A Relative Bioavailability Study of a Fixed Dose Combination (FDC) Tablets of GSK587323

NCT02094924 | Completed Phase 1

• 1 other identifier: 200957
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This study is required to confirm the suitability of a candidate FDC of 16mg candesartan cilexetil/12.5mg HCTZ (GSK587323) formulation for further development and provide data to allow the design of a future pivotal bioequivalence study. This study aims to determine the relative bioavailability of a FDC tablet formulation of 16mg candesartan cilexetil/12.5mg HCTZ relative to the reference product of same fixed dose combination (16mg candesartan cilexetil/12.5mg HCTZ) in healthy adult humans. This will be an open-label, randomised, single dose, two-way crossover study. Each subject will participate in two treatment periods and will be randomized to one of two sequences and administered one of the two treatments, A or B, as per the randomization schedule. The two treatment periods will be separated by a washout period of 7 to 14 days to ensure the candesartan and HCTZ have been effectively eliminated from the subject between dosing occasions. The study will enroll 16 healthy subjects to ensure that 14 subjects complete the study as planned.

Conditions

Hypertension

Keywords

Candesartan cilexetil; Hypertension; Hydrochlorothiazide; Healthy adult human subjects; Bioequivalence

Outcome Measures

Primary Outcomes (1)

• Composite of PK parameters for candesartan and HCTZ to assess relative bioavailability.

  PK parameters include: maximum observed plasma concentration (Cmax), area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC \[0-infinite\]) and area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC \[0-t\]). Twenty four blood samples (1x 5mililiter (mL)) will be collected at the specified time points for PK analysis of candesartan and HCTZ.

  Pre dose, 0.33, 0.67, 1, 1.33, 1.67, 2.0, 2.33, 2.67, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 16, 24, 36, and 48hours post dose in each treatment period.

Secondary Outcomes (4)

• PK profile of candesartan and HCTZ.

  Pre dose, 0.33, 0.67, 1, 1.33, 1.67, 2.0, 2.33, 2.67, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 16, 24, 36, and 48hours post dose in each treatment period.

• Vital sign assessment as a measure of safety and tolerability.

  Up to 39 days

• Review of adverse events (AEs) as a measure of safety and tolerability.

  Up to 39 days

• Clinical laboratory data assessment as measure of safety and tolerability.

  Up to 39 days

Study Arms (2)

Sequence 1

EXPERIMENTAL

Participants in this arm will receive treatment A in period 1 and treatment B in period 2. Subjects will receive a single reference FDC tablet of 16mg candesartan cilexetil/12.5mg HCTZ as Treatment A administered orally with 240mL of water and a single 16mg candesartan cilexetil/12.5mg HCTZ FDC tablet (GSK587323) as Treatment B.

Drug: GSK587323; Drug: FDC of candesartan cilexetil 16 mg and HCTZ 12.5mg

Sequence 2

EXPERIMENTAL

Participants in this arm will receive treatment B in period 1 and treatment A in period 2. Subjects will receive a single reference FDC tablet of 16mg candesartan cilexetil/12.5mg HCTZ as Treatment A administered orally with 240mL of water and a single 16mg candesartan cilexetil/12.5mg HCTZ FDC tablet (GSK587323) as Treatment B.

Drug: GSK587323; Drug: FDC of candesartan cilexetil 16 mg and HCTZ 12.5mg

Interventions

GSK587323 DRUG

Single dose of FDC tablet formulation to be taken orally.

Sequence 1; Sequence 2

FDC of candesartan cilexetil 16 mg and HCTZ 12.5mg DRUG

Single dose of FDC tablet formulation to be taken orally

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:

• Subjects Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
• Male and females aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.

You may not qualify if:

• Body weight \>=50kilograms (kg) and Body Mass Index (BMI) within the range 19 - 24.9kg / meter\^2 (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 per millilitre (MlU/mL) and estradiol \< 40 picograms per millilitre (pg/mL) (\<147 picomol per litre (pmol/L)) 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 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 enrolment. 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.
• A female subject is eligible to participate if she is of child-bearing potential with negative pregnancy test as determined by serum or urine Human Chorionic Gonadotropin (hCG) test at screening or prior to dosing AND 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.
• A female subject is eligible to participate if she 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.
• Alanine aminotransferase (ALT), 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 QT duration corrected for heart rate (QTc) of triplicate Electrocardiograms (ECGs) obtained over a brief recording period: QT duration corrected for heart rate by Fridericia's Formula (QTcF) \< 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. One unit is equivalent to 8 grams (g) 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 millimetre 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Hyderabad, 500 013, India

Location

Related Links

• Results for study 200957 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

Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

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 20, 2014
• First Posted: March 24, 2014
• Study Start: April 17, 2014
• Primary Completion: May 23, 2014
• Study Completion: May 23, 2014
• Last Updated: May 15, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share

Locations

IN (1)