Trial Outcomes & Findings for Two-way Crossover Study in Healthy Male and Female Subjects to Evaluate the Bioequivalence of Jentadueto®. (NCT NCT01947153)

NCT ID: NCT01947153

Last Updated: 2015-02-25

Results Overview

Linagliptin: AUC 0-72 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 72 hours)

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

36 participants

Primary outcome timeframe

2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration

Results posted on

2015-02-25

Participant Flow

Participant milestones

Participant milestones
Measure	Fixed Dose Combination First, Then Free Combination 5 mg linagliptin / 1000mg metformin given as two 2.5mg linagliptin / 500mg metformin fixed dose combination (FDC) tablets first; then free combination: one 5mg linagliptin tablet and one 1000mg metformin tablet	Free Combination First, Then Fixed Dose Combination Free combination: one 5mg linagliptin tablet and one 1000mg metformin tablet first; then 5 mg linagliptin / 1000mg metformin given as two 2.5mg linagliptin / 500mg metformin fixed dose combination (FDC) tablets
Test Period 1 STARTED	18	18
Test Period 1 COMPLETED	18	18
Test Period 1 NOT COMPLETED	0	0
Test Period 2 STARTED	18	18
Test Period 2 COMPLETED	18	18
Test Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Two-way Crossover Study in Healthy Male and Female Subjects to Evaluate the Bioequivalence of Jentadueto®.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Subjects n=36 Participants All subjects treated with 5 mg linagliptin / 1000 mg metformin as fixed dose combination or as free dose combination.
Age, Continuous	25.0 years STANDARD_DEVIATION 6.2 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration

Population: subject set for the evaluation of pharmacokinetic endpoints of linagliptin (PKS-L): includes all subjects of the TS who provided at least 1 observation for at least 1 primary endpoint for linagliptin and had no important protocol violations with respect to the statistical evaluation of pharmacokinetic endpoints of linagliptin

Linagliptin: AUC 0-72 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 72 hours)

Outcome measures

Outcome measures
Measure	Fixed Dose Combination n=36 Participants Linagliptin/Metformin Linagliptin: Fixed dose combination: 2x 2.5mg Metformin: Combination: 500mg	Free Combination n=34 Participants Linagliptin and Metformin Metformin: Free combination 5mg Linagliptin: Free combination 1000mg
Linagliptin: AUC 0-72 (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to 72 Hours)	293 nmol*h/L Geometric Coefficient of Variation 23.4	288 nmol*h/L Geometric Coefficient of Variation 22.9

PRIMARY outcome

Timeframe: 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration

Population: The subject set for the evaluation of pharmacokinetic endpoints of metformin (PKS-M): includes all subjects of the TS who provided at least 1 observation for at least 1 primary endpoint for metformin and had no important protocol violations with respect to the statistical evaluation of pharmacokinetic endpoints of metformin

Metformin: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)

Outcome measures

Outcome measures
Measure	Fixed Dose Combination n=36 Participants Linagliptin/Metformin Linagliptin: Fixed dose combination: 2x 2.5mg Metformin: Combination: 500mg	Free Combination n=34 Participants Linagliptin and Metformin Metformin: Free combination 5mg Linagliptin: Free combination 1000mg
Metformin: AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point)	13000 ng*h/mL Geometric Coefficient of Variation 27.3	12100 ng*h/mL Geometric Coefficient of Variation 24.2

PRIMARY outcome

Timeframe: 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration

Population: PKS-L: includes all subjects of the TS who provided at least 1 observation for at least 1 primary endpoint for linagliptin and had no important protocol violations with respect to the statistical evaluation of pharmacokinetic endpoints of linagliptin

Linagliptin: Cmax (maximum measured concentration of the analyte in plasma)

Outcome measures

Outcome measures
Measure	Fixed Dose Combination n=36 Participants Linagliptin/Metformin Linagliptin: Fixed dose combination: 2x 2.5mg Metformin: Combination: 500mg	Free Combination n=34 Participants Linagliptin and Metformin Metformin: Free combination 5mg Linagliptin: Free combination 1000mg
Linagliptin: Cmax (Maximum Measured Concentration of the Analyte in Plasma)	10.3 nmol/L Geometric Coefficient of Variation 36.4	9.57 nmol/L Geometric Coefficient of Variation 36.2

PRIMARY outcome

Timeframe: 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration

Population: PKS-M: includes all subjects of the TS who provided at least 1 observation for at least 1 primary endpoint for metformin and had no important protocol violations with respect to the statistical evaluation of pharmacokinetic endpoints of metformin

Metformin: Cmax (maximum measured concentration of the analyte in plasma)

Outcome measures

Outcome measures
Measure	Fixed Dose Combination n=36 Participants Linagliptin/Metformin Linagliptin: Fixed dose combination: 2x 2.5mg Metformin: Combination: 500mg	Free Combination n=34 Participants Linagliptin and Metformin Metformin: Free combination 5mg Linagliptin: Free combination 1000mg
Metformin: Cmax (Maximum Measured Concentration of the Analyte in Plasma)	1840 ng/mL Geometric Coefficient of Variation 28.2	1700 ng/mL Geometric Coefficient of Variation 27.0

SECONDARY outcome

Timeframe: 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration

Population: PKS-L: includes all subjects of the TS who provided at least 1 observation for at least 1 primary endpoint for linagliptin and had no important protocol violations with respect to the statistical evaluation of pharmacokinetic endpoints of linagliptin

Linagliptin: AUC 0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)

Outcome measures

Outcome measures
Measure	Fixed Dose Combination n=36 Participants Linagliptin/Metformin Linagliptin: Fixed dose combination: 2x 2.5mg Metformin: Combination: 500mg	Free Combination n=34 Participants Linagliptin and Metformin Metformin: Free combination 5mg Linagliptin: Free combination 1000mg
Linagliptin: AUC 0-inf (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity)	467 nmol*h/L Geometric Coefficient of Variation 25.8	479 nmol*h/L Geometric Coefficient of Variation 29.5

SECONDARY outcome

Timeframe: 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration

Population: PKS-M: includes all subjects of the TS who provided at least 1 observation for at least 1 primary endpoint for metformin and had no important protocol violations with respect to the statistical evaluation of pharmacokinetic endpoints of metformin

Metformin: AUC 0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)

Outcome measures

Outcome measures
Measure	Fixed Dose Combination n=36 Participants Linagliptin/Metformin Linagliptin: Fixed dose combination: 2x 2.5mg Metformin: Combination: 500mg	Free Combination n=34 Participants Linagliptin and Metformin Metformin: Free combination 5mg Linagliptin: Free combination 1000mg
Metformin: AUC 0-inf (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity)	13400 ng*h/mL Geometric Coefficient of Variation 26.8	12500 ng*h/mL Geometric Coefficient of Variation 24.1

SECONDARY outcome

Timeframe: 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration

Population: PKS-L: includes all subjects of the TS who provided at least 1 observation for at least 1 primary endpoint for linagliptin and had no important protocol violations with respect to the statistical evaluation of pharmacokinetic endpoints of linagliptin

Linagliptin: AUC 0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)

Outcome measures

Outcome measures
Measure	Fixed Dose Combination n=36 Participants Linagliptin/Metformin Linagliptin: Fixed dose combination: 2x 2.5mg Metformin: Combination: 500mg	Free Combination n=34 Participants Linagliptin and Metformin Metformin: Free combination 5mg Linagliptin: Free combination 1000mg
Linagliptin: AUC 0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point)	293 nmol*h/L Geometric Coefficient of Variation 23.4	288 nmol*h/L Geometric Coefficient of Variation 22.9

Adverse Events

Fixed Dose Combination

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Free Combination

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Fixed Dose Combination n=36 participants at risk Linagliptin/Metformin Linagliptin: Fixed dose combination: 2x 2.5mg Metformin: Combination: 500mg	Free Combination n=36 participants at risk Linagliptin and Metformin Metformin: Free combination 5mg Linagliptin: Free combination 1000mg
Nervous system disorders Headache	2.8% 1/36 • From first study drug administration until 30±2 days after the last study drug administration	11.1% 4/36 • From first study drug administration until 30±2 days after the last study drug administration

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 Other - Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER