BE Study of Metformin GSK 500mg

NCT01710527 | Completed Phase 2 Results

• 1 other identifier: 116723
• Study Type: interventional
• Target: 32
• Locations: 0 countries
• Sites: N/A

Brief Summary

A randomized, balanced, open label, crossover, two period, two treatment, two sequence, single dose, oral bioequivalence study under fasting condition. It is a pivotal study. To demonstrate the bioequivalence of Metformin 500 mg tablets manufactured by Savipharm J.S.C, Vietnam and Glucophage® 500 mg tablets of MERCK SANTE in healthy adult human male subjects under fasting condition and to monitor the safety of the study subjects.

Conditions

Diabetic Foot

Keywords

Healthy Volunteers

Outcome Measures

Primary Outcomes (6)

• Mean Maximal Measured Plasma Concentration (Cmax) After a Single Dose

  Plasma samples for pharmacokinetic (PK) analysis were drawn at indicated time points of each treatment period. Cmax was defined as maximal measured plasma concentration over the time span specified.

  Pre- dose (0.0 hour), post-dose at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 36.0 hour in each period.

• Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) and Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-infinity)

  Plasma samples for PK analysis were drawn at indicated time points of each treatment period. AUC0-t was calculated by the linear trapezoidal rule from measured data points from time of administration until the time of last quantifiable concentration. AUC0- infinity was estimated by linear trapezoidal rule and was sum of the AUC0-t and extrapolated to infinity by dividing the estimated last measurable plasma concentration by elimination rate constant. The AUC0- infinity was the sum of the estimated and extrapolated parts.

  Pre- dose (0.0 hour), post-dose at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 36.0 hour in each period.

• Time of the Maximum Plasma Concentration (T-max) Over Period

  Plasma samples for PK analysis were drawn at indicated time points of each treatment period. If the maximum value occurs at more than one point T-max was defined as the first time point with this value.

  Pre- dose (0.0 hour), post-dose at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 36.0 hour in each period.

• Terminal Half-life (T-half) Over Period

  Plasma samples for PK analysis were drawn at indicated time points of each treatment period. The elimination or terminal half-life was calculated by dividing 0.693 (natural logarithm of 2) with elimination rate constant obtained as semi logarithmic plot of the plasma concentration versus time.

  Pre- dose (0.0 hour), post-dose at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 36.0 hour in each period.

• Percentage of Area Under Curve Extrapolated to Arrive at AUC0-infinity (AUC%_Extrapolated)

  Plasma samples for PK analysis were drawn at indicated time points of each treatment period. AUC%\_Extrapolated was obtained by subtracting AUC0-t from AUC0-infinity divided by AUC0-infinity and multiplied by 100.

  Pre- dose (0.0 hour), post-dose at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 36.0 hour in each period.

• Apparent First-order Elimination or Terminal Rate Constant

  Plasma samples for PK analysis were drawn at indicated time points of each treatment period. The apparent first-order elimination or terminal rate constant was calculated from a semi logarithmic plot of the plasma concentration versus time. The parameter was calculated by linear least-square regression analysis using the last three (or more) non-zero plasma concentrations.

  Pre- dose (0.0 hour), post-dose at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 36.0 hour in each period.

Secondary Outcomes (4)

• Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)

  Up to 38 days

• Number of Participants With Abnormal Vital Sign Results

  Up to 38 days

• Number of Participants With Abnormal Periodic Physical Examination Results

  Up to 38 days

• Assessment of Subject Well-being Questionnaire

  Up to 38 days

Study Arms (2)

Metformin 500mg

OTHER

Cross over, two treatment, two period, two sequence, cross over, single dose

Drug: Metformin 500mg; Drug: Glucophage 500mg

Glucophage 500mg

OTHER

Cross over, two treatment, two period, two sequence, sigle dose

Drug: Metformin 500mg; Drug: Glucophage 500mg

Interventions

Metformin 500mg DRUG

EVALUATE BIOEQUIVALENCE BETWEEN METFORMIN 500 MG TABLETS MANUFACTURED BY SAVIPHARM J.S.C, VIETNAM AND GLUCOPHAGE® 500 MG TABLETS MANUFACTURED BY MERCK SANTE S.A.S.2, RUE DU PRESSOIR VERT-45400 SEMOY-FRANCE AND BE REGISTERED IN VIETNAM IN HEALTHY, ADULT, HUMAN MALE SUBJECTS UNDER FASTING CONDITION

Glucophage 500mg; Metformin 500mg

Glucophage 500mg DRUG

EVALUATE BIOEQUIVALENCE BETWEEN METFORMIN 500 MG TABLETS MANUFACTURED BY SAVIPHARM J.S.C, VIETNAM AND GLUCOPHAGE® 500 MG TABLETS MANUFACTURED BY MERCK SANTE S.A.S.2, RUE DU PRESSOIR VERT-45400 SEMOY-FRANCE AND BE REGISTERED IN VIETNAM IN HEALTHY, ADULT, HUMAN MALE SUBJECTS UNDER FASTING CONDITION

Glucophage 500mg; Metformin 500mg

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult male human subjects within the age range of 18 to 45 years inclusive.
• Weight not less than 50 kg.
• Normal BMI \[18.5 to 24.99 kg/m2 inclusive\].
• Willingness and capability to provide written informed consent to participate in the study.
• Free of significant diseases or clinically significant abnormal findings based on medical history, physical examination, laboratory evaluations, 12-lead ECG, Chest X-ray \[PA view\].
• Absence of disease markers of HIV 1 and 2, Hepatitis B and C and Syphilis.
• AST, ALT, alkaline phosphatase and bilirubin \</=1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• ECG normal for morphology and measurements. QTcB or QTcF \< 450 msec or QTc \< 480 msec in subjects with Bundle Branch Block, based on an average from three ECGs obtained over a brief recording period.
• Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed below. This criterion must be followed from the time of the first dose of study medication until one week of last dose administration.
• Condom plus partner use of a highly effective contraceptive such as occlusive cap (diaphragm or cervical/vault cap) plus spermicidal agent (foam/gel/film/cream/suppository), oral contraceptive, injectable progesterone, implant of etonogestrel or levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, or intrauterine device.
• Abstinence, defined as sexual inactivity consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

You may not qualify if:

• History or presence of significant: Cardiovascular, pulmonary, hepatic, renal, hematological, gastro-intestinal, endocrine, immunologic, dermatologic, neurological, psychiatric disease.
• History or presence of significant:
• Alcohol dependence, alcohol abuse during past one year.
• Drug abuse \[Marijuana \[THC\], Cocaine, Morphine, Benzodiazepines, Barbiturates and Amphetamine\] for the last 6 months.
• Smoking of more than 5 cigarettes per day or consumption of other forms of tobacco containing products.
• Asthma, urticaria or other allergic type reactions after taking aspirin or any other drug.
• Ulceration or history of gastric and / or duodenal ulcer.
• Jaundice in the past 6 months.
• Bleeding disorder.
• Allergy to the test drug or any drug chemically similar to the drug or to the excipients of the products under investigation.
• Donation of 500 mL or more blood within 8 weeks prior to receiving the first dose of study drug.
• Subjects who have participated in another clinical study in the past 3 months prior to commencement of this study.
• Any difficulty in accessibility of forearm veins for cannulation or blood sampling.
• Refusal to abstain from food for at least 10 h prior to drug administration and for at least 4 h post dose in each period.
• Refusal to abstain from fluid for at least 1 h prior to and 1 h post each dose except 20 % glucose solution given after dosing.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Related Publications (1)

• GSK has concluded that it is not feasible to publish this study in a peer-reviewed scientific journal because the nature of the study is unlikely to be of interest to a journal. GSK is providing a results summary with a conclusion.

  BACKGROUND

MeSH Terms

Conditions

Diabetic Foot

Interventions

Metformin

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2012
• First Posted: October 19, 2012
• Study Start: May 9, 2012
• Primary Completion: May 18, 2012
• Study Completion: May 18, 2012
• Last Updated: June 2, 2017
• Results First Posted: June 2, 2017

Record last verified: 2017-04