Hypertension
Conditions
Keywords
Bioequivalence, Candesartan cilexetil, Healthy adult human subjects
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 an 8mg test formulation tablet of candesartan cilexetil (GW615775) compared to an 8mg reference tablet of candesartan cilexetil in healthy adult subjects. ATACAND is a registered trademark of the AstraZeneca group of companies.
Interventions
Test formulation candesartan cilexetil 8 mg will be supplied as round, biconvex pink tablets with PX 8 embossed in one face.
Reference treatment of candesartan cilexetil 8 mg will be supplied as round, biconvex pink tablets, scored in one face and with embossment in both faces (008 embossment in the plain face and A CG in the scored face).
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
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 a responsible and experienced physician, 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 GSK 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 \>= 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 visit.or 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) .
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma pharmacokinetic (PK) parameters assessed by Cmax, AUC(0-infinity) and 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. | 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 \[AUC(0-t)\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | PK parameters include: Percentage of AUC(0-infinity) obtained by extrapolation (%AUCex), time of occurrence of Cmax (tmax), terminal phase half-life (t1/2). |
| 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 | Vital sign measurements will include systolic and diastolic blood pressure, and pulse rate. |
| Safety and tolerability assessment as assessed by clinical laboratory values | Up to 35 days | Clinical laboratory assessments will include hematology, clinical chemistry, routine urinalysis and additional parameters. |
Countries
India
Outcome results
None listed