A Fixed Dose Combination Amlodipine + Enalapril Bioavailability Study

NCT01822639 | Completed Phase 1

• 1 other identifier: 116798
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension

Keywords

Hypertension; enalapril maleate; healthy volunteers; amlodipine; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (5)

• 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.

• 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.

• Number of participants with adverse events (AEs) as a measure of safety and tolerability.

  Up to 35 days.

• Vital signs measurements to assess safety and tolerability.

  Up to 35 days.

• Absolute values and change over time of Clinical laboratory parameters to assess safety and tolerability.

  Up to 35 days.

Study Arms (2)

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.

Drug: GSK2944404 FDC; Drug: Amlodipine 5 mg; Drug: Enalapril Maleate 20 mg

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.

Drug: GSK2944404 FDC; Drug: Amlodipine 5 mg; Drug: Enalapril Maleate 20 mg

Interventions

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.

Sequence 1; Sequence 2

Amlodipine 5 mg DRUG

Emerald-shaped white 5 mg amlodipine table for single dose oral co-administration with enalapril maleate tablet in each period.

Sequence 1; Sequence 2

Enalapril Maleate 20 mg DRUG

Peach triangle shaped 20 mg enalapril maleate tablet for single dose oral co-administration with amlodipine in each period.

Sequence 1; Sequence 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.

You may not qualify if:

• 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).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (With the exception of Gilbert's syndrome or asymptomatic gallstones).
• History of regular alcohol consumption within 6 months of the study defined as An average weekly intake of \>21 units for males or \>14 units for females. In Australia one unit (=standard drink) is equivalent to 10 grams of alcohol: 270 mL of full strength beer (4.8 percent), 375 mL of mid strength beer (3.5 percent), 470mL of light beer (2.7 percent), 250 mL pre-mix full strength spirit (5 percent), 100 mL of wine (13.5 percent) and 30 mL of spirit (40 percent).
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• A positive pre-study drug/alcohol screen.
• A positive test for human immuno virus antibody.
• Pregnant females as determined by positive serum hCG test at screening or at any other time points.
• Any subject with a systolic blood pressure \<95 millimeter of mercury (mmHg) or with a recent history of postural symptoms.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

Location

Related Links

• Results for study 116798 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Hypertension

Interventions

Amlodipine; Enalapril

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2013
• First Posted: April 2, 2013
• Study Start: April 3, 2013
• Primary Completion: May 24, 2013
• Study Completion: May 24, 2013
• Last Updated: June 5, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

AU (1)