GXR RM (Glucophage® Extended Release Reduced Mass) 500 Milligram (mg) Korea Bioequivalence (BE) Study

NCT04684420 | Completed Phase 1 Results

• 1 other identifier: MS200084_0028
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study was to assess bioequivalence (BE) of newly developed Glucophage® XR (GXR) reduced mass (RM) tablet (metformin hydrochloride 500 milligrams (mg) test tablet) and marketed Glucophage ® XR tablet (metformin hydrochloride 500 mg reference tablet) following single oral dose administration under fasted and fed conditions by comparing pharmacokinetics, safety and tolerability between test and reference in healthy participants.

Conditions

Healthy

Keywords

Diabetes Mellitus; Glucophage Extended Release; Bioequivalence Study

Outcome Measures

Primary Outcomes (2)

• Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Metformin

  Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.

  Part 1 (fasted): Pre-dose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24 and 32 hours post dose. Part 2 (fed): Pre-dose 1, 2, 3, 4, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 24 and 32 hours post dose

• Maximum Observed Plasma Concentration (Cmax) of Metformin

  Cmax was obtained directly from the concentration versus time curve.

  Part 1 (fasted): Pre-dose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24 and 32 hours post dose. Part 2 (fed): Pre-dose 1, 2, 3, 4, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 24 and 32 hours post dose

Secondary Outcomes (10)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs

  From Day 1 up to 3 weeks

• Number of Participants Taking Concomitant Medications

  From Day 1 up to 3 weeks

• Number of Participants With Clinically Significant Change From Baseline in Laboratory Values

  From Day1 (baseline) up to 3 weeks

• Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings

  From Day 1 (baseline) up to 3 weeks

• Number of Participants With Clinically Significant Change From Baseline in Vital Signs

  From Day 1 (baseline) up to 3 weeks

Study Arms (4)

First Reference GXR (Fasting), Then Test GXR RM (Fasting)

EXPERIMENTAL

Participants received a single oral dose of 500 milligram (mg) of reference GXR (Glucophage® Extended Release) tablet on Day 1 in treatment period 1 followed by single oral dose of 500 mg test GXR RM (Reduced Mass) tablet on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.

Drug: Glucophage® XR RM Test; Drug: Glucophage® XR Reference

First Test GXR RM (Fasting), Then Reference GXR (Fasting)

EXPERIMENTAL

Participants received a single oral dose of 500 milligrams (mg) of test GXR RM tablet on Day 1 in treatment period 1 followed by single oral dose of 500 mg of reference GXR tablet on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.

Drug: Glucophage® XR RM Test; Drug: Glucophage® XR Reference

First Reference GXR (Fed), Then Test GXR RM (Fed)

EXPERIMENTAL

Participants received a single oral dose of 500 milligrams (mg) of reference GXR tablet on Day 1 in treatment period 1 followed by single oral dose of 500 mg of test GXR RM tablet on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.

Drug: Glucophage® XR RM Test; Drug: Glucophage® XR Reference

First Test GXR RM (Fed), Then Reference GXR (Fed)

EXPERIMENTAL

Participants received a single oral dose of 500 milligrams (mg) of test GXR RM tablet on Day 1 in treatment period 1 followed by single oral dose of 500 mg of reference GXR tablet on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.

Drug: Glucophage® XR RM Test; Drug: Glucophage® XR Reference

Interventions

Glucophage® XR RM Test DRUG

Participants received a single oral dose of 500 mg of test Glucophage® XR RM tablet under fasting or fed conditions.

Also known as: Metformin hydrochloride

First Reference GXR (Fasting), Then Test GXR RM (Fasting); First Reference GXR (Fed), Then Test GXR RM (Fed); First Test GXR RM (Fasting), Then Reference GXR (Fasting); First Test GXR RM (Fed), Then Reference GXR (Fed)

Glucophage® XR Reference DRUG

Participants received a single oral dose of 500 mg of reference Glucophage® XR tablet under fasting or fed conditions.

Also known as: Metformin hydrochloride

First Reference GXR (Fasting), Then Test GXR RM (Fasting); First Reference GXR (Fed), Then Test GXR RM (Fed); First Test GXR RM (Fasting), Then Reference GXR (Fasting); First Test GXR RM (Fed), Then Reference GXR (Fed)

Eligibility Criteria

• Age: 19 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• All values for hematology and biochemistry tests of blood and urinalysis (especially Estimated Glomerular Filtration Rate \[eGFR\] greater than \[\>\] 80 milliliters per minute per 1.73 square meter \[80 ml/min/1.73 m\^2\] and normal Creatinine) within the normal range or showing no clinically relevant deviation as judged by the Investigator
• Are not having congenital or chronic diseases, nor pathological symptoms based on the screening
• Have no history of gastrointestinal resection that may affect drug absorption
• Have no history of psychiatric disorder within 5 years prior to screening
• Vital signs (body temperature \[tympanic\], blood pressure \[BP\], and pulse rate in sitting position) within the normal range or showing no clinically relevant deviation as judged by the Investigator
• Electrocardiogram recording (12-lead) without signs of clinically relevant pathology in particular QTc (Bazett) less than or equal to \[\<=\] 450 millisecond (ms)
• Non-smoker (that is \[i.e.\] zero cigarettes, pipes, cigars or others) at least three months before study entry
• Negative screen for Hepatitis B surface antigen (HBsAg) and Hepatitis B Virus antibody (anti-HBc), Hepatitis C Virus antibody (anti-HCV) and Human Immunodeficiency Virus antibodies (anti-HIV 1 and 2) and Rapid Plasma Reagin Antibody (RPR Ab)
• Have a body weight within the range 55 to 95 kilograms (kg) and a Body Mass Index (BMI) within the range 18.5 to 29.9 kilograms per square meter (kg/m\^2) (inclusive)

You may not qualify if:

• Participants determined ineligible to participate in this study at the discretion of the Principal Investigator (or delegated investigators)
• Hypersensitivity to venous puncture
• Known hypersensitivity to ingredients of Study Interventions or Biguanides, or having other clinically relevant hypersensitivities
• Type I diabetes mellitus, lactic acidosis, acute or chronic metabolic acidosis including diabetic ketoacidosis, with or without coma; diabetic pre-coma, pre-diabetes
• Participants with renal impairment (eGFR \< 80 ml/min/1.73m\^2) - calculations according to Modification of Diet in Renal Disease (MDRD) formula). Participants presenting with acute conditions with the potential to alter renal function such as dehydration, severe infection, cardiovascular collapse (shock), acute myocardial infraction, and septicemia
• Participants with acute and unstable heart failure
• Participants with severe infection or severe traumatic general disorder
• Participants who are scheduled to undergo surgical procedures
• Participants with malnutrition, inanition, pituitary dysfunction or adrenal function failure
• Participants with hepatic dysfunction, acute or chronic disease which may cause tissue hypoxia such as respiratory failure, acute myocardial infarction, shock and gastrointestinal (GI) disorder such as excessive alcohol intake, hydration, diarrhea, vomiting etc.
• Participants undergoing intravascular administration of iodinated contrast materials in radio diagnostic examinations (for example, intravenous urogram, intravenous cholangiography, angiography, and computed tomography (CT) scans with intravascular contrast materials etc.)
• Participants who took drugs that significantly induce (e.g., barbiturate) or inhibit drug metabolism enzymes, and those drugs that may alter metformin pharmacokinetic (pK), most importantly organic cation transporter 1/2 \[OCT1/2\] inhibitors and inducers, within 30 days prior to screening
• Use of a concomitant drug. However, any medications that are considered necessary for participant's welfare and will not interfere with the trial medication may be given at the discretion of the investigator
• Use of any medication that may affect the outcome of the study within 10 days prior to screening and during study conduct
• Participation in another bioequivalence or other clinical studies where the last administration of previous study medication was within 6 months, before the first drug administration in this study

Sponsors & Collaborators

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

Study Sites (1)

Clinical Trials Center, Chungnam National University Hospital

Daejeon, 35015, South Korea

Location

Related Links

• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contact

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Metformin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49 6151 72 5200

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2020
• First Posted: December 24, 2020
• Study Start: December 22, 2020
• Primary Completion: March 11, 2022
• Study Completion: March 11, 2022
• Last Updated: December 29, 2023
• Results First Posted: December 29, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)