Bioequivalence Study of Solifenacin Succinate & Mirabegron From Mirfenacin MR 5/50 mg Extended Release Tablets (Hikma Pharma, Egypt) Versus Vesicare 5 mg FCT & Betmiga 50 mg Prolonged-Release Tablets (Astellas Pharma Europe B.V, the Netherlands / Astellas Pharma Europe B.V, the Netherlands)

An Open Label Randomized, Single Dose, Three-way, Partial Replicate Bioequivalence Study to Determine the Bioequivalence of Solifenacin Succinate & Mirabegron From Mirfenacin MR 5/50 mg Extended Release Tablets (Hikma Pharma, Egypt) Versus Vesicare 5 mg Film Coated Tablets & Betmiga 50 mg Prolonged-Release Tablets (Astellas Pharma Europe B.V, the Netherlands / Astellas Pharma Europe B.V, the Netherlands)

An open label randomized, single dose, three-way, partial replicate bioequivalence study to determine the bioequivalence of Solifenacin Succinate & Mirabegron From Mirfenacin MR 5/50 mg Extended Release Tablets (Hikma Pharma, Egypt) Versus Vesicare 5 mg Film Coated Tablets & Betmiga 50 mg Prolonged-Release Tablets (Astellas Pharma Europe B.V, the Netherlands / Astellas Pharma Europe B.V, the Netherlands)

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Vesicare (Solifenacin Succinate 5 mg) & Betmiga (Mirabegron 50 mg) (Reference first dose); Drug: Mirfenacin MR (Solifenacin Succinate 5 mg & Mirabegron 50 mg) (Test); Drug: Vesicare (Solifenacin Succinate 5 mg) & Betmiga (Mirabegron 50 mg) (Reference second dose)

Detailed Description

Healthy volunteers, 18-55 years of age, selected from the Egyptian population fulfilling the selection criteria. 30 Healthy volunteers (28 volunteers + 2 extra volunteers to compensate for drop-outs) will participate in the study. All dosed subject samples will be analyzed and their data will be included in the final study report.

For Solifenacin:

Primary Pharmacokinetic Parameters: Cmax and truncated AUC0→72 Secondary Pharmacokinetic Parameters: Tmax

For Mirabegron:

Primary Pharmacokinetic Parameters: Cmax, AUC0→t and AUC0→∞ Secondary Pharmacokinetic Parameters: Ke, tmax and t1/2e. ANOVA using 5% significance level for log transformed (with the 90% confidence intervals), untransformed data of Cmax, AUC0→t and AUC0→∞ and for untransformed data of Ke, tmax and t1/2e, for Mirabegron and untransformed data of Cmax and truncated AUC0→t and for untransformed data of tmax for Solifenacin.

• 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 (18.5-30.0) 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. Subjects who meet any of the contraindications to the administration of Solifenacin succinate and/or Mirabegron.
3. Subject does not agree not to consume any medication or food which may affect CYP3A4 enzyme at least two weeks prior to first study drug administration until donating the last sample of the study.
4. Subjects that do not agree not to consume alcohol-containing beverages and foods for 2 weeks before dosing and throughout the period of sample collection.
5. Heavy smokers.
6. Female subjects who were pregnant or nursing.
7. Acute infection within one week preceding first study drug administration.
8. History of drug or alcohol abuse.
9. 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.
10. Subject is on a special diet (for example subject is vegetarian).
11. 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.
12. Subject does not agree not to consume any beverages or foods containing grapefruit 14 days prior to first study drug administration until the end of the study.
13. Subject has a family history of severe diseases which have direct impact on the study.
14. Participation in a bioequivalence study or in a clinical study within the last 8 weeks before first study drug administration.
15. Subject intends to be hospitalized within 3 months after first study drug administration.
16. Subjects who have blood donated 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 drugs (Vesicare & Betmiga)	Drug: Vesicare (Solifenacin Succinate 5 mg) & Betmiga (Mirabegron 50 mg) (Reference first dose); 1 tablet Vesicare contains Solifenacine succinate 5 mg & 1 tablet Betmiga contains Mirabegron 50 mg orally administrated followed by 240 ml of water; Other Names: Vesicare & Betmiga
Experimental: T test; Test drug (Mirfenacin MR)	Drug: Mirfenacin MR (Solifenacin Succinate 5 mg & Mirabegron 50 mg) (Test); 1 tablet Mirfenacin MR contains Solifenacine succinate 5 mg & Mirabegron 50 mg orally administrated followed by 240 ml of water; Other Names: Mirfenacin MR
Active Comparator: R reference (second dose); Reference drugs (Vesicare & Betmiga)	Drug: Vesicare (Solifenacin Succinate 5 mg) & Betmiga (Mirabegron 50 mg) (Reference second dose); 1 tablet Vesicare contains Solifenacine succinate 5 mg & 1 tablet Betmiga contains Mirabegron 50 mg orally administrated followed by 240 ml of water; Other Names: Vesicare & Betmiga

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
For Solifenacin: Cmax	to measure the maximal measured plasma concentration	Up to 72 hours post dose in each treatment period
For Solifenacin: truncated AUC0→72	to measure truncated area under the curve from zero time to 72 hours	Up to 72 hours post dose in each treatment period
For Mirabegron: Cmax	to measure the maximal measured plasma concentration	Up to 240 hours post dose in each treatment period
For Mirabegron: AUC0→t	to measure the area under the curve from zero time to 240 hours	Up to 240 hours post dose in each treatment period
For Mirabegron: AUC0→∞	to measure the area under the curve from zero time to infinity	Up to 240 hours post dose in each treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
For Solifenacin & Mirabegron: Tmax	Time of the maximum plasma concentration	For Solifenacin:Up to 72 hours post dose in each treatment period & For Mirabegron:Up to 240 hours post dose in each treatment period

Collaborators and Investigators

• Sponsor: Genuine Research Center, Egypt
• Collaborators: Hikma 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 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.
• Description: 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 (Actual): May 30, 2022
• Primary Completion (Actual): July 25, 2022
• Study Completion (Actual): October 25, 2022

Study Registration Dates

• First Submitted: February 21, 2023
• First Submitted That Met QC Criteria: March 2, 2023
• First Posted (Actual): March 14, 2023

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: March 2, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Adrenergic beta-3 Receptor Agonists; Mirabegron; Solifenacin Succinate
• Other Study ID Numbers: GRC/1/21/998

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