Bioavailability Study of Candesartan Cilexetil 16mg Tablet Under Fasting Conditions

NCT ID: NCT02006602

Last Updated: 2018-03-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-13
• Study Completion Date: 2014-01-22

Brief Summary

This will be an open-label, randomized, single dose, two-way crossover study. Each subject will participate in both treatment periods and will receive single oral doses of candesartan cilexetil (GW615775) and reference candesartan cilexetil (ATACAND™); the treatment periods will be separated by a washout period of at least 7 days and no greater than 14 days. This study aims to determine the relative bioavailability of a 16mg test formulation tablet of candesartan cilexetil (GW615775) compared to an 16mg reference tablet of candesartan cilexetil in healthy adult subjects. ATACAND is a registered trademark of the Astra/Zeneca group of companies.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1 reference then test

Subjects will be randomized and receive the following two treatments administered orally in a fasting state: A=Single dose of candesartan cilexetil (Reference treatment) 16mg; B= Single dose of candesartan cilexetil (Test formulation) 16mg. The two treatment periods will be separated by a washout period of at least 7 days and no more than 14 days.

Group Type: EXPERIMENTAL

Candesartan cilexetil (GW615775, Test formulation)

Intervention Type: DRUG

Test formulation candesartan cilexetil 16 mg will be supplied as round, biconvex white tablets with PX 16 embossed in one face and scored in the other face.

Candesartan cilexetil (Reference treatment)

Intervention Type: DRUG

Reference treatment of candesartan cilexetil 16 mg will be supplied as round, biconvex pink tablets, scored in one face and with embossment in both faces (016 embossment in the plain face and A CH in the scored face).

Arm 2 test then reference

Subjects will receive the following two treatments administered orally in a fasting state: A= Single dose of candesartan cilexetil (Test formulation) 16mg. B=Single dose of candesartan cilexetil (Reference treatment) 16mg. The two treatment periods will be separated by a washout period of at least 7 days and no more than 14 days.

Group Type: EXPERIMENTAL

Candesartan cilexetil (GW615775, Test formulation)

Intervention Type: DRUG

Test formulation candesartan cilexetil 16 mg will be supplied as round, biconvex white tablets with PX 16 embossed in one face and scored in the other face.

Candesartan cilexetil (Reference treatment)

Intervention Type: DRUG

Reference treatment of candesartan cilexetil 16 mg will be supplied as round, biconvex pink tablets, scored in one face and with embossment in both faces (016 embossment in the plain face and A CH in the scored face).

Interventions

Candesartan cilexetil (GW615775, Test formulation)

Test formulation candesartan cilexetil 16 mg will be supplied as round, biconvex white tablets with PX 16 embossed in one face and scored in the other face.

Intervention Type: DRUG

Candesartan cilexetil (Reference treatment)

Reference treatment of candesartan cilexetil 16 mg will be supplied as round, biconvex pink tablets, scored in one face and with embossment in both faces (016 embossment in the plain face and A CH in the scored face).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• Body weight >= 50kg and body mass index within the range 19 - 24.9 kilogram per square meter (kg/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 (FSH) > 40 milli-international units (MIU) per milliliter (mL) and estradiol <40 pigogram per mL (pg/mL) (<147 picomole per liter) is confirmatory. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in protocol 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 most forms 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 with negative pregnancy test as determined by serum and urine human chorionic gonadotropin (hCG) test at screening or prior to dosing and Agrees to use one of the contraception methods listed in Protocol 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 visitor 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 listed in Protocol. 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 transaminase, alkaline phosphatase and bilirubin <= 1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
• Based on single or averaged corrected QT interval (QTc) of triplicate electrocardiograms (ECGs) obtained over a brief recording period: QT duration corrected for heart rate by Fridericia's formula (QTcF) <450 milliseconds (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. One unit is equivalent to 8 gram of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• 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.
• Gastrointestinal disease or with gastrointestinal surgical history which can affect the absorption of the investigational drug.
• Any subject with a systolic blood pressure (BP) <95 millimeters of mercury (mmHg) or with a recent history of postural symptoms
• 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 immunodeficiency virus (HIV) antibody.
• Pregnant females as determined by positive serum hCG test at screening or prior to dosing.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 90 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: 90 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Hyderabad, , India

Countries

India

Study Documents

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

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Other Identifiers

201011

Identifier Type: -

Identifier Source: org_study_id