Trial Outcomes & Findings for Assessing the PK of Met DR, Met IR, and Met XR in Healthy Subjects (NCT NCT02291510)
NCT ID: NCT02291510
Last Updated: 2016-12-02
Results Overview
AUC (0-t) = Area under the curve from the time of dosing (0 h) to the time of the last quantifiable concentration after the standardized dinner. Doses were administered 1 min prior to 0 h (standardized dinner) for once daily in the evening (qPM) and twice daily (BID) dosing and 1 min prior to 12 h (standardized breakfast) for once daily in the morning (qAM) and BID dosing.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
20 participants
Primary outcome timeframe
Time points to create AUC (0-t) were: t = -0.08, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 11.92, 12.5, 13, 13.5, 14, 14.5, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24 hours relative to the start time of the standardized dinner.
Results posted on
2016-12-02
Participant Flow
Participant milestones
| Measure |
Sequence 1: ABDC
Treatment A = 1000 mg Met IR BID Treatment B = 500 mg Met DR BID Treatment C = 1000 mg Met DR BID Treatment D = 2000 mg Met XR QD
|
Sequence 2: BCAD
Treatment A = 1000 mg Met IR BID Treatment B = 500 mg Met DR BID Treatment C = 1000 mg Met DR BID Treatment D = 2000 mg Met XR QD
|
Sequence 3: CDBA
Treatment A = 1000 mg Met IR BID Treatment B = 500 mg Met DR BID Treatment C = 1000 mg Met DR BID Treatment D = 2000 mg Met XR QD
|
Sequence 4: DACB
Treatment A = 1000 mg Met IR BID Treatment B = 500 mg Met DR BID Treatment C = 1000 mg Met DR BID Treatment D = 2000 mg Met XR QD
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
5
|
5
|
5
|
5
|
|
Overall Study
Completed Treatment A
|
5
|
5
|
5
|
5
|
|
Overall Study
Completed Treatment B
|
5
|
5
|
5
|
4
|
|
Overall Study
Completed Treatment C
|
5
|
5
|
5
|
4
|
|
Overall Study
Completed Treatment D
|
5
|
5
|
5
|
5
|
|
Overall Study
COMPLETED
|
5
|
5
|
5
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Sequence 1: ABDC
Treatment A = 1000 mg Met IR BID Treatment B = 500 mg Met DR BID Treatment C = 1000 mg Met DR BID Treatment D = 2000 mg Met XR QD
|
Sequence 2: BCAD
Treatment A = 1000 mg Met IR BID Treatment B = 500 mg Met DR BID Treatment C = 1000 mg Met DR BID Treatment D = 2000 mg Met XR QD
|
Sequence 3: CDBA
Treatment A = 1000 mg Met IR BID Treatment B = 500 mg Met DR BID Treatment C = 1000 mg Met DR BID Treatment D = 2000 mg Met XR QD
|
Sequence 4: DACB
Treatment A = 1000 mg Met IR BID Treatment B = 500 mg Met DR BID Treatment C = 1000 mg Met DR BID Treatment D = 2000 mg Met XR QD
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Assessing the PK of Met DR, Met IR, and Met XR in Healthy Subjects
Baseline characteristics by cohort
| Measure |
Sequence 1: ABDC
n=5 Participants
Treatment A = 1000 mg Met IR BID Treatment B = 500 mg Met DR BID Treatment C = 1000 mg Met DR BID Treatment D = 2000 mg Met XR QD
|
Sequence 2: BCAD
n=5 Participants
Treatment A = 1000 mg Met IR BID Treatment B = 500 mg Met DR BID Treatment C = 1000 mg Met DR BID Treatment D = 2000 mg Met XR QD
|
Sequence 3: CDBA
n=5 Participants
Treatment A = 1000 mg Met IR BID Treatment B = 500 mg Met DR BID Treatment C = 1000 mg Met DR BID Treatment D = 2000 mg Met XR QD
|
Sequence 4: DACB
n=5 Participants
Treatment A = 1000 mg Met IR BID Treatment B = 500 mg Met DR BID Treatment C = 1000 mg Met DR BID Treatment D = 2000 mg Met XR QD
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
34.2 years
STANDARD_DEVIATION 13.6 • n=5 Participants
|
34.8 years
STANDARD_DEVIATION 13.1 • n=7 Participants
|
33.8 years
STANDARD_DEVIATION 9.2 • n=5 Participants
|
25.8 years
STANDARD_DEVIATION 5.0 • n=4 Participants
|
32.2 years
STANDARD_DEVIATION 10.6 • n=21 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
14 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
17 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Body Mass Index (BMI)
|
30.1 kg/m^2
STANDARD_DEVIATION 4.0 • n=5 Participants
|
29.5 kg/m^2
STANDARD_DEVIATION 2.8 • n=7 Participants
|
28.7 kg/m^2
STANDARD_DEVIATION 2.8 • n=5 Participants
|
30.0 kg/m^2
STANDARD_DEVIATION 1.8 • n=4 Participants
|
29.6 kg/m^2
STANDARD_DEVIATION 2.8 • n=21 Participants
|
PRIMARY outcome
Timeframe: Time points to create AUC (0-t) were: t = -0.08, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 11.92, 12.5, 13, 13.5, 14, 14.5, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24 hours relative to the start time of the standardized dinner.Population: Evaluable Population
AUC (0-t) = Area under the curve from the time of dosing (0 h) to the time of the last quantifiable concentration after the standardized dinner. Doses were administered 1 min prior to 0 h (standardized dinner) for once daily in the evening (qPM) and twice daily (BID) dosing and 1 min prior to 12 h (standardized breakfast) for once daily in the morning (qAM) and BID dosing.
Outcome measures
| Measure |
500 mg Met DR BID
n=19 Participants
Two doses of 500 mg Metformin Delayed-Release
Met DR: metformin delayed-release tablets
|
1000 mg Met DR BID
n=19 Participants
Two doses of 1000 mg Metformin Delayed-Release
Met DR: metformin delayed-release tablets
|
1000 mg Met IR BID
n=19 Participants
Two doses of 1000 mg Metformin Immediate-Release
Met IR: metformin immediate-release tablets
|
2000 mg Met XR QD
n=19 Participants
Single dose of 2000 mg Metformin Extended-Release
Met XR: metformin extended-release tablets
|
|---|---|---|---|---|
|
AUC (0-t) of Plasma Metformin
|
6164 ng*h/mL
Standard Error 465
|
9014 ng*h/mL
Standard Error 610
|
18709 ng*h/mL
Standard Error 1044
|
16989 ng*h/mL
Standard Error 968
|
PRIMARY outcome
Timeframe: Time points to create Cmax were: t = -0.08, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 11.92, 12.5, 13, 13.5, 14, 14.5, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24 hours relative to the start time of the standardized dinner.Population: Evaluable Population
Cmax = Maximum concentration from the first dose of study medication administration (0 h) to the time of the last quantifiable concentration following dose administration. Doses were administered 1 min prior to 0 h (standardized dinner) for qPM and BID dosing and 1 min prior to 12 h (standardized breakfast) for qAM and BID dosing.
Outcome measures
| Measure |
500 mg Met DR BID
n=19 Participants
Two doses of 500 mg Metformin Delayed-Release
Met DR: metformin delayed-release tablets
|
1000 mg Met DR BID
n=19 Participants
Two doses of 1000 mg Metformin Delayed-Release
Met DR: metformin delayed-release tablets
|
1000 mg Met IR BID
n=19 Participants
Two doses of 1000 mg Metformin Immediate-Release
Met IR: metformin immediate-release tablets
|
2000 mg Met XR QD
n=19 Participants
Single dose of 2000 mg Metformin Extended-Release
Met XR: metformin extended-release tablets
|
|---|---|---|---|---|
|
Cmax of Plasma Metformin
|
607 ng/mL
Standard Error 33
|
905 ng/mL
Standard Error 56
|
1328 ng/mL
Standard Error 63
|
1688 ng/mL
Standard Error 97
|
Adverse Events
500 mg Met DR BID
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
1000 mg Met DR BID
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
1000 mg Met IR BID
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
2000 mg Met XR QD
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
500 mg Met DR BID
n=19 participants at risk
Two doses of 500 mg Metformin Delayed-Release
Met DR: metformin delayed-release tablets
|
1000 mg Met DR BID
n=19 participants at risk
Two doses of 1000 mg Metformin Delayed-Release
Met DR: metformin delayed-release tablets
|
1000 mg Met IR BID
n=20 participants at risk
Two doses of 1000 mg Metformin Immediate-Release
Met IR: metformin immediate-release tablets
|
2000 mg Met XR QD
n=20 participants at risk
Single dose of 2000 mg Metformin Extended-Release
Met XR: metformin extended-release tablets
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
5.3%
1/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
5.0%
1/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
10.0%
2/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
|
Gastrointestinal disorders
Nausea
|
5.3%
1/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
10.0%
2/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
|
Gastrointestinal disorders
Vomiting
|
5.3%
1/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
5.3%
1/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
10.0%
2/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
|
Nervous system disorders
Headache
|
10.5%
2/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
10.0%
2/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
10.0%
2/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
5.0%
1/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
|
General disorders
Catheter Site Pain
|
5.3%
1/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
5.0%
1/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
5.0%
1/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
|
General disorders
Catheter Site Related Reaction
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
5.0%
1/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
|
General disorders
Fatigue
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
5.0%
1/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
|
General disorders
Vessel Puncture Site Haematoma
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
5.0%
1/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
|
General disorders
Vessel Puncture Site Pain
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
5.0%
1/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
|
Psychiatric disorders
Anxiety
|
5.3%
1/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
5.3%
1/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
5.0%
1/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
|
Respiratory, thoracic and mediastinal disorders
Dry Throat
|
5.3%
1/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
5.3%
1/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/19 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
0.00%
0/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
5.0%
1/20 • Approximately 18 to 57 days depending on the number of days between the start of Visit 1 and Visit 2 and the number of washout days between the treatment visits
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The results of the Study may be published by INSTITUTE, however the publication shall not disclose any SPONSOR Confidential Information, the INSTITUTE shall send the SPONSOR a copy of any such proposed publication 90 days prior to submission for publication, the INSTITUTE, on request of the SPONSOR, shall delete any SPONSOR Confidential Information in the proposed publication, and the INSTITUTE shall, on the SPONSOR's request, delay submission while the SPONSOR files applications for patents.
- Publication restrictions are in place
Restriction type: OTHER