Bioavailability Study of Candesartan Cilexetil 16mg Tablet Under Fasting Conditions

NCT02006602 | Completed Phase 1

• 1 other identifier: 201011
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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

Keywords

Candesartan cilexetil; Healthy adult human subjects; Bioequivalence

Outcome Measures

Primary Outcomes (1)

• Plasma pharmacokinetic (PK) parameters assessed by Cmax, AUC(0-infinity) and AUC(0-t)

  PK parameters include: Maximum observed concentration (Cmax), area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC\[0 infinity\]) and area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments \[AUC(0 t)\].

  Pre-dose, 0.5 hour (hr), 1 hr, 1.5 hr, 2 hr, 2.5 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 5.5 hr, 6 hr, 7 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr and 48 hr of each treatment period.

Secondary Outcomes (4)

• PK parameters assessed by tmax, %AUCex and t1/2

  Pre dose, 0.5 hr, 1 hr, 1.5 hr, 2 hr, 2.5 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 5.5 hr, 6 hr, 7 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr and 48 hr of each treatment period.

• Safety and tolerability assessment as assessed by adverse events (AEs)

  Up to 35 days

• Safety and tolerability assessment as assessed by vital signs

  Up to 35 days

• Safety and tolerability assessment as assessed by clinical laboratory values

  Up to 35 days

Study Arms (2)

Arm 1 reference then test

EXPERIMENTAL

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.

Drug: Candesartan cilexetil (GW615775, Test formulation); Drug: Candesartan cilexetil (Reference treatment)

Arm 2 test then reference

EXPERIMENTAL

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.

Drug: Candesartan cilexetil (GW615775, Test formulation); Drug: Candesartan cilexetil (Reference treatment)

Interventions

Candesartan cilexetil (GW615775, Test formulation) 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.

Arm 1 reference then test; Arm 2 test then reference

Candesartan cilexetil (Reference treatment) 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 1 reference then test; Arm 2 test then reference

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \>= 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Hyderabad, 500 013, India

Location

Related Links

• Results for study 201011 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Hypertension

Interventions

candesartan cilexetil

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

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: December 5, 2013
• First Posted: December 10, 2013
• Study Start: December 13, 2013
• Primary Completion: January 22, 2014
• Study Completion: January 22, 2014
• Last Updated: March 8, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will share

Locations

IN (1)