Relative Bioavailability Study of One Amlodipine 10mg Tablet and One Rosuvastatin 20mg Tablet to Two Fixed Dose Combinations of Amlodipine (10mg) and Rosuvastatin (20mg) in Healthy Subjects Under Fasting Conditions

NCT02075619 | Completed Phase 1

• 1 other identifier: 200561
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension

Keywords

Amlodipine; Healthy volunteers; Rosuvastatin; Dyslipidaemia; Pharmacokinetics; Hypertension

Outcome Measures

Primary Outcomes (1)

• Plasma pharmacokinetics (PK) parameters of amlodipine and rosuvastatin following single dose administration

  PK parameters include: area under the plasma concentration curve (AUC\[0-infinity\], AUC\[0-t\]), maximum observed concentration (Cmax).

  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

Secondary Outcomes (5)

• 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

• Safety as assessed by adverse events

  Up to 58 days

• Safety as assessed by vital signs

  Up to 58 days

• Safety as assessed by clinical laboratory safety data

  Up to 58 days

• Safety as assessed by Electrocardiogram (ECG) parameters

  Up to 58 days

Study Arms (6)

Sequence 1

EXPERIMENTAL

Four subjects (2 Chinese and 2 Caucasian) will receive one amlodipine 10mg tablet and one rosuvastatin 20mg tablet in Period 1; one GSK3074477 Fixed dose combination (FDC) formulation-1 tablet in Period 2 and one GSK3074477 FDC formulation-2 tablet in Period 3; all treatments will be administered orally in fasted state. The three treatment periods will be separated by a washout period of between 12-17 days.

Drug: Amlodipine+Rosuvastatin; Drug: GSK3074477 FDC - 1; Drug: GSK3074477 FDC - 2

Sequence 2

EXPERIMENTAL

Four subjects (2 Chinese and 2 Caucasian) will receive one amlodipine 10mg tablet and one rosuvastatin 20mg tablet in Period 1; one GSK3074477 FDC formulation-2 tablet in Period 2 and one GSK3074477 FDC formulation-1 tablet in Period 3; all treatments will be administered orally in fasted state. The three treatment periods will be separated by a washout period of between 12-17 days.

Drug: Amlodipine+Rosuvastatin; Drug: GSK3074477 FDC - 1; Drug: GSK3074477 FDC - 2

Sequence 3

EXPERIMENTAL

Four subjects (2 Chinese and 2 Caucasian) will receive one GSK3074477 FDC formulation-1 tablet in Period 1, one amlodipine 10mg tablet and one rosuvastatin 20mg tablet in Period 2; and one GSK3074477 FDC formulation-2 tablet in Period 3; all treatments will be administered orally in fasted state. The three treatment periods will be separated by a washout period of between 12-17 days.

Drug: Amlodipine+Rosuvastatin; Drug: GSK3074477 FDC - 1; Drug: GSK3074477 FDC - 2

Sequence 4

EXPERIMENTAL

Four subjects (2 Chinese and 2 Caucasian) will receive one GSK3074477 FDC formulation-1 tablet in Period 1; one GSK3074477 FDC formulation-2 tablet in Period 2; and one amlodipine 10mg tablet and one rosuvastatin 20mg tablet in Period 3; all treatments will be administered orally in fasted state. The three treatment periods will be separated by a washout period of between 12-17 days.

Drug: Amlodipine+Rosuvastatin; Drug: GSK3074477 FDC - 1; Drug: GSK3074477 FDC - 2

Sequence 5

EXPERIMENTAL

Four subjects (2 Chinese and 2 Caucasian) will receive one GSK3074477 FDC formulation-2 tablet in Period 1; one amlodipine 10mg tablet and one rosuvastatin 20mg tablet in Period 2; and one GSK3074477 FDC formulation-1 tablet in Period 3; all treatments will be administered orally in fasted state. The three treatment periods will be separated by a washout period of between 12-17 days.

Drug: Amlodipine+Rosuvastatin; Drug: GSK3074477 FDC - 1; Drug: GSK3074477 FDC - 2

Sequence 6

EXPERIMENTAL

Four subjects (2 Chinese and 2 Caucasian) will receive one GSK3074477 FDC formulation-2 tablet in Period 1; one GSK3074477 FDC formulation-1 tablet in Period 2; and one amlodipine 10mg tablet and one rosuvastatin 20mg tablet in Period 3; all treatments will be administered orally in fasted state. The three treatment periods will be separated by a washout period of between 12-17 days.

Drug: Amlodipine+Rosuvastatin; Drug: GSK3074477 FDC - 1; Drug: GSK3074477 FDC - 2

Interventions

Amlodipine+Rosuvastatin DRUG

Amlodipine 10mg will be supplied as white or off-white, emerald shaped tablet. Rosuvastatin 20mg will be supplied as pink round film coated tablet.

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

GSK3074477 FDC - 1 DRUG

GSK3074477 containing combination of 10mg amlodipine and 20mg rosuvastatin, will be supplied as white caplet shaped film coated tablet.

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

GSK3074477 FDC - 2 DRUG

GSK3074477 containing combination of 10mg amlodipine and 20mg rosuvastatin, will be supplied as white caplet shaped film coated tablet.

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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. More than 2 standard drinks a day for a woman, and more than 3 drinks a day (about 30 gram \[g\] of alcohol) for a man, and more than 4 days per week. One standard drink contains 10g of pure alcohol and is equivalent to a can of beer (220 milliliter \[mL\]), 1 glass of wine (100mL), or 1 nip (30mL) 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.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• A systolic blood pressure \<95 millimeter of mercury (mmHg) or a recent history of postural symptoms.
• 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.
• A positive test for Human Immunodeficiency Virus (HIV) antibody.
• Pregnant females as determined by positive urine hCG test at Day -1 or serum hCG at screening visit.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• SingHealth Investigational Medicine Unit, Singapore: collaborator

Study Sites (1)

GSK Investigational Site

Singapore, 169608, Singapore

Location

Related Links

• Results for study 200561 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Hypertension; Dyslipidemias

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic 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: February 27, 2014
• First Posted: March 3, 2014
• Study Start: March 24, 2014
• Primary Completion: July 11, 2014
• Study Completion: July 11, 2014
• Last Updated: May 10, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share

Locations

SG (1)