Trial Outcomes & Findings for Relative Bioavailability of Two Different Batches of a Linagliptin / Metformin Combination Tablet in Healthy Volunteers (NCT NCT01216397)
NCT ID: NCT01216397
Last Updated: 2014-06-27
Results Overview
Geometric mean of Cmax of Linagliptin
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
40 participants
Primary outcome timeframe
Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Results posted on
2014-06-27
Participant Flow
This was an open-label, single-dose, randomised, 2-way crossover trial. Subjects were equally randomised to one of two sequences, and in general terms, AB or BA. Hence, 20 subjects were in group AB and 20 in group BA. All 40 subjects received A and B. The numbers presented in the milestones are overall, which is consistent with the trial report.
Participant milestones
| Measure |
Standard Batch Then Side Batch
Linagliptin/metformin FDC tablet from standard batch, then Linagliptin/metformin FDC tablet from side batch
|
Side Batch Then Standard Batch
Linagliptin/metformin FDC tablet from side batch, then Linagliptin/metformin FDC tablet from standard batch
|
|---|---|---|
|
Period 1
STARTED
|
20
|
20
|
|
Period 1
COMPLETED
|
20
|
20
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
|
Washout (35 Days)
STARTED
|
20
|
20
|
|
Washout (35 Days)
COMPLETED
|
20
|
20
|
|
Washout (35 Days)
NOT COMPLETED
|
0
|
0
|
|
Period 2
STARTED
|
20
|
20
|
|
Period 2
COMPLETED
|
20
|
20
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Relative Bioavailability of Two Different Batches of a Linagliptin / Metformin Combination Tablet in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
All Participants
n=40 Participants
Treatment with standard batch and side batch
|
|---|---|
|
Age, Continuous
|
36.8 Years
STANDARD_DEVIATION 6.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
|
Body mass index
|
23.74 kg/m^2
STANDARD_DEVIATION 2.74 • n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1 to 35 for period 1, and Day 36 to 70 for period 2Population: Treated Set
Geometric mean of Cmax of Linagliptin
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Linagliptin: Maximum Measured Concentration (Cmax)
|
5.36 nmol/L
Geometric Coefficient of Variation 20.3
|
5.39 nmol/L
Geometric Coefficient of Variation 20.3
|
PRIMARY outcome
Timeframe: Day 1 to 35 for period 1, and Day 36 to 70 for period 2Population: Treated Set
Geometric mean of AUC0-72 of Linagliptin
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval 0 to 72 Hours (AUC0-72)
|
179 nmol*hr/L
Geometric Coefficient of Variation 21.6
|
179 nmol*hr/L
Geometric Coefficient of Variation 20.5
|
PRIMARY outcome
Timeframe: Day 1 to 35 for period 1, and Day 36 to 70 for period 2Population: Treated Set
Geometric Mean of Cmax of Metformin
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Metformin: Cmax
|
1790 ng/mL
Geometric Coefficient of Variation 23.0
|
1820 ng/mL
Geometric Coefficient of Variation 25.5
|
PRIMARY outcome
Timeframe: Day 1 to 35 for period 1, and Day 36 to 70 for period 2Population: Treated Set
Geometric Mean of AUC0-tz of Metformin
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Metformin: AUC0-tz
|
12100 ng*hr/mL
Geometric Coefficient of Variation 21.4
|
12100 ng*hr/mL
Geometric Coefficient of Variation 19.4
|
SECONDARY outcome
Timeframe: Day 1 to 35 for period 1, and Day 36 to 70 for period 2Population: Treated Set
Geometric mean of AUC0-infinity of Linagliptin
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Linagliptin: AUC0-infinity
|
267 nmol*hr/L
Geometric Coefficient of Variation 25.4
|
267 nmol*hr/L
Geometric Coefficient of Variation 23.6
|
SECONDARY outcome
Timeframe: Day 1 to 35 for period 1, and Day 36 to 70 for period 2Population: Treated Set
Geometric Mean of percentage of AUCtz-∞ of linagliptin, where percentage is the unit of measurement.
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Linagliptin: Percentage of AUCtz-∞ Obtained by Extrapolation
|
32.6 percentage
Geometric Coefficient of Variation 17.5
|
32.1 percentage
Geometric Coefficient of Variation 20.3
|
SECONDARY outcome
Timeframe: Day 1 to 35 for period 1, and Day 36 to 70 for period 2Population: Treated Set
Median of the t\_max of linagliptin
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Linagliptin: Time to Maximum Measured Concentration of the Analyte in Plasma (Tmax)
|
3.00 hr
Interval 0.667 to 6.02
|
3.00 hr
Interval 0.983 to 6.02
|
SECONDARY outcome
Timeframe: Day 1 to 35 for period 1, and Day 36 to 70 for period 2Population: Treated Set
Geometric mean of the λ\_z of linagliptin
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Linagliptin: λz (Terminal Elimination Rate Constant in Plasma)
|
0.0153 1/hr
Geometric Coefficient of Variation 17.1
|
0.0152 1/hr
Geometric Coefficient of Variation 21.6
|
SECONDARY outcome
Timeframe: Day 1 to 35 for period 1, and Day 36 to 70 for period 2Population: Treated Set
Geometric mean of the t1/2 of linagliptin
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
t1/2 (Terminal Half-life of the Analyte in Plasma)
|
45.4 hr
Geometric Coefficient of Variation 17.1
|
45.6 hr
Geometric Coefficient of Variation 21.6
|
SECONDARY outcome
Timeframe: Day 1 to 35 for period 1, and Day 36 to 70 for period 2Population: Treated Set
Geometric mean of the MRTpo of linagliptin
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Linagliptin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration)
|
64.6 hr
Geometric Coefficient of Variation 15.7
|
64.5 hr
Geometric Coefficient of Variation 19.5
|
SECONDARY outcome
Timeframe: Day 1 to 35 for period 1, and Day 36 to 70 for period 2Population: Treated Set
Geometric mean of the CL/F of linagliptin
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Linagliptin: Apparent Clearance of the Analyte in Plasma After Extravascular Administration (CL/F)
|
330 mL/min
Geometric Coefficient of Variation 25.4
|
330 mL/min
Geometric Coefficient of Variation 23.6
|
SECONDARY outcome
Timeframe: Day 1 to 35 for period 1, and Day 36 to 70 for period 2Population: Treated Set
Geometric mean of the Vz/F of linagliptin
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Linagliptin: Apparent Volume of Distribution During the Terminal Phase Following an Extravascular Dose (Vz/F)
|
1300 Liter
Geometric Coefficient of Variation 22.8
|
1300 Liter
Geometric Coefficient of Variation 24.6
|
SECONDARY outcome
Timeframe: Day 1 to 35 for period 1, and Day 36 to 70 for period 2Population: Treated Set
Geometric Mean of AUC0-infinity of Metformin
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Metformin: AUC0-infinity
|
12400 ng*h/mL
Geometric Coefficient of Variation 21.2
|
12300 ng*h/mL
Geometric Coefficient of Variation 19.9
|
SECONDARY outcome
Timeframe: Day 1 to 35 for period 1, and Day 36 to 70 for period 2Population: Treated Set
Geometric Mean of the percentage of AUCtz-infinity of Metformin, where percentage is the unit of measurement.
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Metformin: Percentage of AUCtz-∞ Obtained by Extrapolation
|
1.51 percentage
Geometric Coefficient of Variation 87.4
|
1.52 percentage
Geometric Coefficient of Variation 97.0
|
SECONDARY outcome
Timeframe: Day 1 to 35 for period 1, and Day 36 to 70 for period 2Population: Treated Set
Median of tmax of metformin
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Metformin: Tmax
|
1.99 hr
Interval 0.667 to 4.02
|
2.00 hr
Interval 0.65 to 4.02
|
SECONDARY outcome
Timeframe: Day 1 to 35 for period 1, and Day 36 to 70 for period 2Population: Treated Set
Geometric mean of λz of metformin
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Metformin: λz (Terminal Elimination Rate Constant in Plasma)
|
0.0493 1/hr
Geometric Coefficient of Variation 71.0
|
0.0514 1/hr
Geometric Coefficient of Variation 84.3
|
SECONDARY outcome
Timeframe: Day 1 to 35 for period 1, and Day 36 to 70 for period 2Population: Treated Set
Geometric mean of t1/2 of metformin
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Metformin: t1/2 (Terminal Half-life of the Analyte in Plasma)
|
14.1 hr
Geometric Coefficient of Variation 71.0
|
13.5 hr
Geometric Coefficient of Variation 84.3
|
SECONDARY outcome
Timeframe: Day 1 to 35 for period 1, and Day 36 to 70 for period 2Population: Treated Set
Geometric mean of MRTpo of metformin
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Metformin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration)
|
8.27 hr
Geometric Coefficient of Variation 31.1
|
8.23 hr
Geometric Coefficient of Variation 36.9
|
SECONDARY outcome
Timeframe: Day 1 to 35 for period 1, and Day 36 to 70 for period 2Population: Treated Set
Geometric mean of CL/F of metformin
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Metformin: CL/F
|
1350 mL/min
Geometric Coefficient of Variation 21.2
|
1350 mL/min
Geometric Coefficient of Variation 19.9
|
SECONDARY outcome
Timeframe: Day 1 to 35 for period 1, and Day 36 to 70 for period 2Population: Treated Set
Geometric mean of Vz/F of metformin
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Metformin: Vz/F
|
1640 Liter
Geometric Coefficient of Variation 74.3
|
1580 Liter
Geometric Coefficient of Variation 82.4
|
SECONDARY outcome
Timeframe: Day 1 to 4 for period 1, and day 36 to 39 for period 2Population: Treated Set
12-lead-Electrocardiogram (ECG), vital sign (blood pressure and pulse rate), physical finding and laboratory abnormalities
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities
Vital sign abnormalities
|
0 Participants
|
0 Participants
|
|
Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities
Physical examination abnormalities
|
0 Participants
|
0 Participants
|
|
Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities
ECG abnormalities
|
0 Participants
|
0 Participants
|
|
Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities
Laboratory finding abnormalities
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 1 to 4 for period 1, and day 36 to 39 for period 2Population: Treated Set
Number of patients with treatment emergent AEs
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Participants With Treatment Emergent Adverse Events
Headache
|
6 Participants
|
9 Participants
|
|
Participants With Treatment Emergent Adverse Events
Nausea
|
0 Participants
|
1 Participants
|
|
Participants With Treatment Emergent Adverse Events
Vomiting
|
2 Participants
|
1 Participants
|
|
Participants With Treatment Emergent Adverse Events
Fatigue
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 1 to 4 for period 1, and day 36 to 39 for period 2Population: Treated Set
Number of participants who discontinued the trial because of an adverse event
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Participants Who Discontinued the Trial Because of an Adverse Event
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 1 to 4 for period 1, and day 36 to 39 for period 2Population: Treated Set
Qualitative variable assessing the tolerability by the investigator
Outcome measures
| Measure |
Standard Batch
n=40 Participants
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Side Batch
n=40 Participants
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Assessment of Tolerability by the Investigator
Good
|
39 Participants
|
40 Participants
|
|
Assessment of Tolerability by the Investigator
Not satisfactory
|
1 Participants
|
0 Participants
|
Adverse Events
Side Batch
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Standard Batch
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Side Batch
n=40 participants at risk
side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
Standard Batch
n=40 participants at risk
standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
|
|---|---|---|
|
Nervous system disorders
Headache
|
27.5%
11/40 • 4 days (period 1) + 4 days (treatment period 2)
Two identical treatment periods with an interval of at least 35 days between drug administrations.
|
17.5%
7/40 • 4 days (period 1) + 4 days (treatment period 2)
Two identical treatment periods with an interval of at least 35 days between drug administrations.
|
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 - 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