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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01822639




Registration number
NCT01822639
Ethics application status
Date submitted
28/03/2013
Date registered
2/04/2013
Date last updated
5/06/2017

Titles & IDs
Public title
A Fixed Dose Combination Amlodipine + Enalapril Bioavailability Study
Scientific title
An Open-Label, Randomized, Single Dose, Two-Way Crossover Pilot Study to Evaluate the Relative Bioavailability of One Amlodipine 5 mg Tablet and One Enalapril Maleate 20mg Tablet to a Fixed Dose Combination Tablet Formulation of Amlodipine (5 mg) and Enalapril Maleate (20 mg), in Healthy Adult Male and Female Subjects Under Fasting Conditions
Secondary ID [1] 0 0
116798
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypertension 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK2944404 FDC
Treatment: Drugs - Amlodipine 5 mg
Treatment: Drugs - Enalapril Maleate 20 mg

Experimental: Sequence 1 - 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.

Experimental: Sequence 2 - 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.


Treatment: Drugs: GSK2944404 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.

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

Treatment: Drugs: Enalapril Maleate 20 mg
Peach triangle shaped 20 mg enalapril maleate tablet for single dose oral co-administration with amlodipine in each period.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Relative oral bioavailability of GSK2944404 FDC to amlodipine and enalapril maleate tablets co-administered as assessed by composite of pharmacokinetic (PK) parameters.
Timepoint [1] 0 0
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 outcome [1] 0 0
Composite of PK parameters for enalaprilat following administration of GSK2944404 and co-administration of amlodipine and enalapril maleate as data permit.
Timepoint [1] 0 0
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.
Secondary outcome [2] 0 0
Composite of PK parameters for amlodipine and enalapril maleate following administration of GSK2944404 and co-administration of amlodipine and enalapril maleate as data permit.
Timepoint [2] 0 0
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 outcome [3] 0 0
Number of participants with adverse events (AEs) as a measure of safety and tolerability.
Timepoint [3] 0 0
Up to 35 days.
Secondary outcome [4] 0 0
Vital signs measurements to assess safety and tolerability.
Timepoint [4] 0 0
Up to 35 days.
Secondary outcome [5] 0 0
Absolute values and change over time of Clinical laboratory parameters to assess safety and tolerability.
Timepoint [5] 0 0
Up to 35 days.

Eligibility
Key inclusion criteria
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).
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion Criteria Based Upon Medical Histories

- 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.

Exclusion Criteria Based Upon Diagnostic Assessments

- 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.

- Orthostatic event at screening, defined as a symptomatic event (i.e. dizziness or any
pre syncope or syncope) and a reduction in systolic blood pressure of 20mmHg or more
and/or a reduction in diastolic blood pressure of 10 mmHg or more for standing versus
supine measurement.

Other Exclusion Criteria

- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period.

- Lactating females.

- The subject has participated in a clinical trial and has received an investigational
product within the following time period prior to the first dosing day in the current
study: 30 days, 5 half-lives or twice the duration of the biological effect of the
investigational product (whichever is longer).

- Exposure to more than four new chemical entities within 12 months prior to the first
dosing day.

- Unable to refrain from the use of prescription or non-prescription drugs, including
vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or
14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is
longer) prior to the first dose of study medication, unless in the opinion of the
Investigator and GSK Medical Monitor the medication will not interfere with the study
procedures or compromise subject safety.

- Subject is mentally or legally incapacitated.

- Positive carbon monoxide on admission to the Unit.

- Unable to refrain from consumption of red wine, seville oranges, grapefruit or
grapefruit juice (and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit
juices) from 7 days prior to the first dose of study medication.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/04/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/05/2013
Sample size
Target
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01822639
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries