Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

BE Study of Metformin GSK 500mg (BA/BE 173/11)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01710527
Recruitment Status : Completed
First Posted : October 19, 2012
Results First Posted : June 2, 2017
Last Update Posted : June 2, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

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.


Condition or disease Intervention/treatment Phase
Diabetic Foot Drug: Metformin 500mg Drug: Glucophage 500mg Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: AN OPEN LABEL, BALANCED, RANDOMIZED, TWO-TREATMENT, TWO-PERIOD, TWO-SEQUENCE, CROSSOVER, SINGLE ORAL DOSE, BIOEQUIVALENCE STUDY OF 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
Actual Study Start Date : May 9, 2012
Actual Primary Completion Date : May 18, 2012
Actual Study Completion Date : May 18, 2012

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Metformin 500mg
Cross over, two treatment, two period, two sequence, cross over, single dose
Drug: Metformin 500mg
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

Drug: Glucophage 500mg
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
Cross over, two treatment, two period, two sequence, sigle dose
Drug: Metformin 500mg
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

Drug: Glucophage 500mg
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




Primary Outcome Measures :
  1. Mean Maximal Measured Plasma Concentration (Cmax) After a Single Dose [ Time Frame: 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. ]
    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.

  2. 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) [ Time Frame: 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. ]

    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.


  3. Time of the Maximum Plasma Concentration (T-max) Over Period [ Time Frame: 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. ]
    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.

  4. Terminal Half-life (T-half) Over Period [ Time Frame: 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. ]
    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.

  5. Percentage of Area Under Curve Extrapolated to Arrive at AUC0-infinity (AUC%_Extrapolated) [ Time Frame: 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. ]
    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.

  6. Apparent First-order Elimination or Terminal Rate Constant [ Time Frame: 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. ]
    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.


Secondary Outcome Measures :
  1. Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) [ Time Frame: Up to 38 days ]
    An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase >=3 x upper limit of normal (ULN), and total bilirubin >=2 x ULN or international normalized ratio >1.5.

  2. Number of Participants With Abnormal Vital Sign Results [ Time Frame: Up to 38 days ]
    Vital signs measurements (blood pressure, respiratory rate, pulse rate and oral temperature) were conducted during screening and during post study safety assessments. Vital signs measurement were also performed at each check-in and at checkout and were also recorded before dosing of study drug, between 2-3, 9-10 and 36.0 hour post-dose. Measurements were recorded in sitting position after rest of at least 5 min.

  3. Number of Participants With Abnormal Periodic Physical Examination Results [ Time Frame: Up to 38 days ]
    Brief physical examination was performed at each check-in, check-out and complete physical examination during screening and at the end of the clinical part of the study.

  4. Assessment of Subject Well-being Questionnaire [ Time Frame: Up to 38 days ]
    Subject well-being questionnaire was planned to be conducted at 1.0 and 5.0 hour post-dose. During vital sign recording each participants was planned to be asked about his well-being recorded during post study safety assessments. The data for this outcome measure was not collected during the study. Thus the results summary for this outcome measure was not produced.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

  • 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.

OR

  • 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.

Exclusion Criteria

  • 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.
  • Positive breath alcohol test result found on the day of check-in.
  • Positive urine test result for drug of abuse found on the day of check-in.
  • History of difficulty in swallowing tablet.
  • Use of any concomitant medication [including over-the-counter products, vitamins etc.] for 14 days preceding the study drug administration.
  • Use of drugs which induce or inhibit metabolizing enzymes within 30 days prior to receiving the first dose of study medication.

Other Eligibility Criteria Considerations To assess any potential impact on subject eligibility with regard to safety, the investigator must refer to the product data sheet for detailed information regarding warnings, precautions, contraindications, adverse events, and other significant data pertaining to the product being used in this study.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01710527


Sponsors and Collaborators
GlaxoSmithKline
Investigators
Layout table for investigator information
Study Director: GSK Clinical Trials GlaxoSmithKline

Publications:
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.

Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01710527    
Other Study ID Numbers: 116723
First Posted: October 19, 2012    Key Record Dates
Results First Posted: June 2, 2017
Last Update Posted: June 2, 2017
Last Verified: April 2017
Keywords provided by GlaxoSmithKline:
Healthy Volunteers
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetic Foot
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Foot Ulcer
Leg Ulcer
Skin Ulcer
Skin Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Diabetic Neuropathies
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs