GXR RM China BE Study (Darmstadt - Jiangsu)

A Randomized, Open-label, 2-Way-Crossover Study Assessing the Bioequivalence Between Single Doses of 500 mg Glucophage® XR RM Tablets (Merck/China Jiangsu-Manufactured) and 500 mg Glucophage® XR RM Tablets (Merck/Germany Darmstadt-Manufactured) Under Fed and Fasted State in Healthy Participants

The purpose of this study is to assess Bioequivalence (BE), pharmacokinetics (PK), safety and tolerability following single oral dose administrations between a Glucophage Extended Release, Reduced Mass (Glucophage XR RM) manufactured in Merck Jiangsu China (test product) and that manufactured in Merck Darmstadt Germany (reference product) administered under fasted and fed conditions.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Test Glucophage® XR; Drug: Reference Glucophage® XR

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Darmstadt, Germany
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participants who are overtly healthy as determined by medical evaluation, including medical history, ECG recording and physical examination judged by investigator.
• Participants with a body weight within 50 to 90 kg (kilogram) and BMI (body mass index) within the range 19 to 26 kg/m2 (kilogram per meter square).
• Participants with all values for biochemistry and hematology tests of blood and urine within the normal range or showing no clinically relevant deviation as judged by the Investigator.
• Other protocol defined inclusion criteria could apply.

Exclusion Criteria:

• Participants with any surgical or medical condition, including findings in the medical history or in the pretrial assessments, or any other significant disease, that in the opinion of the Investigator, constitutes a risk or a contraindication for the participation in the study or that could interfere with the study objectives, conduct or evaluation.
• Participants with history or presence of relevant liver diseases or hepatic or renal dysfunction.
• Participants with history of surgery of the gastrointestinal tract which could influence the gastrointestinal absorption and/or motility according to the Investigator's opinion.
• Participation in a clinical study within 90 days prior to first drug administration.
• Non-acceptance of study high-fat breakfast.
• Other protocol defined exclusion criteria could apply .

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: First Test GXR RM (Fasted), Then Reference GXR RM (Fasted); Participants will receive a single dose of Test Glucophage Extended Release Reduced Mass (GXR RM) tablet on Day 1 in treatment period 1 followed by a single dose of Reference GXR RM tablet on Day 8 in treatment period 2 under fasted condition. There will be separate washout period of 7 days between each treatment period.	Drug: Test Glucophage® XR; Participants will receive single oral dose of Test GXR RM tablet under fasted or fed conditions.; Other Names: Metformin hydrochloride; Drug: Reference Glucophage® XR; Participants will receive single oral dose of Reference GXR RM tablet under fasted or fed conditions.; Other Names: Metformin hydrochloride
Experimental: First Reference GXR RM (Fasted), Then Test GXR RM (Fasted); Participants will receive a single dose of Reference GXR RM tablet on Day 1 in treatment period 1 followed by a single dose of Test GXR RM tablet on Day 8 in treatment period 2 under fasted condition. There will be separate washout period of 7 days between each treatment period.	Drug: Test Glucophage® XR; Participants will receive single oral dose of Test GXR RM tablet under fasted or fed conditions.; Other Names: Metformin hydrochloride; Drug: Reference Glucophage® XR; Participants will receive single oral dose of Reference GXR RM tablet under fasted or fed conditions.; Other Names: Metformin hydrochloride
Experimental: First Test GXR RM (Fed), Then Reference GXR RM (Fed); Participants will receive a single dose of Test GXR RM tablet on Day 1 in treatment period 1 followed by a single dose of Reference GXR RM tablet on Day 8 in treatment period 2 under fed condition. There will be separate washout period of 7 days between each treatment period.	Drug: Test Glucophage® XR; Participants will receive single oral dose of Test GXR RM tablet under fasted or fed conditions.; Other Names: Metformin hydrochloride; Drug: Reference Glucophage® XR; Participants will receive single oral dose of Reference GXR RM tablet under fasted or fed conditions.; Other Names: Metformin hydrochloride
Experimental: First Reference GXR RM (Fed), Then Test GXR RM (Fed); Participants will receive a single dose of Reference GXR RM tablet on Day 1 in treatment period 1 followed by a single dose of Test GXR RM tablet on Day 8 in treatment period 2 under fed condition. There will be separate washout period of 7 days between each treatment period.	Drug: Test Glucophage® XR; Participants will receive single oral dose of Test GXR RM tablet under fasted or fed conditions.; Other Names: Metformin hydrochloride; Drug: Reference Glucophage® XR; Participants will receive single oral dose of Reference GXR RM tablet under fasted or fed conditions.; Other Names: Metformin hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Metformin	Pre-dose up to 48 hours post-dose on Day 1 and Day 8
Maximum Observed Plasma Concentration (Cmax) of Metformin	Pre-dose up to 48 hours post-dose on Day 1 and Day 8

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic Plasma Concentrations of Metformin	Pre-dose up to 48 hours post-dose on Day 1 and Day 8
Number of Participants with Treatment-Emergent Adverse Events (AEs)	Baseline up to Day 10
Number of Participants with Abnormal Laboratory Variables, Vital Signs and 12-Lead Electrocardiogram (ECG) Measurements and Physical Examination	Baseline up to Day 10

Collaborators and Investigators

• Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

Helpful Links

• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2022
• Primary Completion (Actual): January 3, 2023
• Study Completion (Actual): January 3, 2023

Study Registration Dates

• First Submitted: July 14, 2022
• First Submitted That Met QC Criteria: July 14, 2022
• First Posted (Actual): July 18, 2022

Study Record Updates

• Last Update Posted (Actual): April 14, 2023
• Last Update Submitted That Met QC Criteria: April 13, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Bioequivalence; Glucophage® XR RM
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: MS200084_0030

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website http://bit.ly/IPD21

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No