ClinicalTrials.gov
ClinicalTrials.gov Menu

OXEMET™ 1000 mg Coated Tablets (Metformin Hydrochloride) Bioequivalence Study. OXEMET (TM) is a Trademark of the GlaxoSmithKline Group of Companies. GLAFORNIL(TM) is a Trademark of Merck.

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: NCT01842620
Recruitment Status : Completed
First Posted : April 29, 2013
Results First Posted : December 22, 2017
Last Update Posted : December 22, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Condition Diabetes Mellitus, Type 2
Intervention Drug: Metformin
Enrollment 25
Recruitment Details This study was conducted from 13 Mar 2013 to 04 May 2013 at single center in Argentina.
Pre-assignment Details A total of 25 participants were enrolled in the study; however, one participant withdrew from the study before completing the two study periods. The remaining 24 participants were considered for the pharmacokinetic (PK) analyses.
Arm/Group Title OXEMET Then GLAFORNIL GLAFORNIL Then OXEMET
Hide Arm/Group Description Eligible participants received single oral metformin (OXEMET) 1000 milligrams (mg) for one day in Treatment period 1 and was followed by 7 days washout period. Participants then received single oral metformin (GLAFORNIL) 500 mg twice daily (BID) for one day in Treatment period 2, followed by 7 days follow-up period. The two treatment periods were separated by a washout period of 7 days and participants received the study drugs in a randomized manner. Eligible participants received single oral metformin (GLAFORNIL) 500 mg BID for one day in Treatment period 1 and was followed by 7 days washout period. Participants then received single oral metformin (OXEMET) 1000 mg for one day in Treatment period 2, followed by 7 days follow-up period. The two treatment periods were separated by a washout period of 7 days and participants received the study drugs in a randomized manner.
Period Title: Period 1
Started 13 12
Completed 12 12
Not Completed 1 0
Reason Not Completed
Withdrawal by Subject             1             0
Period Title: Washout Period
Started 12 12
Completed 12 12
Not Completed 0 0
Period Title: Period 2
Started 12 12
Completed 12 12
Not Completed 0 0
Arm/Group Title Total Population
Hide Arm/Group Description Eligible participants received single oral metformin (OXEMET) 1000 mg for one day and single oral metformin (GLAFORNIL) 500 mg BID for one day in each of the two treatment periods in a randomized manner. Participants had a washout period of 7 days between two treatment periods and were followed up to 7 days after the last dose of the study drug
Overall Number of Baseline Participants 25
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 25 participants
27.8  (7.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
Female
10
  40.0%
Male
15
  60.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
Hispanic or Latino
25
 100.0%
Not Hispanic or Latino
0
   0.0%
Unknown or Not Reported
0
   0.0%
1.Primary Outcome
Title Geometric Means of Area Under Plasma Concentration Time Curve of the Test Drug (Oxemet) to the Reference Drug (Glafornail) From Time Zero to the Time of Last Quantifiable Concentration of 36 Hours (h)
Hide Description Area under plasma concentration-time curve of metformin was quantifiable from time 0 to 36 h. The parameter was calculated by non-compartmental methods with WinNonlin Version 6.02. The calculations were based on the actual sampling times recorded during the study. Period wise outcome data has been presented; however, the statistical analysis has been presented for overall period.
Time Frame From 0 to 36 hours (h)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK parameters [PKP] population included all the participants who underwent plasma PK sampling and had evaluable area under curve assay results.
Arm/Group Title OXEMET 1000 mg Once Daily GLAFORNIL 1000 mg BID
Hide Arm/Group Description:
Eligible participants received single oral metformin (OXEMET) 1000 mg for one day in each of the two treatment periods in a randomized manner. Participants had a washout period of 7 days between two treatment periods and were followed up to 7 days after the last dose of the study drug.
Eligible participants received single oral metformin (GLAFORNIL) 500 mg BID for one day each in each of the two treatment periods in a randomized manner. Participants had a washout period of 7 days between two treatment periods and were followed up to 7 days after the last dose of the study drug.
Overall Number of Participants Analyzed 24 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram* h/millilitre (ng*h/mL)
Period 1
12348
(27%)
12727
(22%)
Period 2
13470
(26%)
13069
(24%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OXEMET 1000 mg Once Daily, GLAFORNIL 1000 mg BID
Comments Overall period
Type of Statistical Test Equivalence
Comments Geometric means ratio for AUC (0-t) of test drug (Oxemet) to be entirely fallen within range of 0.80 to 1.25 of that of reference drug (Glafornil).
Method of Estimation Estimation Parameter (Ratio of AUC0-36)*100
Estimated Value 100
Confidence Interval (2-Sided) 90%
92.62 to 107.98
Estimation Comments Ratio of AUC0-36= (AUC0-36 of Test)/ AUC 0-36 Reference)
2.Primary Outcome
Title Geometric Means for Area Under Plasma Concentration Time Curve of the Study Drug (Oxemet) to the Reference Drug (Glafornail) Between Time Zero to Infinity (Inf) Over Period
Hide Description Area under plasma concentration-time curve of metformin from time 0 to inf was calculated by non-compartmental methods with WinNonlin Version 6.02. The calculations were based on the actual sampling times recorded during the study. Period wise outcome data has been presented; however, the statistical analysis has been presented for overall period.
Time Frame From 0 to 36 h
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKP population included all the participants who underwent plasma PK sampling and had evaluable area under curve assay results
Arm/Group Title OXEMET 1000 mg Once Daily GLAFORNIL 1000 mg BID
Hide Arm/Group Description:
Eligible participants received single oral metformin (OXEMET) 1000 mg for one day in each of the two treatment periods in a randomized manner. Participants had a washout period of 7 days between two treatment periods and were followed up to 7 days after the last dose of the study drug.
Eligible participants received single oral metformin (GLAFORNIL) 500 mg BID for one day each in each of the two treatment periods in a randomized manner. Participants had a washout period of 7 days between two treatment periods and were followed up to 7 days after the last dose of the study drug.
Overall Number of Participants Analyzed 24 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
Period 1
12636
(26%)
13171
(21%)
Period 2
13902
(25%)
13604
(22%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OXEMET 1000 mg Once Daily, GLAFORNIL 1000 mg BID
Comments For overall period
Type of Statistical Test Equivalence
Comments Geometric means ratio for AUC(0-inf) of test drug (Oxemet) to be entirely fallen within range of 0.80 to 1.25 of that of reference drug (Glafornil).
Method of Estimation Estimation Parameter (Ratio of AUC0-inf)*100
Estimated Value 99.02
Confidence Interval (2-Sided) 90%
92.26 to 106.27
Estimation Comments Ratio of AUC0-inf= (AUC0-inf of Test) / (AUC 0-inf of Reference)
3.Primary Outcome
Title Geometric Means for Maximum Plasma Concentration of the Study Drug (Oxemet) to the Reference Drug (Glafornail) From 0 to 36 h
Hide Description Cmax is maximum plasma concentration of metformin. Plasma concentration-time curve of metformin from time 0 to 36 h was calculated by non-compartmental methods with WinNonlin Version 6.02. The calculations were based on the actual sampling times recorded during the study. Period wise data has been presented; however, the statistical analysis has been presented for overall period.
Time Frame From 0 to 36 h
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKP population
Arm/Group Title OXEMET 1000 mg Once Daily GLAFORNIL 1000 mg BID
Hide Arm/Group Description:
Eligible participants received single oral metformin (OXEMET) 1000 mg for one day in each of the two treatment periods in a randomized manner. Participants had a washout period of 7 days between two treatment periods and were followed up to 7 days after the last dose of the study drug.
Eligible participants received single oral metformin (GLAFORNIL) 500 mg BID for one day each in each of the two treatment periods in a randomized manner. Participants had a washout period of 7 days between two treatment periods and were followed up to 7 days after the last dose of the study drug.
Overall Number of Participants Analyzed 24 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Period 1
2031.5
(32%)
2097.8
(23%)
Period 2
2124.5
(28%)
2127.4
(25%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OXEMET 1000 mg Once Daily, GLAFORNIL 1000 mg BID
Comments Overall period
Type of Statistical Test Equivalence
Comments Geometric means ratio for Cmax of test drug (Oxemet) to be entirely fallen within range of 0.80 to 1.25 of that of reference drug (Glafornil).
Method of Estimation Estimation Parameter (Ratio of Cmax)*100
Estimated Value 98.34
Confidence Interval (2-Sided) 90%
88.54 to 109.22
Estimation Comments Ratio of Cmax= (Cmax of Test) / (Cmax of Reference)
4.Secondary Outcome
Title The Elimination Constant (Kel) of the Study Drug (Oxemet) and the Reference Drug (Glafornail) From 0 to 36 h
Hide Description The elimination constant (kel) of Metformin was analyzed for each participant, both for Test and Reference products. The calculations were based on the actual sampling times recorded during the study.
Time Frame From 0 to 36 h
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKP population
Arm/Group Title OXEMET 1000 mg Once Daily GLAFORNIL 1000 mg BID
Hide Arm/Group Description:
Eligible participants received single oral metformin (OXEMET) 1000 mg for one day in each of the two treatment periods in a randomized manner. Participants had a washout period of 7 days between two treatment periods and were followed up to 7 days after the last dose of the study drug.
Eligible participants received single oral metformin (GLAFORNIL) 500 mg BID for one day each in each of the two treatment periods in a randomized manner. Participants had a washout period of 7 days between two treatment periods and were followed up to 7 days after the last dose of the study drug.
Overall Number of Participants Analyzed 24 24
Median (Full Range)
Unit of Measure: Per hour
Treatment period 1
0.0981
(0.0357 to 0.1928)
0.1103
(0.0426 to 0.1536)
Treatment period 2
0.0917
(0.0474 to 0.1328)
0.0867
(0.0200 to 0.1931)
5.Secondary Outcome
Title Terminal Plasma Half-life (t1/2) of the Study Drug (Oxemet) and the Reference Drug (Glafornail) From 0 to 36 h
Hide Description Terminal phase half-life is the time required for the study drug to reduce to 50% of its concentration. t1/2 of Metformin was determined for each participant, both for Test and Reference products.
Time Frame From 0 to 36 h
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKP population
Arm/Group Title OXEMET 1000 mg Once Daily GLAFORNIL 1000 mg BID
Hide Arm/Group Description:
Eligible participants received single oral metformin (OXEMET) 1000 mg for one day in each of the two treatment periods in a randomized manner. Participants had a washout period of 7 days between two treatment periods and were followed up to 7 days after the last dose of the study drug.
Eligible participants received single oral metformin (GLAFORNIL) 500 mg BID for one day each in each of the two treatment periods in a randomized manner. Participants had a washout period of 7 days between two treatment periods and were followed up to 7 days after the last dose of the study drug.
Overall Number of Participants Analyzed 24 24
Median (Full Range)
Unit of Measure: h
Treatment period 1
7.08
(3.60 to 19.42)
6.29
(4.51 to 16.26)
Treatment period 2
7.59
(5.22 to 14.61)
8.00
(3.59 to 34.66)
6.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) of the Study Drug (Oxemet) and the Reference Drug (Glafornail) Over Period
Hide Description Time to reach maximum plasma concentration is the time at which Cmax of metformin was obtained for test and reference products.
Time Frame From 0 to 36 h
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKP population
Arm/Group Title OXEMET 1000 mg Once Daily GLAFORNIL 1000 mg BID
Hide Arm/Group Description:
Eligible participants received single oral metformin (OXEMET) 1000 mg for one day in each of the two treatment periods in a randomized manner. Participants had a washout period of 7 days between two treatment periods and were followed up to 7 days after the last dose of the study drug.
Eligible participants received single oral metformin (GLAFORNIL) 500 mg BID for one day each in each of the two treatment periods in a randomized manner. Participants had a washout period of 7 days between two treatment periods and were followed up to 7 days after the last dose of the study drug.
Overall Number of Participants Analyzed 24 24
Median (Full Range)
Unit of Measure: h
Treatment period 1
3.00
(1.00 to 5.00)
2.48
(1.50 to 4.03)
Treatment period 2
2.74
(1.03 to 4.03)
2.02
(0.48 to 3.50)
Time Frame Approximately up to 16 days
Adverse Event Reporting Description Safety population included all the participants who received at least one dose of the study drug.
 
Arm/Group Title OXEMET 1000 mg Once Daily GLAFORNIL 1000 mg BID
Hide Arm/Group Description Eligible participants received single oral metformin (OXEMET) 1000 milligrams (mg) for one day in each of the two treatment periods in a randomized manner. Participants had a washout period of 7 days between two treatment periods and were followed up to 7 days after the last dose of the study drug. Eligible participants received single oral metformin (GLAFORNIL) 500 milligrams (mg) twice daily (BID) for one day each in each of the two treatment periods in a randomized manner. Participants had a washout period of 7 days between two treatment periods and were followed up to 7 days after the last dose of the study drug.
All-Cause Mortality
OXEMET 1000 mg Once Daily GLAFORNIL 1000 mg BID
Affected / at Risk (%) Affected / at Risk (%)
Total   0/25 (0.00%)   0/24 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
OXEMET 1000 mg Once Daily GLAFORNIL 1000 mg BID
Affected / at Risk (%) Affected / at Risk (%)
Total   0/25 (0.00%)   0/24 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
OXEMET 1000 mg Once Daily GLAFORNIL 1000 mg BID
Affected / at Risk (%) Affected / at Risk (%)
Total   1/25 (4.00%)   0/24 (0.00%) 
Nervous system disorders     
Transient headache  1  1/25 (4.00%)  0/24 (0.00%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01842620     History of Changes
Other Study ID Numbers: 117219
First Submitted: April 25, 2013
First Posted: April 29, 2013
Results First Submitted: March 16, 2017
Results First Posted: December 22, 2017
Last Update Posted: December 22, 2017