A Bioequivalence Study of Amlodipine / Valsartan From Amlodipine/Valsartan 10/160 Tablets (Pharmacare, Palestine) and Exforge Tablets (Novartis Pharma, USA)

Comparative Open-label,Randomized, Fasting, Single Dose, Two-way Crossover Bioequivalence Study of Amlodipine / Valsartan From Amlodipine/Valsartan 10/160 Tablets (Pharmacare, Palestine) and Exforge Tablets (Novartis Pharma, USA)

Comparative randomized, single dose, two-way crossover open-label study to determine the bioequivalence of Amlodipine / valsartan from Amlodipine/Valsartan 10/160 film coated tablets (Pharmacare, Palestine) and Exforge 10/160 film coated tablets (Novartis Pharma, USA).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Amlodipine/Valsartan; Drug: Exforge

Detailed Description

Primary Pharmacokinetic Parameters: Cmax, Area under cover (AUC0→t and AUC0→∞ ) Secondary Pharmacokinetic Parameters: Ke, tmax and t1/2e. ANOVA using 5% significance level for transformed (with the 90% confidence intervals) and untransformed data of Cmax, AUC0→t and AUC0→∞ and for untransformed data of Ke, tmax and t1/2e. The confidence intervals of logarithmically transformed Test/Reference ratios for Cmax, AUC0→t and AUC0→∞ to be within 80.00-125.00%.

A comprehensive final report will be issued upon the completion of the study.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Genuine Research Center GRC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy male or female, age 18 to 55 years, inclusive.
2. Body weight within 15% of normal range according to the accepted normal values for body mass index (BMI).
3. Medical demographics without evidence of clinically significant deviation from normal medical condition.
4. Results of clinical laboratory test are within the normal range or with a deviation that is not considered clinically significant by principal investigator.
5. Subject does not have allergy to the drugs under investigation.

Exclusion Criteria:

1. Subjects with known allergy to the products tested.
2. Subjects whose values of BMI were outside the accepted normal ranges.
3. Female subjects who were pregnant, nursing or taking birth control pills.
4. Medical demographics with evidence of clinically significant deviation from normal medical condition.
5. Results of laboratory tests which are clinically significant.
6. Acute infection within one week preceding first study drug administration.
7. History of drug or alcohol abuse.
8. Subject does not agree not to take any prescription or non-prescription drugs within two weeks before first study drug administration and until the end of the study.
9. Subject is on a special diet (for example subject is vegetarian).
10. Subject does not agree not to consume any beverages or foods containing methyl-xanthenes e.g. caffeine (coffee, tea, cola, chocolate etc.) 48 hours prior to the study administration of either study period until donating the last sample in each respective period.
11. Subject does not agree not to consume any beverages or foods containing grapefruit 7 days prior to first study drug administration until the end of the study.
12. Subject has a history of severe diseases which have direct impact on the study.
13. Participation in a bioequivalence study or in a clinical study within the last 6 weeks before first study drug administration.
14. Subject intends to be hospitalized within 3 months after first study drug administration.
15. Subjects who, through completion of this study, would have donated more than 500 ml of blood in 7 days, or 750 ml of blood in 30 days, 1000 ml in 90 days, 1250 ml in 120 days, 1500 ml in 180 days, 2000 ml in 270 days, 2500 ml of blood in 1 year.

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: A Test; Test drug (Amlodipine/Valsartan) 1 tablet contains Amlodipine 10 mg & valsartan 160 mg	Drug: Amlodipine/Valsartan; 1 tablet contains Amlodipine 10 mg &valsartan 160 mg; Other Names: Exforge
Active Comparator: B Reference; Reference drug (Exforge) 1 tablet contains Amlodipine 10 mg & valsartan 160 mg	Drug: Exforge; 1 tablet contains Amlodipine 10 mg &valsartan 160 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Bioequivalence based on Cmax	Up to 72 hours post dose in each treatment period
Bioequivalence based on AUC parameters	Up to 72 hours post dose in each treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with adverse events (AE)s	Safety and tolerability parameters will include recording of AEs	Up to 72 hours post dose in each treatment period
Safety assessed by vital sign measurement	Vital sign measurement will include blood pressure, pulse rate, respiration rate and body temperature	Up to 72 hours post dose in each treatment period
Measure of clinical laboratory test values to access safety and tolerability	Clinical laboratory tests will include hematology, clinical chemistry and urinalysis	Up to 72 hours post dose in each treatment period

Collaborators and Investigators

• Sponsor: Genuine Research Center, Egypt
• Collaborators: Pharmacare PLC, Palestine

Publications and helpful links

General Publications

• Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability. J Pharmacokinet Biopharm. 1987 Dec;15(6):657-80. doi: 10.1007/BF01068419.
• Chow SC, Wang H. On sample size calculation in bioequivalence trials. J Pharmacokinet Pharmacodyn. 2001 Apr;28(2):155-69. doi: 10.1023/a:1011503032353. Erratum In: J Pharmacokinet Pharmacodyn. 2002 Feb;29(1):101.
• Diletti E, Hauschke D, Steinijans VW. Sample size determination for bioequivalence assessment by means of confidence intervals. Int J Clin Pharmacol Ther Toxicol. 1991 Jan;29(1):1-8.

Helpful Links

• International conference of Harmonization (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonized Tripartite Guideline. Guidelines for Validation of Analytical Procedures: Methodology. November, 1996
• Note for Guidance on Clinical Safety Data Management; Definitions And Standards for Expedited Reporting (CPMP/ICH/377/95) The European Agency for the Evaluation of Medicinal Products (EMEA) June 1995.
• Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95) The European Agency for the Evaluation of Medicinal Products (EMEA) May 1997

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: July 30, 2015
• First Submitted That Met QC Criteria: August 5, 2015
• First Posted (Estimate): August 10, 2015

Study Record Updates

• Last Update Posted (Estimate): August 10, 2015
• Last Update Submitted That Met QC Criteria: August 5, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Amlodipine; Valsartan; Amlodipine, Valsartan Drug Combination
• Other Study ID Numbers: GRC/1/10/01 CAREPALST