Cardiovascular Disease
Conditions
Keywords
relative bio-availability, fasting, GW615775, Candesartan cilexetil, ATACAND
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.
Interventions
DRUGCandesartan Cilexetil in formulation 1
Round, biconvex white tablets containing Candesartan cilexetil 16 mg for oral administration
DRUGCandesartan Cilexetil in formulation 2
Round, biconvex white tablets containing Candesartan cilexetil 16 mg for oral administration
DRUGATACAND
Round, biconvex pink tablets containing Candesartan cilexetil 16 mg for oral administration
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* 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. * A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included only if the investigator in consultation with the Medical Monitor if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of pharmacokinetic (PK) parameters. | 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. | 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\[0-t\]). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Pharmacokinetic parameters to be estimated include: time of occurrence of Cmax (Tmax), terminal phase half-life (t1/2) and percentage of AUC(0-infinity) obtained by extrapolation (%AUCex). |
| Vital sign assessment as a safety measure | Up to 30 days | Vital sign assessment include: blood pressure and pulse rate measurements. |
| Number of subjects with adverse events as a safety measure | 50 days | Adverse events will be collected from the start of Study Treatment until the subject's final discharge from study at the end of Treatment Period 3, follow-up call or last outpatient visit, whichever is the latest. |
| Laboratory parameter assessment as a safety measure | Up to 30 days | Laboratory parameters include: hematology, clinical chemistry, urinalysis and additional parameters. |
Countries
India
Outcome results
None listed