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Crossover study to evaluate the comparative bioavailability of two fixed dose combination tablet formulations of amlodipine and losartan in health volunteers

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GSK study ID

116797

See study documents

Clinicaltrials.gov ID

NCT01648231

EudraCT ID

Not applicable

EU CT Number

Not applicable

Trial status

Study complete

Overview

Eligibility

Locations

Study documents

Results summary

Plain language summaries

Additional information

Trial overview

Official 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

Trial description: 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.

Primary purpose:

Treatment

Trial design:

Crossover Assignment

Masking:

None (Open Label)

Allocation:

Randomized

Primary outcomes:

Plasma concentration of amlodipine and losartan: Peak plasma concentration (Cmax) and last measurable plasma concentration (Clast)

Timeframe: 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

Time to peak plasma concentration (Tmax) of amlodipine and losartan

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)

Elimination half-life (t½) of amlodipine and losartan

Secondary outcomes:

Number of healthy volunteers with adverse events

Plasma concentration of of carboxylic acid: Peak plasma concentration (Cmax)

Elimination half-life (t½) of carboxylic acid

Time to peak plasma concentration (Tmax) of carboxylic acid

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)

Interventions:

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

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

Drug: Fixed Dose Combination 2: 1 x 5mg amlodipine / 100mg losartan tablet administered in fasted state

Enrollment:

Primary completion date:

Not applicable

Observational study model:

Not applicable

Time perspective:

Not applicable

Clinical publications:

S Chung, J Bianco, J Bullman, A Stylianou, K Patterson. Evaluation of Bioequivalence of a Fixed Dose Combination of Amlodipine and Losartan: Results from Two Phase I Clinical Trials. British Pharmacological Society - Pharmacology 2014. 2014;12(3)

Medical condition

Hypertension

Product

amlodipine, amlodipine/losartan, losartan

Collaborators

Not applicable

Study date(s)

August 2012 to September 2012

Type

Interventional

Phase

Participation criteria

Sex

Female & Male

Age

18 - 65 years

Accepts healthy volunteers

Yes

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

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.

Inclusion and exclusion criteria

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.

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.

Trial location(s)

Location

Status

Location

GSK Investigational Site

Randwick, New South Wales, Australia, 2031

Status

Study Complete

Study documents

Clinical study report

Available language(s): English

Download document(s)

Scientific result summary

Available language(s): English

Download document(s)

Protocol

Available language(s): English

Download document(s)

If you wish to request for full study report, please contact - [email protected]

Results overview

Refer to study documents

Recruitment status

Study complete

Actual primary completion date

Not applicable

Actual study completion date

2012-25-09

Plain language summaries

Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

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