Trial Outcomes & Findings for Comparison of the Bioavailability of Metformin Between Medium Dose Linagliptin/Metformin Tablets and Medium Dose Glucophage Tablet Given With Linagliptin Tablet (NCT NCT01383356)

NCT ID: NCT01383356

Last Updated: 2014-03-28

Results Overview

Maximum measured concentration of metformin in plasma, per period.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

58 participants

Primary outcome timeframe

Prior to drug administration and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 30, and 36 hours post dose in each treatment period

Results posted on

2014-03-28

Participant Flow

18 subjects were enrolled in the original study (June 2011 to July 2011) and 40 in the add-on study (November 2011 to December 2011) which was an option provided by protocol to increase the subject number. As no significant STUDY and STUDY-by-TREATMENT effect was revealed in analysis of pooled data, final analysis was performed on pooled data.

This is a 2 period, 2 sequence, 2 treatment crossover. Subjects were randomized to one of the two sequences AB or BA. The duration of washout was at least 35 days between dosing.

Participant milestones

Participant milestones
Measure	Lina/Met 2.5mg/500mg Then Lina 2.5mg Plus Met 500mg Combination tablet Linagliptin (Lina) /Metformin (Met) 2.5mg/500mg followed by single tablets Linagliptin 2.5mg plus Metformin 500mg	Lina 2.5mg Plus Met 500mg Then Lina/Met 2.5mg/500mg Single tablets Linagliptin 2.5mg plus Metformin 500mg followed by combination tablet Linagliptin/Metformin 2.5mg/500mg
Period 1 STARTED	29	29
Period 1 COMPLETED	21	23
Period 1 NOT COMPLETED	8	6
Washout Period (at Least 35 Days) STARTED	21	23
Washout Period (at Least 35 Days) COMPLETED	21	23
Washout Period (at Least 35 Days) NOT COMPLETED	0	0
Period 2 STARTED	21	23
Period 2 COMPLETED	21	23
Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Lina/Met 2.5mg/500mg Then Lina 2.5mg Plus Met 500mg Combination tablet Linagliptin (Lina) /Metformin (Met) 2.5mg/500mg followed by single tablets Linagliptin 2.5mg plus Metformin 500mg	Lina 2.5mg Plus Met 500mg Then Lina/Met 2.5mg/500mg Single tablets Linagliptin 2.5mg plus Metformin 500mg followed by combination tablet Linagliptin/Metformin 2.5mg/500mg
Period 1 Adverse Event	5	3
Period 1 Non-compliance	3	0
Period 1 Out of Range Mid-study-Test	0	1
Period 1 Personal	0	2

Baseline Characteristics

Comparison of the Bioavailability of Metformin Between Medium Dose Linagliptin/Metformin Tablets and Medium Dose Glucophage Tablet Given With Linagliptin Tablet

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Entire Study Population n=58 Participants Total number of subjects randomised and treated in the study.
Age, Continuous	35 years STANDARD_DEVIATION 9 • n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants

PRIMARY outcome

Timeframe: Prior to drug administration and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 30, and 36 hours post dose in each treatment period

Population: All subjects having all samples in all periods and subjects who missed samples that may not affect the estimation of pharmacokinetic parameters in any period.

Maximum measured concentration of metformin in plasma, per period.

Outcome measures

Outcome measures
Measure	Lina/Met 2.5mg/500mg n=44 Participants Combination tablet	Lina 2.5mg Plus Met 500mg n=44 Participants Single tablets
Maximum Plasma Concentration (Cmax)	901.82 ng/ml Standard Deviation 262.45	770.52 ng/ml Standard Deviation 189.44

PRIMARY outcome

Timeframe: Prior to drug administration and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 30, and 36 hours post dose in each treatment period

Population: All subjects having all samples in all periods and subjects who missed samples that may not affect the estimation of pharmacokinetic parameters in any period

AUC0-t is the area under the concentration versus time curve of metformin in plasma, from time zero (0) to the time of the last measurable analyte concentration (t), as calculated by the linear trapezoidal method.

Outcome measures

Outcome measures
Measure	Lina/Met 2.5mg/500mg n=44 Participants Combination tablet	Lina 2.5mg Plus Met 500mg n=44 Participants Single tablets
Area Under the Curve 0 to Last Measurable Value (AUC0-t)	7079.65 ng*h/ml Standard Deviation 1688.14	6808.27 ng*h/ml Standard Deviation 1708.20

SECONDARY outcome

Timeframe: Prior to drug administration and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 30, and 36 hours post dose in each treatment period

Population: All subjects having all samples in all periods and subjects who missed samples that may not affect the estimation of pharmacokinetic parameters in any period

AUC0-inf is the area under the concentration versus time curve of metformin in plasma from time zero extrapolated to infinity.

Outcome measures

Outcome measures
Measure	Lina/Met 2.5mg/500mg n=44 Participants Combination tablet	Lina 2.5mg Plus Met 500mg n=44 Participants Single tablets
Area Under the Curve 0 to Inf (AUC0-inf)	7198.79 ng*h/ml Standard Deviation 1689.89	6923.79 ng*h/ml Standard Deviation 1714.08

Adverse Events

Lina/Met 2.5mg/500mg

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Lina 2.5mg Plus Met 500mg

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Lina/Met 2.5mg/500mg n=52 participants at risk Combination tablet	Lina 2.5mg Plus Met 500mg n=50 participants at risk Single tablets
Gastrointestinal disorders Diarrhoea	0.00% 0/52 • Period 1 (36 hours)+ Washout (35 days) +Period 2 (36 hours)	6.0% 3/50 • Period 1 (36 hours)+ Washout (35 days) +Period 2 (36 hours)
Gastrointestinal disorders Nausea	17.3% 9/52 • Period 1 (36 hours)+ Washout (35 days) +Period 2 (36 hours)	16.0% 8/50 • Period 1 (36 hours)+ Washout (35 days) +Period 2 (36 hours)
Gastrointestinal disorders Vomiting	7.7% 4/52 • Period 1 (36 hours)+ Washout (35 days) +Period 2 (36 hours)	6.0% 3/50 • Period 1 (36 hours)+ Washout (35 days) +Period 2 (36 hours)
Metabolism and nutrition disorders Decreased appetite	0.00% 0/52 • Period 1 (36 hours)+ Washout (35 days) +Period 2 (36 hours)	6.0% 3/50 • Period 1 (36 hours)+ Washout (35 days) +Period 2 (36 hours)
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/52 • Period 1 (36 hours)+ Washout (35 days) +Period 2 (36 hours)	6.0% 3/50 • Period 1 (36 hours)+ Washout (35 days) +Period 2 (36 hours)
Nervous system disorders Dizziness	11.5% 6/52 • Period 1 (36 hours)+ Washout (35 days) +Period 2 (36 hours)	8.0% 4/50 • Period 1 (36 hours)+ Washout (35 days) +Period 2 (36 hours)
Nervous system disorders Headache	13.5% 7/52 • Period 1 (36 hours)+ Washout (35 days) +Period 2 (36 hours)	18.0% 9/50 • Period 1 (36 hours)+ Washout (35 days) +Period 2 (36 hours)

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
Publication restrictions are in place

Restriction type: OTHER