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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/NCT01648231




Registration number
NCT01648231
Ethics application status
Date submitted
12/07/2012
Date registered
24/07/2012
Date last updated
26/07/2017

Titles & IDs
Public title
Crossover Study to Evaluate the Comparative Bioavailability of Two Fixed Dose Combination Tablet Formulations of Amlodipine and Losartan in Health Volunteers
Scientific title
An Open-label, Randomized, Single Dose, Three-way Crossover Study to Determine the Comparative Bioavailability of Two Fixed Dose Combination Tablet Formulations of Amlodipine (5mg) and Losartan (100mg) in Healthy Adult Male and Female Subjects Under Fasting Conditions
Secondary ID [1] 0 0
116797
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 - Reference Treatment: 1 x 5mg amlodipine tablet and 1 x 100mg losartan tablet administered in fasted state
Treatment: Drugs - Fixed Dose Combination 1: 1 x 5mg amlodipine / 100mg losartan tablet administered in fasted state
Treatment: Drugs - Fixed Dose Combination 2: 1 x 5mg amlodipine / 100mg losartan tablet administered in fasted state

Other: Treatment Period 1 - 1 x 5mg amlodipine tablet and 1 x 100mg losartan tablet administered in fasted state

Other: Treatment Period 2 - 1 x 5mg amlodipine / 100mg losartan tablet administered in fasted state

Other: Treatment Period 3 - 1 x 5mg amlodipine / 100mg losartan tablet administered in fasted state


Treatment: Drugs: Reference Treatment: 1 x 5mg amlodipine tablet and 1 x 100mg losartan tablet administered in fasted state
1 x 5mg amlodipine tablet and 1 x 100mg losartan tablet administered in fasted state

Treatment: Drugs: Fixed Dose Combination 1: 1 x 5mg amlodipine / 100mg losartan tablet administered in fasted state
1 x 5mg amlodipine / 100mg losartan tablet administered in fasted state

Treatment: Drugs: Fixed Dose Combination 2: 1 x 5mg amlodipine / 100mg losartan tablet administered in fasted state
1 x 5mg amlodipine / 100mg losartan tablet administered in fasted state
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Plasma concentration of amlodipine and losartan: Peak plasma concentration (Cmax) and last measurable plasma concentration (Clast)
Timepoint [1] 0 0
Participants will be followed and monitored for the duration of their hospital stay (24 hours per treatment period). The longest duration of participation in the study will be approximately 14 weeks
Primary outcome [2] 0 0
Time to peak plasma concentration (Tmax) of amlodipine and losartan
Timepoint [2] 0 0
Participants will be followed and monitored for the duration of their hospital stay (24 hours per treatment period). The longest duration of participation in the study will be approximately 14 weeks
Primary outcome [3] 0 0
Area under the plasma concentration-time curve (AUC) of amlodipine and losartan: from time zero to time t (AUCt), from time zero to infinity (AUCinf) and time t to infinity as a percentage of total AUC (%AUCex)
Timepoint [3] 0 0
Participants will be followed and monitored for the duration of their hospital stay (24 hours per treatment period). The longest duration of participation in the study will be approximately 14 weeks
Primary outcome [4] 0 0
Elimination half-life (t½) of amlodipine and losartan
Timepoint [4] 0 0
Participants will be followed and monitored for the duration of their hospital stay (24 hours per treatment period). The longest duration of participation in the study will be approximately 14 weeks
Secondary outcome [1] 0 0
Number of healthy volunteers with adverse events
Timepoint [1] 0 0
Participants will be followed and monitored for the duration of their hospital stay (24 hours per treatment period). The longest duration of participation in the study will be approximately 14 weeks
Secondary outcome [2] 0 0
Plasma concentration of of carboxylic acid: Peak plasma concentration (Cmax)
Timepoint [2] 0 0
Participants will be followed and monitored for the duration of their hospital stay (24 hours per treatment period). The longest duration of participation in the study will be approximately 14 weeks
Secondary outcome [3] 0 0
Elimination half-life (t½) of carboxylic acid
Timepoint [3] 0 0
Participants will be followed and monitored for the duration of their hospital stay (24 hours per treatment period). The longest duration of participation in the study will be approximately 14 weeks
Secondary outcome [4] 0 0
Time to peak plasma concentration (Tmax) of carboxylic acid
Timepoint [4] 0 0
Participants will be followed and monitored for the duration of their hospital stay (24 hours per treatment period). The longest duration of participation in the study will be approximately 14 weeks
Secondary outcome [5] 0 0
Area under the plasma concentration-time curve (AUC) of carboxylic acid: from time zero to time t (AUCt), from time zero to infinity (AUCinf) and time t to infinity as a percentage of total AUC (%AUCex)
Timepoint [5] 0 0
Participants will be followed and monitored for the duration of their hospital stay (24 hours per treatment period). The longest duration of participation in the study will be approximately 14 weeks

Eligibility
Key inclusion criteria
- Male or female between 18 and 65 years of age inclusive, at the time of signing the
informed consent.

- Alanine transaminase (ALT), 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%)

- Normal electrocardiogram (ECG) morphology and measurements. In particular QTc <450
msec or QT < 480 msec in subjects with Bundle Branch Block based on an average from
three ECGs obtained over a brief recording period.

- 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 parameters
outside the reference range for the population being studied may be included only if
the Investigator feels that the finding is unlikely to introduce additional risk
factors and will not interfere with the study procedures..

- 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; or postmenopausal defined as 12 months of spontaneous amenorrhea
(in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH)
> 40 MlU/ml and estradiol < 40 pg/ml (<147 pmol/L) is confirmatory. Females on hormone
replacement therapy (HRT) and whose menopausal status is in doubt will be required to use a
protocol approved contraception method if they wish to continue their HRT during the study.
Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior
to study enrollment. For mostforms of HRT, at least 2-4 weeks will elapse between the
cessation of therapy and the blood draw; this interval depends on the type and dosage of
HRT. Following confirmation of their post-menopausal status, they can resume use of HRT
during the study without use of a contraceptive method.

Child-bearing potential and agrees to use one of the protocol approved 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 14 days post-last dose
of amlodipine/losartan.

- Body weight = 50 kg and a body mass index (BMI) within the range 19 - 32 kg/m2
(inclusive).

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening.

- Any subject with a systolic blood pressure (BP) <95mmHg or with a recent history of
postural symptoms.

- Current or chronic history of liver disease, or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome or asymptomatic gallstones).

- A positive pre-study drug/alcohol screen.

- A positive test for HIV antibody.

- 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. One unit is
equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (100 ml) of wine or 1
(25 ml) measure of spirits.

- 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.

- 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.

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

- Pregnant females as determined by positive urine human chorionic gonadotrophin (hCG)
test at Day -1 or serum hCG at all other timepoints.

- Lactating females.

- Unwillingness or inability to follow the procedures outlined in the protocol.

- Subject is mentally or legally incapacitated.

- History of sensitivity to heparin or heparin-induced thrombocytopenia.

- Subjects who have asthma or a history of asthma

- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or
nicotine-containing products within 6 months prior to screening.

- Positive carbon monoxide (CO) 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
6/08/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
25/09/2012
Sample size
Target
Accrual to date
Final
23
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 purpose of this study is to evaluate the comparative bioavailability of two fixed dose
combination tablet formulations of amlodipine and losartan in healthy volunteers. Subjects
will receive each of the following three treatments administered in a randomized three-way
crossover design: a reference treatment consisting of a 5mg amlodipine tablet and 100mg
losartan tablet; a fixed dose combination tablet consisting of 5mg amlodipine and 100mg
losartan; and another fixed dose combination tablet consisting of 5mg amlodipine and 100mg
losartan; all three treatments will be administered once orally and in a fasted state. Serial
blood samples will be obtained at pre-defined timepoints for pharmacokinetic analysis of
amlodipine, losartan and carboxylic acid (this is the primary active losartan metabolite).
Safety assessments will include measurements of orthostatic vital signs, electrocardiograms
(ECG), collection of adverse events (AE) and clinical laboratory tests.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01648231
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01648231