Hypertension
Conditions
Keywords
Amlodipine, Healthy volunteers, Rosuvastatin, Dyslipidaemia, Pharmacokinetics, Hypertension
Brief summary
This is an open-label, single-centre, randomized, single dose, three-way crossover, six sequence study to evaluate the comparative bioavailability of two Fixed Dose Combination (FDC) tablet formulations of amlodipine and rosuvastatin relative to innovator samples under fasting conditions, in healthy adult subjects. Subjects will be 12 Chinese and 12 Caucasian subjects living in Singapore. The randomisation will be stratified by ethnicity to ensure an equal number of subjects will be assigned to each dosing sequence. Subjects will receive each of the following three treatments administered in a randomized three-way crossover design: a reference treatment consisting of a single 10mg amlodipine tablet and 20mg rosuvastatin tablet ; a single fixed dose combination tablet consisting of 10mg amlodipine and 20mg rosuvastatin (Test Formulation - FDC 1); and another single fixed dose combination tablet consisting of 10mg amlodipine and 20mg rosuvastatin (Test Formulation - FDC 2). Two test formulations have same active pharmaceutical ingredients (amlodipine and rosuvastatin), same doses and different inactive ingredients. Each subject will participate in three treatment periods. The study consists of a screening phase, three treatment periods and a follow-up visit. The three treatment periods will be separated by a washout period of 12-17 days.
Interventions
DRUGAmlodipine+Rosuvastatin
Amlodipine 10mg will be supplied as white or off-white, emerald shaped tablet. Rosuvastatin 20mg will be supplied as pink round film coated tablet.
DRUGGSK3074477 FDC - 1
GSK3074477 containing combination of 10mg amlodipine and 20mg rosuvastatin, will be supplied as white caplet shaped film coated tablet.
DRUGGSK3074477 FDC - 2
GSK3074477 containing combination of 10mg amlodipine and 20mg rosuvastatin, will be supplied as white caplet shaped film coated tablet.
Sponsors
SingHealth Investigational Medicine Unit, Singapore
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female between 21 and 65 years of age inclusive, at the time of signing the informed consent. * Alanine transaminase, alkaline phosphatase and total bilirubin \<=1.5x upper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * Normal electrocardiogram (ECG) morphology and measurements. Single corrected QT interval (QTc) \<450 milliseconds (msec). In particular QTc \<450 msec or QT \<480 msec in subjects with Bundle Branch Block based on an average from three ECGs obtained over a brief recording period. * 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 parameters 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 and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * 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 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 \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \>40 milli-international units per milliliter (MIU/mL) and estradiol \<40 picograms per milliliter (pg/mL) (\<147 picomole per liter) is confirmatory\]; On hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use a protocol approved contraception method 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 or urine human chorionic gonadotropin (hCG) test at the 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 the 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 14 days after last dose of amlodipine/rosuvastatin, i.e. after single dose of treatment period 3. * Male subjects with female partners of child-bearing potential must agree to use one of the contraceptive methods and not to donate sperm. These criteria must be followed from the time of the first dose of study medication until the follow-up contact visit. * Body weight \>=50 kilogram (kg) and body mass index (BMI) within the range 18.5 - 29.9 kilogram per square meter (kg/m\^2) (inclusive). * Chinese or Caucasian self-reported by the subjects for both parents and all 4 grandparents. The ethnic group is as defined by National Registration Identity Cards provided additional confirmation of ethnicity. * 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 |
|---|---|---|
| Plasma pharmacokinetics (PK) parameters of amlodipine and rosuvastatin following single dose administration | Pre dose, 15 minute [min], 30 min, 1 hour [hr], 2hr, 3hr, 4hr, 5hr, 6 hr, 8 hr, 10 hr, 12 hr, 18hr, 24hr, 36 hr, 48 hr, 72 hr and 96 hr post dose of each treatment period | PK parameters include: area under the plasma concentration curve (AUC\[0-infinity\], AUC\[0-t\]), maximum observed concentration (Cmax). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Additional PK parameters of amlodipine and rosuvastatin following single dose administration | Pre dose, 15 minute [min], 30 min, 1 hour [hr], 2hr, 3hr, 4hr, 5hr, 6 hr, 8 hr, 10 hr, 12 hr, 18hr, 24hr, 36 hr, 48 hr, 72 hr and 96 hr post dose of each treatment period | PK parameters include: time to maximum observed concentration (tmax), terminal half-life (t1/2). |
| Safety as assessed by adverse events | Up to 58 days | — |
| Safety as assessed by vital signs | Up to 58 days | Vital sign measurements include systolic and diastolic blood pressure, temperature, pulse rate and respiratory rate. |
| Safety as assessed by clinical laboratory safety data | Up to 58 days | Laboratory testing includes hematology, clinical chemistry and urinalysis. |
| Safety as assessed by Electrocardiogram (ECG) parameters | Up to 58 days | Single 12-lead ECGs will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT interval. |
Countries
Singapore
Outcome results
None listed