Study to Determine the Bioequivalence of Two Products Containing Rosuvastatin (20 mg/Tablet)

A Pivotal, Open-label, Balanced, Randomised, Two-treatment, Two-sequence, Two-period, Two-way Crossover, Single Oral Dose Bioequivalence Study of Rosuvastatin/ Verisfield 20 mg Film-coated Tablets Versus Crestor/ AstraZeneca 20 mg Film-coated Tablets in Healthy Adults Under Fasting Conditions

The purpose of this study is to determine the bioequivalence of Rosuvastatin/ Verisfield 20 mg film-coated tablets and Crestor™/ AstraZeneca 20 mg film-coated tablets.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Rosuvastatin 20 mg film-coated tablets; Drug: Crestor 20 mg film-coated tablets

Detailed Description

This study aims to compare the absorption and disposition kinetics of two products containing rosuvastatin under fasting conditions. These products are: Rosuvastatin/ Verisfield 20 mg film-coated tablets, a Test product manufactured by HELP S.A., Greece and Crestor™/ AstraZeneca 20 mg film-coated tablets, a Reference product manufactured by AstraZeneca, UK. The bioequivalence of a single 20 mg dose of both products will be assessed by comparing the pharmacokinetic parameters derived from the plasma concentration-time profiles for rosuvastatin.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• India
  • Gujarat
    • Ahmedabad, Gujarat, India, 380056
      • Synchron Research Services Pvt. Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Willingness to provide informed consent to participate in the study.
• Comprehension of the nature and purpose of the study and willingness to comply with the requirements of the entire procedure.
• Healthy adult, human Indian volunteers within the age range of 18 to 45 years (both inclusive).
• Body Mass Index (BMI) ≥ 18.50 kg/m2 to ≤ 30.00 kg/m2.
• Hemoglobin: ≥12.0 gm% for male and ≥11.5 gm% for female.
• Absence of disease markers of HIV I & II, HBsAg, HCVAb and P24 antigen test.
• Females of childbearing age must be practicing an acceptable form of birth control for at least six months before screening, unless they have had bilateral oophorectomy or tubal ligation or their male partner has had vasectomy.
• Females of childbearing age agree to use acceptable form of birth control during the study and until the drug is washed out from the body, i.e. at least 14 days after last dosing, unless they have had bilateral oophorectomy or tubal ligation or their male partner has had vasectomy.
• Absence of significant disease or clinically significant abnormal laboratory values during the laboratory evaluations.
• Absence of any diseases in medical history or physical examination during the screening.
• Have a normal 12-lead ECG or one with abnormality considered clinically insignificant.
• Have a normal chest X-ray (P. A. view).
• Non smokers (since last six months)
• Negative serum β-HCG at the time of screening (for females only)

Exclusion Criteria:

• History / evidence of allergy or hypersensitivity to rosuvastatin or to any of the excipients or to any other drug.
• Any major illness within the last three months or any significant ongoing chronic medical illness.
• History of or active liver or kidney disease.
• History of or active deep vein thrombosis and thromboembolic disorders.
• History of breast cancer, endometrial cancer or other estrogen-dependent neoplasia, endometriosis and undiagnosed vaginal bleeding (for females only).
• History of drug abuse (including barbiturates, benzodiazepines, opioids, cocaine, cannabinoids and amphetamine etc.) within the last three months.
• History of neuropsychiatric diseases.
• History of hypothyroidism.
• Personal or family history of hereditary muscular disorders.
• History of myopathy.
• History of myalgia.
• History of rhabdomyolysis.
• History of alcohol abuse.
• History of proteinuria.
• Asian population (except Indian).
• History of interstitial lung disease.
• History of or current gastro-intestinal diseases influencing drug absorption.
• History of alcoholism (more than two years), moderate drinkers (more than three drinks per day).
• Participation in any clinical trial within last three months.
• History of difficulty with donating blood or difficulty in accessibility of veins in left or right arm.
• Donation of blood (one unit or 350 mL or more) within last three months.
• Use of any prescription drug therapy within last two weeks and over the counter (OTC) drugs or herbal products within last one week.
• Pregnant women.
• Breast feeding women.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Product; Rosuvastatin 20 mg film-coated tablets	Drug: Rosuvastatin 20 mg film-coated tablets; Single oral dose of 20 mg
Active Comparator: Reference product; Crestor 20 mg film-coated tablets	Drug: Crestor 20 mg film-coated tablets; Single oral dose of 20 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration (AUC0-t) from zero (0) hours to time (t)	The area under the plasma concentration versus time curve, from time zero (0) to t hours	Before dosing (0 hour) and 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 4.50, 5.00, 6.00, 7.00, 8.00, 10.00, 12.00, 16.00, 24.00, 36.00 and 48.00 hours post-dose
Maximum concentration (Cmax)	Maximum measured plasma concentration	Before dosing (0 hour) and 0.25, 0.50, 0.75, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 4.50, 5.00, 6.00, 7.00, 8.00, 10.00, 12.00, 16.00, 24.00, 36.00 and 48.00 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to maximum concentration (Tmax)	Time of the maximum measured plasma concentration. If the maximum value occurs at more than one time point, tmax is defined as the first time point with this value	Before dosing (0 hour) and 0.25, 0.50, 0.75, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 4.50, 5.00, 6.00, 7.00, 8.00, 10.00, 12.00, 16.00, 24.00, 36.00 and 48.00 hours post-dose
Elimination rate constant (Kel)	Apparent first-order elimination or terminal rate constant	Before dosing (0 hour) and 0.25, 0.50, 0.75, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 4.50, 5.00, 6.00, 7.00, 8.00, 10.00, 12.00, 16.00, 24.00, 36.00 and 48.00 hours post-dose
Terminal half life (t1/2)	The elimination or terminal half-life	Before dosing (0 hour) and 0.25, 0.50, 0.75, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 4.50, 5.00, 6.00, 7.00, 8.00, 10.00, 12.00, 16.00, 24.00, 36.00 and 48.00 hours post-dose
Area under the plasma concentration (AUC0-infinity) from zero (0) hours to infinity	The area under the plasma concentration versus time curve from time (0) to infinity	Before dosing (0 hour) and 0.25, 0.50, 0.75, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 4.50, 5.00, 6.00, 7.00, 8.00, 10.00, 12.00, 16.00, 24.00, 36.00 and 48.00 hours post-dose
Number of participants with Adverse Events		6 days

Collaborators and Investigators

• Sponsor: Verisfield UK Ltd. Greek Branch
• Investigators: Principal Investigator: Kathiria Jayesh, M.D., Synchron Research Services Pvt. Ltd.

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: May 9, 2016
• First Submitted That Met QC Criteria: May 9, 2016
• First Posted (Estimate): May 10, 2016

Study Record Updates

• Last Update Posted (Estimate): July 6, 2016
• Last Update Submitted That Met QC Criteria: July 4, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Bioequivalence; two rosuvastatin-containing products
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: ROS/2016/1278