Trial Outcomes & Findings for 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. (NCT NCT01842620)
NCT ID: NCT01842620
Last Updated: 2017-12-22
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
25 participants
Primary outcome timeframe
From 0 to 36 hours (h)
Results posted on
2017-12-22
Participant Flow
This study was conducted from 13 Mar 2013 to 04 May 2013 at single center in Argentina.
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.
Participant milestones
| Measure |
OXEMET Then GLAFORNIL
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.
|
GLAFORNIL Then OXEMET
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 1
STARTED
|
13
|
12
|
|
Period 1
COMPLETED
|
12
|
12
|
|
Period 1
NOT COMPLETED
|
1
|
0
|
|
Washout Period
STARTED
|
12
|
12
|
|
Washout Period
COMPLETED
|
12
|
12
|
|
Washout Period
NOT COMPLETED
|
0
|
0
|
|
Period 2
STARTED
|
12
|
12
|
|
Period 2
COMPLETED
|
12
|
12
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
OXEMET Then GLAFORNIL
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.
|
GLAFORNIL Then OXEMET
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 1
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
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.
Baseline characteristics by cohort
| Measure |
Total Population
n=25 Participants
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
|
|---|---|
|
Age, Continuous
|
27.8 Years
STANDARD_DEVIATION 7.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
25 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From 0 to 36 hours (h)Population: PK parameters \[PKP\] population included all the participants who underwent plasma PK sampling and had evaluable area under curve assay results.
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.
Outcome measures
| Measure |
OXEMET 1000 mg Once Daily
n=24 Participants
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.
|
GLAFORNIL 1000 mg BID
n=24 Participants
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.
|
|---|---|---|
|
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)
Period 1
|
12348 nanogram* h/millilitre (ng*h/mL)
Geometric Coefficient of Variation 27
|
12727 nanogram* h/millilitre (ng*h/mL)
Geometric Coefficient of Variation 22
|
|
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)
Period 2
|
13470 nanogram* h/millilitre (ng*h/mL)
Geometric Coefficient of Variation 26
|
13069 nanogram* h/millilitre (ng*h/mL)
Geometric Coefficient of Variation 24
|
PRIMARY outcome
Timeframe: From 0 to 36 hPopulation: PKP population included all the participants who underwent plasma PK sampling and had evaluable area under curve assay results
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.
Outcome measures
| Measure |
OXEMET 1000 mg Once Daily
n=24 Participants
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.
|
GLAFORNIL 1000 mg BID
n=24 Participants
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.
|
|---|---|---|
|
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
Period 1
|
12636 ng*h/mL
Geometric Coefficient of Variation 26
|
13171 ng*h/mL
Geometric Coefficient of Variation 21
|
|
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
Period 2
|
13902 ng*h/mL
Geometric Coefficient of Variation 25
|
13604 ng*h/mL
Geometric Coefficient of Variation 22
|
PRIMARY outcome
Timeframe: From 0 to 36 hPopulation: PKP population
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.
Outcome measures
| Measure |
OXEMET 1000 mg Once Daily
n=24 Participants
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.
|
GLAFORNIL 1000 mg BID
n=24 Participants
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.
|
|---|---|---|
|
Geometric Means for Maximum Plasma Concentration of the Study Drug (Oxemet) to the Reference Drug (Glafornail) From 0 to 36 h
Period 1
|
2031.5 ng/mL
Geometric Coefficient of Variation 32
|
2097.8 ng/mL
Geometric Coefficient of Variation 23
|
|
Geometric Means for Maximum Plasma Concentration of the Study Drug (Oxemet) to the Reference Drug (Glafornail) From 0 to 36 h
Period 2
|
2124.5 ng/mL
Geometric Coefficient of Variation 28
|
2127.4 ng/mL
Geometric Coefficient of Variation 25
|
SECONDARY outcome
Timeframe: From 0 to 36 hPopulation: PKP population
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.
Outcome measures
| Measure |
OXEMET 1000 mg Once Daily
n=24 Participants
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.
|
GLAFORNIL 1000 mg BID
n=24 Participants
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.
|
|---|---|---|
|
The Elimination Constant (Kel) of the Study Drug (Oxemet) and the Reference Drug (Glafornail) From 0 to 36 h
Treatment period 1
|
0.0981 Per hour
Interval 0.0357 to 0.1928
|
0.1103 Per hour
Interval 0.0426 to 0.1536
|
|
The Elimination Constant (Kel) of the Study Drug (Oxemet) and the Reference Drug (Glafornail) From 0 to 36 h
Treatment period 2
|
0.0917 Per hour
Interval 0.0474 to 0.1328
|
0.0867 Per hour
Interval 0.02 to 0.1931
|
SECONDARY outcome
Timeframe: From 0 to 36 hPopulation: PKP population
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.
Outcome measures
| Measure |
OXEMET 1000 mg Once Daily
n=24 Participants
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.
|
GLAFORNIL 1000 mg BID
n=24 Participants
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.
|
|---|---|---|
|
Terminal Plasma Half-life (t1/2) of the Study Drug (Oxemet) and the Reference Drug (Glafornail) From 0 to 36 h
Treatment period 1
|
7.08 h
Interval 3.6 to 19.42
|
6.29 h
Interval 4.51 to 16.26
|
|
Terminal Plasma Half-life (t1/2) of the Study Drug (Oxemet) and the Reference Drug (Glafornail) From 0 to 36 h
Treatment period 2
|
7.59 h
Interval 5.22 to 14.61
|
8.00 h
Interval 3.59 to 34.66
|
SECONDARY outcome
Timeframe: From 0 to 36 hPopulation: PKP population
Time to reach maximum plasma concentration is the time at which Cmax of metformin was obtained for test and reference products.
Outcome measures
| Measure |
OXEMET 1000 mg Once Daily
n=24 Participants
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.
|
GLAFORNIL 1000 mg BID
n=24 Participants
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.
|
|---|---|---|
|
Time to Reach Maximum Plasma Concentration (Tmax) of the Study Drug (Oxemet) and the Reference Drug (Glafornail) Over Period
Treatment period 1
|
3.00 h
Interval 1.0 to 5.0
|
2.48 h
Interval 1.5 to 4.03
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of the Study Drug (Oxemet) and the Reference Drug (Glafornail) Over Period
Treatment period 2
|
2.74 h
Interval 1.03 to 4.03
|
2.02 h
Interval 0.48 to 3.5
|
Adverse Events
OXEMET 1000 mg Once Daily
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
GLAFORNIL 1000 mg BID
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
OXEMET 1000 mg Once Daily
n=25 participants at risk
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.
|
GLAFORNIL 1000 mg BID
n=24 participants at risk
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.
|
|---|---|---|
|
Nervous system disorders
Transient headache
|
4.0%
1/25 • Approximately up to 16 days
Safety population included all the participants who received at least one dose of the study drug.
|
0.00%
0/24 • Approximately up to 16 days
Safety population included all the participants who received at least one dose of the study drug.
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER