Relative Bioavailability Study of Candesartan Cilexetil Under Fasting Conditions

NCT02254447 | Completed Phase 1

• 1 other identifier: 201713
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate the relative bioavailability of two candidate tablet formulations of 16 milligram (mg) Candesartan cilexetil (GW615775) compared with the reference product ATACAND™ containing 16 mg Candesartan cilexetil in healthy human subjects. This is an open-label, randomized, single dose, three-way crossover, six sequence study enrolling 18 healthy human subjects to ensure at least 14 subjects complete the study as planned. Each subject enrolled will participate in all three treatment periods and will be assigned to one of the six treatment sequences, in accordance with the randomization schedule. The treatment periods will be separated by a washout period of at least 7 days and no more than 14 days between dosing occasions. A follow up visit will be conducted 14-21 days post last dosing. ATACAND is a registered trademark of the AstraZeneca group of companies.

Conditions

Cardiovascular Disease

Keywords

relative bio-availability; fasting; GW615775; Candesartan cilexetil; ATACAND

Outcome Measures

Primary Outcomes (1)

• Composite of pharmacokinetic (PK) parameters.

  Pharmacokinetic parameters will be measured to estimate the relative bio-availability following administration of two candidate tablet formulations of Candesartan cilexetil relative to reference Candesartan cilexetil tablet. Pharmacokinetic parameters include: maximum observed concentration (Cmax), area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC\[0-infinite\]), Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC\[0-t\]).

  PK samples will be collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24, 36 and 48 hours post dose in each treatment period.

Secondary Outcomes (4)

• Plasma PK profile

  PK samples will be collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24, 36 and 48 hours post dose in each treatment period.

• Vital sign assessment as a safety measure

  Up to 30 days

• Number of subjects with adverse events as a safety measure

  50 days

• Laboratory parameter assessment as a safety measure

  Up to 30 days

Study Arms (6)

Sequence ABC

EXPERIMENTAL

Subjects in this arm will receive single dose of treatment A in period 1, treatment B in period 2 and treatment C in period 3 (one treatment per period), where treatment A= ATACAND as a reference treatment containing Candesartan cilexetil 16 mg, treatment B= Test formulation 1 containing Candesartan cilexetil 16 mg, and treatment C= Test formulation 2 containing Candesartan cilexetil 16 mg.

Drug: Candesartan Cilexetil in formulation 1; Drug: Candesartan Cilexetil in formulation 2; Drug: ATACAND

Sequence ACB

EXPERIMENTAL

Subjects in this arm will receive single dose of treatment A in period 1, treatment C in period 2 and treatment B in period 3 (one treatment per period), where treatment A= ATACAND as a reference treatment containing Candesartan cilexetil 16 mg, treatment B= Test formulation 1 containing Candesartan cilexetil 16 mg, and treatment C= Test formulation 2 containing Candesartan cilexetil 16 mg.

Drug: Candesartan Cilexetil in formulation 1; Drug: Candesartan Cilexetil in formulation 2; Drug: ATACAND

Sequence BAC

EXPERIMENTAL

Subjects in this arm will receive single dose of treatment B in period 1, treatment A in period 2 and treatment C in period 3 (one treatment per period), where treatment A= ATACAND as a reference treatment containing Candesartan cilexetil 16 mg, treatment B= Test formulation 1 containing Candesartan cilexetil 16 mg, and treatment C= Test formulation 2 containing Candesartan cilexetil 16 mg.

Drug: Candesartan Cilexetil in formulation 1; Drug: Candesartan Cilexetil in formulation 2; Drug: ATACAND

Sequence BCA

EXPERIMENTAL

Subjects in this arm will receive single dose of treatment B in period 1, treatment C in period 2 and treatment A in period 3 (one treatment per period), where treatment A= ATACAND as a reference treatment containing Candesartan cilexetil 16 mg, treatment B= Test formulation 1 containing Candesartan cilexetil 16 mg, and treatment C= Test formulation 2 containing Candesartan cilexetil 16 mg.

Drug: Candesartan Cilexetil in formulation 1; Drug: Candesartan Cilexetil in formulation 2; Drug: ATACAND

Sequence CAB

EXPERIMENTAL

Subjects in this arm will receive single dose of treatment C in period 1, treatment A in period 2 and treatment B in period 3 (one treatment per period), where treatment A= ATACAND as a reference treatment containing Candesartan cilexetil 16 mg, treatment B= Test formulation 1 containing Candesartan cilexetil 16 mg, and treatment C= Test formulation 2 containing Candesartan cilexetil 16 mg.

Drug: Candesartan Cilexetil in formulation 1; Drug: Candesartan Cilexetil in formulation 2; Drug: ATACAND

Sequence CBA

EXPERIMENTAL

Subjects in this arm will receive single dose of treatment C in period 1, treatment B in period 2 and treatment A in period 3 (one treatment per period), where treatment A= ATACAND as a reference treatment containing Candesartan cilexetil 16 mg, treatment B= Test formulation 1 containing Candesartan cilexetil 16 mg, and treatment C= Test formulation 2 containing Candesartan cilexetil 16 mg.

Drug: Candesartan Cilexetil in formulation 1; Drug: Candesartan Cilexetil in formulation 2; Drug: ATACAND

Interventions

Candesartan Cilexetil in formulation 1 DRUG

Round, biconvex white tablets containing Candesartan cilexetil 16 mg for oral administration

Sequence ABC; Sequence ACB; Sequence BAC; Sequence BCA; Sequence CAB; Sequence CBA

Candesartan Cilexetil in formulation 2 DRUG

Round, biconvex white tablets containing Candesartan cilexetil 16 mg for oral administration

Sequence ABC; Sequence ACB; Sequence BAC; Sequence BCA; Sequence CAB; Sequence CBA

ATACAND DRUG

Round, biconvex pink tablets containing Candesartan cilexetil 16 mg for oral administration

Sequence ABC; Sequence ACB; Sequence BAC; Sequence BCA; Sequence CAB; Sequence CBA

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.
• Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.

You may not qualify if:

• Body weight \>= 50 kilograms (kg) and Body Mass Index within the range 19 -24.9 kg/meter (m)\^2 (inclusive).
• Female subject: is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin test), not lactating, and at least one of the following conditions applies:
• Non-reproductive potential defined as: Pre-menopausal females with documented tubal ligation, or documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, or hysterectomy, or documented bilateral oophorectomy.
• Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone and estradiol levels consistent with menopause \[refer to laboratory reference ranges for confirmatory levels\]). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective 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.
• Reproductive potential and agrees to follow one of the options listed below in the GlaxoSmithKline (GSK) Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study medication and until \[at least five terminal half-lives OR until any continuing pharmacologic effect has ended, whichever is longer\] after the last dose of study medication and completion of the follow-up visit.
• GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in FRP. This list does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent from penilevaginal intercourse on a long term and persistent basis:
• Contraceptive subdermal implant that meets the effectiveness criteria including a \<1% rate of failure per year, as stated in the product label.
• Intrauterine device or intrauterine system that meets the standard operating procedure (SOP) effectiveness criteria including a \<1% rate of failure per year, as stated in the product label.
• Oral Contraceptive, either combined or progestogen alone. Injectable progestogen Contraceptive vaginal ring Percutaneous contraceptive patches Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject Male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository) only for the following 3 situations when there is a very low risk for developmental toxicity: Vaccines, Monoclonal antibodies when there is no target biology concern, Compounds that have a complete reproductive toxicology package and, have not shown any signal for developmental toxicity.
• The investigator is responsible for ensuring that subjects understand how to properly use the following methods of contraception. Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until \[at least five half-lives of study medication OR for a cycle of spermatogenesis following five terminal half-lives\] after the last dose of study medication: vasectomy with documentation of azoospermia, male condom plus partner use of one of the contraceptive options below:
• Contraceptive subdermal implant that meets the SOP effectiveness criteria including a \<1% rate of failure per year, as stated in the product label Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a \<1% rate of failure per year, as stated in the product label.
• Oral Contraceptive, either combined or progestogen alone Injectable progestogen Contraceptive vaginal ring Percutaneous contraceptive patches
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Alanine aminotransferase and bilirubin \>1.5x upper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Hyderabad, 500 013, India

Location

Related Links

• Results for study 201713 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Cardiovascular Diseases; Fasting

Interventions

candesartan cilexetil

Condition Hierarchy (Ancestors)

Feeding Behavior; Behavior

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2014
• First Posted: October 1, 2014
• Study Start: December 2, 2014
• Primary Completion: January 8, 2015
• Study Completion: January 8, 2015
• Last Updated: March 12, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will share

Locations

IN (1)