Bioequivalence Study of Fingolimod From Sphingomod 0.5 mg Hard Gelatin Capsules (Hikma Pharma, Egypt) Versus Gilenya 0.5 mg Hard Capsules (Novartis Pharma AG, Basle, Switzerland).

• ClinicalTrials.gov Identifier: NCT04657744
• Recruitment Status: Completed
• First Posted: December 8, 2020
• Last Update Posted: December 8, 2020
• Sponsor: Genuine Research Center, Egypt
• Collaborator: Hikma Pharmaceuticals LLC
• Information provided by (Responsible Party): Genuine Research Center, Egypt

Study Description

Brief Summary:

An open label randomized, single dose, two-way crossover bioequivalence study to determine the bioequivalence of Fingolimod From Sphingomod 0.5 mg Hard Gelatin Capsules (Hikma Pharma, Egypt) Versus Gilenya 0.5 mg Hard Capsules (Novartis Pharma AG, Basle, Switzerland) in Healthy Human Volunteers Under Fasting Condition.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Sphingomod; Drug: Gilenya	Phase 1

Detailed Description:

Open-label, randomized, single dose, two-sequence, two-way crossover study, separated by 49 days washout interval from the first study drug administration.

Healthy volunteers, 18-55 years of age, selected from the Egyptian population fulfilling the selection criteria. 30 subjects will participate in the study. All dosed subject samples will be analyzed and their data will be included in the final study report.

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: An Open Label Randomized, Single Dose, Two-way Crossover Bioequivalence Study to Determine the Bioequivalence of Fingolimod From Sphingomod 0.5 mg Hard Gelatin Capsules (Hikma Pharma, Egypt) Versus Gilenya 0.5 mg Hard Capsules (Novartis Pharma AG, Basle, Switzerland) in Healthy Human Volunteers Under Fasting Condition.
• Actual Study Start Date: August 10, 2020
• Actual Primary Completion Date: September 28, 2020
• Actual Study Completion Date: October 20, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: A test; Test drug (Sphingomod ) 1 capsule contains 0.5 mg Fingolimod	Drug: Sphingomod; 1 capsule contains 0.5 mg Fingolimod; Other Name: Gilenya
Active Comparator: B reference; Reference drug (Gilenya) 1 capsule contains 0.5 mg Fingolimod	Drug: Gilenya; 1 capsule contains 0.5 mg Fingolimod

Outcome Measures

Primary Outcome Measures :

1. Cmax [ Time Frame: Up to 72 hours post dose in each treatment period ]
   Maximal measured plasma concentration

Secondary Outcome Measures :

1. Time of the maximum plasma concentration (Tmax) [ Time Frame: Up to 72 hours post dose in each treatment period ]
   The amount of time that a drug is present at the maximum concentration in serum

Eligibility Criteria

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

Criteria

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.
6. Females should be on a suitable birth control method.

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 or nursing.
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.

Contacts and Locations

Locations

Egypt

Genuine Research Center GRC

Cairo, Egypt, 11757

Sponsors and Collaborators

Genuine Research Center, Egypt

Hikma Pharmaceuticals LLC

Investigators

• Study Director: Ahmed Elshafeey, Ph.D. Pharma; Genuine Research Center

More Information

Additional Information:

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. 

Publications:

Chow SC, Wang H. On sample size calculation in bioequivalence trials. J Pharmacokinet Pharmacodyn. 2001 Apr;28(2):155-69. 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.

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.

• Responsible Party: Genuine Research Center, Egypt
• ClinicalTrials.gov Identifier: NCT04657744
• Other Study ID Numbers: GRC/1/19/786
• First Posted: December 8, 2020
• Last Update Posted: December 8, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Fingolimod Hydrochloride; Sphingosine 1 Phosphate Receptor Modulators; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs