet for single dose oral co-administration with amlodipine in each period. |
|
| PK samples will be collected at Pre-dose, 0.25, 0.5, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose at each dosing session. |
| Composite of PK parameters for amlodipine and enalapril maleate following administration of GSK2944404 and co-administration of amlodipine and enalapril maleate as data permit. | PK parameters include: tmax, Clast, percentage AUCex, and t1/2. | PK samples will be collected at Pre-dose, 0.25, 0.5, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 36, 48, 72, 96, 120, and 144 hours post dose at each dosing session. |
| Number of participants with adverse events (AEs) as a measure of safety and tolerability. | AEs will be collected from the start of Study Treatment and until the follow-up contact visit. | Up to 35 days. |
| Vital signs measurements to assess safety and tolerability. | Vital signs include blood pressure and pulse rate measurement. Orthostatic (sitting in upright position) as well as supine vitals will be measured. | Up to 35 days. |
| Absolute values and change over time of Clinical laboratory parameters to assess safety and tolerability. | Clinical laboratory parameters include: hematology, clinical chemistry, urinalysis and additional parameters. | Up to 35 days. |
For additional information about this study please refer to the GSK Clinical Study Register |
| 116798 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116798 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116798 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116798 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116798 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116798 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| D004151 |
| Dipeptides |
| D009842 | Oligopeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |