Glucophage Immediate Release (GIR) China Bioequivalence Study

NCT03393208 | Completed Phase 1 Results

• 1 other identifier: MS200084_0009
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The study will assess the bioequivalence between single doses of glucophage immediate release (GIR) test tablets and GIR reference tablets under fed and fasted state in healthy subjects.

Conditions

Healthy

Keywords

Diabetes Mellitus; Glucophage Immediate Release (GIR); Bioequivalence Study

Outcome Measures

Primary Outcomes (2)

• Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Metformin (GIR Tablet Active Ingredient)

  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.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

• Maximum Observed Plasma Concentration (Cmax) of Metformin (GIR Tablet Active Ingredient)

  Pharmacokinetic (PK) parameter Cmax was obtained directly from the concentration versus time curve.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

Secondary Outcomes (10)

• Time to Reach Maximum Plasma Concentration of Metformin (GIR Tablet Active Ingredient)

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

• Apparent Terminal Half-Life (t1/2) of Metformin (GIR Tablet Active Ingredient)

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

• Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUCinf) of Metformin (GIR Tablet Active Ingredient)

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

• Area Under the Plasma Concentration-Time Curve From Time Tlast Extrapolated to Infinity (AUCextra) of Metformin (GIR Tablet Active Ingredient)

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

• Elimination Rate Constant (λz) of Metformin (GIR Tablet Active Ingredient)

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

Study Arms (4)

First Test GIR (Fasting), Then Reference GIR (Fasting)

EXPERIMENTAL

Participants received a single oral dose of 500 milligram (mg) of test Glucophage Immediate Release (GIR) tablet Sino-American Shanghai Squibb (SASS)/China) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg reference GIR (Merck Santé in Semoy (MSS)/France) on Day 8 in treatment period 2 under fasting condition. There was a wash-out period of 7 days between each treatment period.

Drug: Test GIR; Drug: Reference GIR

First Reference GIR (Fasting), Then Test GIR (Fasting)

EXPERIMENTAL

Participants received a single oral dose of 500 mg of reference GIR tablet (MSS/France) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg test GIR (SASS/China) on Day 8 in treatment period 2 under fasting condition. There was a wash-out period of 7 days between each treatment period.

Drug: Test GIR; Drug: Reference GIR

First Test GIR (Fed), Then Reference GIR (Fed)

EXPERIMENTAL

Participants received a single oral dose of 500 mg of test GIR tablet (SASS/ China) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg reference GIR (MSS/France) on Day 8 in treatment period 2 under fed condition. There was a wash-out period of 7 days between each treatment period.

Drug: Test GIR; Drug: Reference GIR

First Reference GIR (Fed), Then Test GIR (Fed)

EXPERIMENTAL

Participants received a single oral dose of 500 mg of reference GIR tablet (MSS/ France) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg test GIR (SASS/China) on Day 8 in treatment period 2 under fed condition. There was a wash-out period of 7 days between each treatment period.

Drug: Test GIR; Drug: Reference GIR

Interventions

Test GIR DRUG

Participants received 500 milligrams (mg) test GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).

Also known as: Metformin

First Reference GIR (Fasting), Then Test GIR (Fasting); First Reference GIR (Fed), Then Test GIR (Fed); First Test GIR (Fasting), Then Reference GIR (Fasting); First Test GIR (Fed), Then Reference GIR (Fed)

Reference GIR DRUG

Participants received 500 mg reference GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).

Also known as: Metformin

First Reference GIR (Fasting), Then Test GIR (Fasting); First Reference GIR (Fed), Then Test GIR (Fed); First Test GIR (Fasting), Then Reference GIR (Fasting); First Test GIR (Fed), Then Reference GIR (Fed)

Eligibility Criteria

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

You may qualify if:

• Participants had given written informed consent before any trial-related activities
• Chinese male and female participants (at least 1/4 of each gender per trial group)
• Aged between 18 and 55 years, inclusive
• Weighed: 50 to 80 kilogram (kg); Body mass index (BMI): 18 to 30 kg per meter square
• Nonsmoker since at least 3 months
• Good physical and mental health status, determined on the basis of the medical history and a physical examination
• All values for biochemistry and hematology tests of blood and urine within the normal range or showied no clinically relevant deviation as judged by the Investigator
• Electrocardiogram recording (12-lead ECG) without signs of clinically relevant pathology was judged by the Investigator
• Vital signs (blood pressure, pulse, body temperature, and respiration) in sitting position within the normal range or showing no clinically relevant deviation was judged by the Investigator
• All women of childbearing potential (WOCBP) who were not nursing, were not pregnant, and were using highly effective methods of birth control
• Negative screen for alcohol and drugs of abuse (cannabis, benzodiazepines, barbiturates, opiates, cocaine, and methyl amphetamine) were screened at and on admission
• Negative screen for hepatitis A virus (HAV) antibodies, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, human immunodeficiency virus (HIV) antibodies, and Treponema pallidum (TP) antibodies

You may not qualify if:

• Participation in a clinical trial within 90 days prior to first drug administration
• Blood donation (equal or more than 500 milliliter \[mL\]) or significant blood loss within 90 days prior to first drug administration
• 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 of the participant in the trial or that could interfere with the trial objectives, conducted or evaluated
• History of surgery of the gastrointestinal tract which could influence the gastrointestinal absorption and/or motility according to the Investigator's opinion
• History or presence of relevant liver diseases or hepatic dysfunction Allergy: ascertained or presumptive hypersensitivity to the active drug substance and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the Investigator considered affectted the outcome of the trial
• Receipt of any prescription or nonprescription medication within 2 weeks before the first IMP administration, including multivitamins and herbal products (example, St John's Wort, or traditional Chinese medicines), except paracetamol
• Renal failure or renal dysfunction (creatinine clearance \< 80 mL/minute) as assessed by using the estimated measure with the Modification of Diet in Renal Disease (MDRD) equation
• Known lack of participant compliance or inability to communicate or cooperate with the Investigator (example, language problem and poor mental status)
• Nonacceptance of trial high-fat breakfast (example, vegetarians, vegans, and participants followed special diets)
• Consumption of large quantities of methyl xanthine-containing beverages (\> 5 cups of coffee/day or equivalent)
• Consumption of grapefruit, cranberry or juices of these fruits, from 14 days prior to drug administration until collection of the last pharmacokinetic sample in Period 2
• Any contraindication to Glucophage
• Abnormal and clinically significant chest X-ray finding at screening

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

Xuanwu Hospital

Beijing, 100053, China

Location

Related Publications (1)

• Hu C, Gao D, Li D, Zhou D, Zhang L. Chinese- and French-Manufactured Immediate-Release Glucophage(R) Bioequivalence: A Randomized, Open-Label, Crossover Study. Drugs R D. 2022 Dec;22(4):301-309. doi: 10.1007/s40268-022-00405-3. Epub 2022 Oct 20.

  PMID: 36264446 DERIVED

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 KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  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 22, 2017
• First Posted: January 8, 2018
• Study Start: January 10, 2018
• Primary Completion: January 29, 2018
• Study Completion: January 29, 2018
• Last Updated: July 15, 2019
• Results First Posted: July 15, 2019

Record last verified: 2019-04

Locations

CN (1)