A Study of Sofosbuvir and Ledipasvir From Soviredia 90/400 mg Tablets (Minapharm, Egypt) Versus Harvoni 90/400 mg Tablets (Gilead Sciences, USA)

Open Label Randomized, Single Dose, Three Way Three Sequence Two Treatment Partial Replicate Crossover Bioequivalence Study of Sofosbuvir and Ledipasvir From Soviredia 90/400 mg Tablets (Minapharm, Egypt) Versus Harvoni 90/400 mg Tablets (Gilead Sciences, USA)

Comparative randomized, single dose, three way three sequence two treatment partial replicate crossover open-label study to determine the bioequivalence of Sofosbuvir and Ledipasvir from Soviredia 90/400 mg Tablets (Minapharm, Egypt) Versus Harvoni 90/400 mg Tablets (Gilead Sciences, USA) in Healthy Human Volunteers Under Fasting Condition.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Soviredia; Drug: Harvoni (first dose); Drug: Harvoni (Second dose)

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): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11757
    • Genuine Research Center GRC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• 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

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: B reference (first dose); Reference drug (Harvoni) 1 tablet contains 400 mg Sofosbuvir and 90 mg Ledipasvir	Drug: Harvoni (first dose); Reference drug (Harvoni) 1 tablet contains 400 mg Sofosbuvir and 90 mg Ledipasvir; Other Names: Harvoni
Active Comparator: B reference (second dose); Reference drug (Harvoni) 1 tablet contains 400 mg Sofosbuvir and 90 mg Ledipasvir	Drug: Harvoni (Second dose); Reference drug (Harvoni) 1 tablet contains 400 mg Sofosbuvir and 90 mg Ledipasvir; Other Names: Harvoni
Experimental: T test; Test drug (Soviredia)1 tablet contains 400 mg Sofosbuvir and 90 mg Ledipasvir	Drug: Soviredia; Test drug (Soviredia)1 tablet contains 400 mg Sofosbuvir and 90 mg Ledipasvir; Other Names: Harvoni

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal measured plasma concentration (Cmax)	Serial blood samples for determination of study drug will be collected at 0.00, 0.166, 0.33, 0.50, 0.75, 1.00, 1.33, 1.66, 2.00, 2.50, 3.00, 4.00, 6.00, 7.00 , 9.00, 12.00, 24.00, 48.00 and 72.00 hours	Up to 72 hours post dose in each treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of the maximum plasma concentration (Tmax)	The amount of time that a drug is present at the maximum concentration in serum	Up to 72 hours post dose in each treatment period

Collaborators and Investigators

• Sponsor: Genuine Research Center, Egypt
• Collaborators: MinaPharm Pharmaceuticals
• Investigators: Study Chair: Ahmed Elshafeey, Ph.D. Pharma, Genuine Research Center

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

• Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95) The European Agency for the Evaluation of Medicinal Products (EMEA) May 1997
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2017
• Primary Completion (Actual): May 13, 2017
• Study Completion (Actual): May 28, 2017

Study Registration Dates

• First Submitted: June 19, 2017
• First Submitted That Met QC Criteria: July 30, 2019
• First Posted (Actual): July 31, 2019

Study Record Updates

• Last Update Posted (Actual): July 31, 2019
• Last Update Submitted That Met QC Criteria: July 30, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiviral Agents; Ledipasvir, sofosbuvir drug combination
• Other Study ID Numbers: GRC/1/17/635

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes