Trial Outcomes & Findings for Glucophage® Extended Release (XR) 750 Milligram (mg) Indonesia Bioequivalence (BE) Study (NCT NCT03583385)
NCT ID: NCT03583385
Last Updated: 2019-11-25
Results Overview
The maximum plasma concentration of Metformin.
COMPLETED
PHASE1
48 participants
Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1
2019-11-25
Participant Flow
Participant milestones
| Measure |
First Glucophage XR (Test), Then Glucophage XR (Comparator)
Participants received single oral dose of 750 milligram (mg) Glucophage® XR tablet manufactured by PT Merck Tbk, Jakarta, Indonesia (Test Drug) in treatment period 1 followed by single oral dose of 750 mg Glucophage® XR tablet manufactured by Merck Santé, Semoy, France (Comparator Drug) in treatment period 2 under fasting conditions. The two periods were separated by a 7-day wash-out period.
|
First Glucophage XR (Comparator), Then Glucophage XR (Test)
Participants received single oral dose of 750 milligram (mg) Glucophage® XR tablet manufactured by Merck Santé, Semoy, France (Comparator Drug) in treatment period 1 followed by single oral dose of 750 mg Glucophage® XR tablet manufactured by PT Merck Tbk, Jakarta, Indonesia (Test Drug) in treatment period 2 under fasting conditions. The two periods were separated by a 7-day wash-out period.
|
|---|---|---|
|
Treatment Period 1
STARTED
|
24
|
24
|
|
Treatment Period 1
COMPLETED
|
23
|
23
|
|
Treatment Period 1
NOT COMPLETED
|
1
|
1
|
|
Treatment Period 2
STARTED
|
22
|
23
|
|
Treatment Period 2
COMPLETED
|
21
|
23
|
|
Treatment Period 2
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
First Glucophage XR (Test), Then Glucophage XR (Comparator)
Participants received single oral dose of 750 milligram (mg) Glucophage® XR tablet manufactured by PT Merck Tbk, Jakarta, Indonesia (Test Drug) in treatment period 1 followed by single oral dose of 750 mg Glucophage® XR tablet manufactured by Merck Santé, Semoy, France (Comparator Drug) in treatment period 2 under fasting conditions. The two periods were separated by a 7-day wash-out period.
|
First Glucophage XR (Comparator), Then Glucophage XR (Test)
Participants received single oral dose of 750 milligram (mg) Glucophage® XR tablet manufactured by Merck Santé, Semoy, France (Comparator Drug) in treatment period 1 followed by single oral dose of 750 mg Glucophage® XR tablet manufactured by PT Merck Tbk, Jakarta, Indonesia (Test Drug) in treatment period 2 under fasting conditions. The two periods were separated by a 7-day wash-out period.
|
|---|---|---|
|
Treatment Period 1
Withdrawal by Subject
|
1
|
1
|
|
Treatment Period 2
Adverse Event
|
1
|
0
|
Baseline Characteristics
Glucophage® Extended Release (XR) 750 Milligram (mg) Indonesia Bioequivalence (BE) Study
Baseline characteristics by cohort
| Measure |
All Participants
n=48 Participants
All participants who received Glucophage® XR 750 mg Tablet manufactured by PT Merck Tbk, Jakarta, Indonesia or Glucophage® XR 750 mg Tablet manufactured by Merck Santé, Semoy, France on Day 1 in either first treatment period or second treatment period.
|
|---|---|
|
Age, Continuous
|
33.5 Years
STANDARD_DEVIATION 10.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
36 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
48 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1Population: Pharmacokinetic (PK) analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results, with adequate study medication compliance, and who have valid primary endpoints for both treatment.
The maximum plasma concentration of Metformin.
Outcome measures
| Measure |
Glucophage XR (Test)
n=43 Participants
All participants who received Glucophage® XR 750 mg Tablet manufactured by PT Merck Tbk, Jakarta, Indonesia on Day 1 in either first treatment period or second treatment period.
|
Glucophage XR (Comparator)
n=43 Participants
All participants who received Glucophage® XR 750 mg Tablet (manufactured by Merck Santé, Semoy, France) on Day 1 in either first treatment period or second treatment period.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Metformin
|
1109 Nano-gram per milliliter (ng/mL)
Standard Deviation 318.4
|
1087 Nano-gram per milliliter (ng/mL)
Standard Deviation 336.3
|
PRIMARY outcome
Timeframe: Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1Population: PK analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results, with adequate study medication compliance, and who have valid primary endpoints for both treatment.
Area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration.
Outcome measures
| Measure |
Glucophage XR (Test)
n=43 Participants
All participants who received Glucophage® XR 750 mg Tablet manufactured by PT Merck Tbk, Jakarta, Indonesia on Day 1 in either first treatment period or second treatment period.
|
Glucophage XR (Comparator)
n=43 Participants
All participants who received Glucophage® XR 750 mg Tablet (manufactured by Merck Santé, Semoy, France) on Day 1 in either first treatment period or second treatment period.
|
|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin
|
7387 Nanogram*hour per milliliter (ng*h/mL)
Standard Deviation 2535.7
|
6977 Nanogram*hour per milliliter (ng*h/mL)
Standard Deviation 2512.0
|
SECONDARY outcome
Timeframe: Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1Population: PK analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results, with adequate study medication compliance, and who have valid primary endpoints for both treatment.
AUC (0-inf) is defined as the area under the plasma concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0-inf).
Outcome measures
| Measure |
Glucophage XR (Test)
n=43 Participants
All participants who received Glucophage® XR 750 mg Tablet manufactured by PT Merck Tbk, Jakarta, Indonesia on Day 1 in either first treatment period or second treatment period.
|
Glucophage XR (Comparator)
n=43 Participants
All participants who received Glucophage® XR 750 mg Tablet (manufactured by Merck Santé, Semoy, France) on Day 1 in either first treatment period or second treatment period.
|
|---|---|---|
|
Area Under Plasma Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin
|
7678 ng*h/mL
Standard Deviation 2559.5
|
7250 ng*h/mL
Standard Deviation 2523.6
|
SECONDARY outcome
Timeframe: Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1Population: PK analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results, with adequate study medication compliance, and who have valid primary endpoints for both treatment.
Time of the maximum drug concentration.
Outcome measures
| Measure |
Glucophage XR (Test)
n=43 Participants
All participants who received Glucophage® XR 750 mg Tablet manufactured by PT Merck Tbk, Jakarta, Indonesia on Day 1 in either first treatment period or second treatment period.
|
Glucophage XR (Comparator)
n=43 Participants
All participants who received Glucophage® XR 750 mg Tablet (manufactured by Merck Santé, Semoy, France) on Day 1 in either first treatment period or second treatment period.
|
|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metformin
|
3.50 Hours
Interval 2.0 to 6.0
|
3.00 Hours
Interval 1.5 to 6.0
|
SECONDARY outcome
Timeframe: Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1Population: PK analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results, with adequate study medication compliance, and who have valid primary endpoints for both treatment.
Elimination Half Life (t1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half.
Outcome measures
| Measure |
Glucophage XR (Test)
n=43 Participants
All participants who received Glucophage® XR 750 mg Tablet manufactured by PT Merck Tbk, Jakarta, Indonesia on Day 1 in either first treatment period or second treatment period.
|
Glucophage XR (Comparator)
n=43 Participants
All participants who received Glucophage® XR 750 mg Tablet (manufactured by Merck Santé, Semoy, France) on Day 1 in either first treatment period or second treatment period.
|
|---|---|---|
|
Terminal Elimination Half-life in Plasma (t½) of Metformin
|
5.82 Hours
Standard Deviation 2.875
|
6.03 Hours
Standard Deviation 3.292
|
SECONDARY outcome
Timeframe: Up to Day 51Population: The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment.
An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. Number of participants with TEAEs included participants with both non serious and serious TEAEs.
Outcome measures
| Measure |
Glucophage XR (Test)
n=47 Participants
All participants who received Glucophage® XR 750 mg Tablet manufactured by PT Merck Tbk, Jakarta, Indonesia on Day 1 in either first treatment period or second treatment period.
|
Glucophage XR (Comparator)
n=46 Participants
All participants who received Glucophage® XR 750 mg Tablet (manufactured by Merck Santé, Semoy, France) on Day 1 in either first treatment period or second treatment period.
|
|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Treatment Emergent Adverse Events (TEAEs)
|
5 Participants
|
9 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Serious TEAEs
|
0 Participants
|
0 Participants
|
Adverse Events
Glucophage XR (Test)
Glucophage XR (Comparator)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Glucophage XR (Test)
n=47 participants at risk
All participants who received Glucophage® XR 750 mg Tablet manufactured by PT Merck Tbk, Jakarta, Indonesia on Day 1 in either first treatment period or second treatment period.
|
Glucophage XR (Comparator)
n=46 participants at risk
All participants who received Glucophage® XR 750 mg Tablet (manufactured by Merck Santé, Semoy, France) on Day 1 in either first treatment period or second treatment period.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
2.1%
1/47 • Up to Day 51
The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment.
|
0.00%
0/46 • Up to Day 51
The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment.
|
|
Gastrointestinal disorders
Stools loose
|
4.3%
2/47 • Up to Day 51
The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment.
|
2.2%
1/46 • Up to Day 51
The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment.
|
|
Gastrointestinal disorders
Nausea
|
2.1%
1/47 • Up to Day 51
The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment.
|
8.7%
4/46 • Up to Day 51
The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment.
|
|
Nervous system disorders
Headache
|
8.5%
4/47 • Up to Day 51
The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment.
|
15.2%
7/46 • Up to Day 51
The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/47 • Up to Day 51
The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment.
|
2.2%
1/46 • Up to Day 51
The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment.
|
|
Skin and subcutaneous tissue disorders
Dermatitis venenata
|
2.1%
1/47 • Up to Day 51
The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment.
|
0.00%
0/46 • Up to Day 51
The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment.
|
|
Eye disorders
Conjunctival hyperaemia
|
0.00%
0/47 • Up to Day 51
The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment.
|
2.2%
1/46 • Up to Day 51
The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment.
|
|
Renal and urinary disorders
Urinary tract bleed microscopic
|
2.1%
1/47 • Up to Day 51
The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment.
|
2.2%
1/46 • Up to Day 51
The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment.
|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
0.00%
0/47 • Up to Day 51
The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment.
|
2.2%
1/46 • Up to Day 51
The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment.
|
Additional Information
Communication Center
Merck KGaA, Darmstadt, Germany
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place