Bioequivalence Study of Nirmatrelvir & Ritonavir From Copaxid 150 +100 mg Tablets (Eva Pharma, Egypt) Versus Paxlovid 150 + 100 mg Film Coated Tablets (Pfizer Europe, Belgium)

Comparative Randomized, Single Dose, Three-way, Three-sequence, Two Treatment, Partial Replicate, Crossover, Open-label Study to Determine the Bioequivalence of Nirmatrelvir & Ritonavir From Copaxid 150 +100 mg Tablets (Eva Pharma, Egypt) Versus Paxlovid 150 + 100 mg Film Coated Tablets (Pfizer Europe, Belgium)

Comparative randomized, single dose, three-way, three-sequence, two treatment, partial replicate, crossover, open-label study to determine the bioequivalence of Nirmatrelvir & Ritonavir From Copaxid 150 +100 mg Tablets (Eva Pharma, Egypt) Versus Paxlovid 150 + 100 mg Film Coated Tablets (Pfizer Europe, Belgium)

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Nirmatrelvir 150 mg + Ritonavir 100 mg (Reference first dose); Drug: Nirmatrelvir 150 mg + Ritonavir 100 mg (test); Drug: Nirmatrelvir 150 mg + Ritonavir 100 mg (Reference second dose)

Detailed Description

Primary Pharmacokinetic Parameters: Cmax, 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): 28
• 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: 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, eg.: no history of heart, liver, kidney, gastrointestinal, nervous system, or metabolic abnormalities.
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. Females should be on a suitable birth control method.
6. Fully informed subjects that consented to participate in the study.

Exclusion Criteria:

1. Subjects with known allergy to the products tested.
2. Female subjects who were pregnant or nursing.
3. Acute infection within one week preceding first study drug administration.
4. History of drug or alcohol abuse.
5. Subject does not comply with the stated instruction of not taking any prescription or non-prescription drugs within two weeks before first study drug administration and until the end of the study.
6. Subject is on a special diet (for example subject is vegetarian).
7. 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.
8. 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.
9. Subject has a family history of severe diseases which have direct impact on the study.
10. Participation in a bioequivalence study or in a clinical study within the last 8 weeks before first study drug administration.
11. Subject intends to be hospitalized within 3 months after first study drug administration.
12. Subjects who have donated blood or lost more than 500 mL blood within 3 months prior to the study.

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: R reference (first dose); Reference drug (Paxlovid) Nirmatrelvir 150 mg + Ritonavir 100 mg tablets	Drug: Nirmatrelvir 150 mg + Ritonavir 100 mg (Reference first dose); 2 tablets from Nirmatrelvir 150 mg + 1 tablet from Ritonavir 100 mg; Other Names: Paxlovid
Experimental: T test; Test drug (Copaxid) Nirmatrelvir 150 mg + Ritonavir 100 mg tablets	Drug: Nirmatrelvir 150 mg + Ritonavir 100 mg (test); 2 tablets from Nirmatrelvir 150 mg + 1 tablet from Ritonavir 100 mg; Other Names: Copaxid
Active Comparator: R reference (second dose); Reference drug (Paxlovid) Nirmatrelvir 150 mg + Ritonavir 100 mg tablets	Drug: Nirmatrelvir 150 mg + Ritonavir 100 mg (Reference second dose); 2 tablets from Nirmatrelvir 150 mg + 1 tablet from Ritonavir 100 mg; Other Names: Paxlovid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximal measured plasma concentration	Up to 48 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 48 hours post dose in each treatment period

Collaborators and Investigators

• Sponsor: Genuine Research Center, Egypt
• Collaborators: Eva Pharma

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): August 21, 2022
• Primary Completion (Actual): September 4, 2022
• Study Completion (Actual): October 27, 2022

Study Registration Dates

• First Submitted: August 4, 2022
• First Submitted That Met QC Criteria: August 4, 2022
• First Posted (Actual): August 8, 2022

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 17, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir
• Other Study ID Numbers: GRC/1/22/1038

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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