Bioequivalence Study of of Metformin HCl From Gleptomet 50/1000 mg F.C.Tablets (EVA Pharma, Egypt) and Janumet 50/1000 mg F.C.Tablets (Merck Sharp & Dohme, The Netherlands)

Comparative, Randomized, Single Dose, Two-way Crossover Bioequivalence Study to Determine the Bioequivalence of Metformin HCl From Gleptomet 50/1000 mg F.C.Tablets (EVA Pharma for Pharmaceuticals & Medical Appliances, Egypt) and Janumet 50/1000 mg F.C.Tablets (Merck Sharp & Dohme, The Netherlands) After a Single Oral Dose Administration of Each to Healthy Adults Under Fed Conditions.

Comparative, Randomized, Single Dose, Two-way Crossover Bioequivalence Study to determine the bioequivalence of Metformin HCl From Gleptomet 50/1000 mg F.C.Tablets (EVA Pharma, Egypt) and Janumet 50/1000 mg F.C.Tablets (Merck Sharp & Dohme, The Netherlands)

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Gleptomet 50/1000(Metformin HCl & Sitagliptin); Drug: Janumet 50/1000(Metformin HCl & Sitagliptin)

Detailed Description

Healthy volunteers, 18-55 years of age, selected from the Egyptian population fulfilling the selection criteria. 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 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 Sitagliptin and/or Metformin HCl.
3. Subjects who are going to get an injection of dye or contrast agents for an x-ray procedure.
4. Subject does not agree not to consume any medication or food which may affect CYP3A4 enzyme at least one week prior to first study drug administration until donating the last sample of the study.
5. Subjects that do not agree not to consume alcohol-containing beverages and foods for 1 week before dosing and throughout the period of sample collection.
6. Heavy smokers.
7. Female subjects who were pregnant or nursing.
8. Acute infection within one week preceding first study drug administration.
9. History of drug or alcohol abuse.
10. 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.
11. Subject is on a special diet (for example subject is vegetarian).
12. 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.
13. 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.
14. Subject has a family history of severe diseases which have direct impact on the study.
15. Participation in a bioequivalence study or in a clinical study within the last 60 days, before first study drug administration.
16. Subject intends to be hospitalized within 3 months after first study drug administration.
17. 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: T test; 1 tablet contains 1000 mg Metformin HCl & 50 mg Sitagliptin orally administrated with 240 mL of a 20% glucose solution in water, followed by 60 mL of the glucose solution administered every 15 min for up to 4 hours after dosing	Drug: Gleptomet 50/1000(Metformin HCl & Sitagliptin); Test drug; Other Names: Janumet
Active Comparator: R Reference; 1 tablet contains 1000 mg Metformin HCl & 50 mg Sitagliptin orally administrated with 240 mL of a 20% glucose solution in water, followed by 60 mL of the glucose solution administered every 15 min for up to 4 hours after dosing	Drug: Janumet 50/1000(Metformin HCl & Sitagliptin); Reference drug; Other Names: Janumet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	to measure the maximal measured plasma concentration	Up to 36 hours post dose in each treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax	time of the maximum plasma concentration	Up to 36 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 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): November 29, 2022
• Primary Completion (Actual): December 13, 2022
• Study Completion (Actual): January 13, 2023

Study Registration Dates

• First Submitted: March 22, 2023
• First Submitted That Met QC Criteria: March 22, 2023
• First Posted (Actual): April 5, 2023

Study Record Updates

• Last Update Posted (Actual): April 5, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Sitagliptin Phosphate
• Other Study ID Numbers: GRC/1/21/1044

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