A Fixed Dose Combination Amlodipine + Enalapril Bioavailability Study
- Conditions
- Hypertension
- Interventions
- Registration Number
- NCT01822639
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 15
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Sequence 2 Enalapril Maleate 20 mg 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. Sequence 1 GSK2944404 FDC 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. Sequence 1 Amlodipine 5 mg 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. Sequence 1 Enalapril Maleate 20 mg 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. Sequence 2 GSK2944404 FDC 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. Sequence 2 Amlodipine 5 mg 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.
- Primary Outcome Measures
Name Time Method Relative oral bioavailability of GSK2944404 FDC to amlodipine and enalapril maleate tablets co-administered as assessed by composite of pharmacokinetic (PK) parameters. 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. 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.
- Secondary Outcome Measures
Name Time Method Composite of PK parameters for enalaprilat following administration of GSK2944404 and co-administration of amlodipine and enalapril maleate as data permit. 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. 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).
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 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. PK parameters include: tmax, Clast, percentage AUCex, and t1/2.
Vital signs measurements to assess safety and tolerability. Up to 35 days. Vital signs include blood pressure and pulse rate measurement. Orthostatic (sitting in upright position) as well as supine vitals will be measured.
Absolute values and change over time of Clinical laboratory parameters to assess safety and tolerability. Up to 35 days. Clinical laboratory parameters include: hematology, clinical chemistry, urinalysis and additional parameters.
Number of participants with adverse events (AEs) as a measure of safety and tolerability. Up to 35 days. AEs will be collected from the start of Study Treatment and until the follow-up contact visit.
Trial Locations
- Locations (1)
GSK Investigational Site
🇦🇺Randwick, New South Wales, Australia