Glucophage Immediate Release (GIR) China Bioequivalence Study

NCT ID: NCT03393208

Last Updated: 2019-07-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-10
• Study Completion Date: 2018-01-29

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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

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.

Group Type: EXPERIMENTAL

Test GIR

Intervention Type: 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).

Reference GIR

Intervention Type: 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).

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

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.

Group Type: EXPERIMENTAL

Test GIR

Intervention Type: 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).

Reference GIR

Intervention Type: 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).

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

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.

Group Type: EXPERIMENTAL

Test GIR

Intervention Type: 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).

Reference GIR

Intervention Type: 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).

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

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.

Group Type: EXPERIMENTAL

Test GIR

Intervention Type: 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).

Reference GIR

Intervention Type: 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).

Interventions

Test GIR

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).

Intervention Type: DRUG

Reference GIR

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

Intervention Type: DRUG

Other Intervention Names

Metformin; Metformin

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

Xuanwu Hospital

Beijing, , China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 36264446 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

MS200084_0009

Identifier Type: -

Identifier Source: org_study_id