Hypertension
Conditions
Keywords
Hypertension, enalapril maleate, healthy volunteers, amlodipine, pharmacokinetics
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.
Interventions
Peach triangle shaped 20 mg enalapril maleate tablet for single dose oral co-administration with amlodipine in each period.
DRUGGSK2944404 FDC
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.
DRUGAmlodipine 5 mg
Emerald-shaped white 5 mg amlodipine table for single dose oral co-administration with enalapril maleate tablet in each period.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female aged between 18 and 65 years of age inclusive, at the time of signing the informed consent. * Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included only if the Investigator, in consultation with the GlaxoSmithKline (GSK) Medical Monitor if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body weight \>=50 kilograms (kg) and Body Mass Index within the range 19 to 32 kg/meter squared (m\^2) (inclusive). * A female subject is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy \[for this definition, documented refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records\]; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone \> 40 milli international unit (MlU)/ milliliter (mL) and estradiol \< 40 picogram/mL (\<147 picomoles/liter) is confirmatory\]. OR Child-bearing potential with negative pregnancy test as determined by serum human chorionic gonadotropin test at screening or prior to dosing. Agrees to use one of the contraception methods for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until the follow-up contact visit. OR has only same-sex partners, when this is her preferred and usual lifestyle. * Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods This criterion must be followed from the time of the first dose of study medication until the follow-up contact visit. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * Alanine aminotransferase, alkaline phosphatase and bilirubin \<=1.5 x upper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent). * Based on single or averaged QT duration corrected for heart rate (QTc) values of triplicate electrocardiograms (ECGs)obtained over a brief recording period: QTc by Fridericia's formula \<450 millisecond (msec).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
Australia
Outcome results
None listed