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Relative Bioavailability of Two Different Batches of a Linagliptin / Metformin Combination Tablet in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01216397
First received: October 4, 2010
Last updated: January 17, 2013
Last verified: January 2013
History of Changes
Results First Received: February 3, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Bio-equivalence Study;   Intervention Model: Crossover Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Healthy
Interventions: Drug: Linagliptin/Metformin (standard batch)
Drug: Linagliptin/Metformin (side batch)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
Standard Batch Then Side Batch No text entered.
Side Batch Then Standard Batch No text entered.

Participant Flow:   Overall Study
    Standard Batch Then Side Batch     Side Batch Then Standard Batch  
STARTED     20     20  
COMPLETED     20     20  
NOT COMPLETED     0     0  



  Baseline Characteristics
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Reporting Groups
  Description
All Participants Treatment with standard batch and side batch

Baseline Measures
    All Participants  
Number of Participants  
[units: participants]
 		  40  
Age  
[units: Years]
Mean ± Standard Deviation 		  36.8  ± 6.8  
Gender  
[units: Participants]
 		 
Female     20  
Male     20  
Body mass index  
[units: kg/m^2]
Mean ± Standard Deviation 		  23.74  ± 2.74  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Linagliptin: Maximum Measured Concentration (Cmax)   [ Time Frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2 ]
  Show Outcome Measure 1

2.  Primary:   Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval 0 to 72 Hours (AUC0-72)   [ Time Frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2 ]
  Show Outcome Measure 2

3.  Primary:   Metformin: Cmax   [ Time Frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2 ]
  Show Outcome Measure 3

4.  Primary:   Metformin: AUC0-tz   [ Time Frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2 ]
  Show Outcome Measure 4

5.  Secondary:   Linagliptin: AUC0-infinity   [ Time Frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2 ]
  Show Outcome Measure 5

6.  Secondary:   Linagliptin: Percentage of AUCtz-∞ Obtained by Extrapolation   [ Time Frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2 ]
  Show Outcome Measure 6

7.  Secondary:   Linagliptin: Time to Maximum Measured Concentration of the Analyte in Plasma (Tmax)   [ Time Frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2 ]
  Show Outcome Measure 7

8.  Secondary:   Linagliptin: λz (Terminal Elimination Rate Constant in Plasma)   [ Time Frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2 ]
  Show Outcome Measure 8

9.  Secondary:   t1/2 (Terminal Half-life of the Analyte in Plasma)   [ Time Frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2 ]
  Show Outcome Measure 9

10.  Secondary:   Linagliptin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration)   [ Time Frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2 ]
  Show Outcome Measure 10

11.  Secondary:   Linagliptin: Apparent Clearance of the Analyte in Plasma After Extravascular Administration (CL/F)   [ Time Frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2 ]
  Show Outcome Measure 11

12.  Secondary:   Linagliptin: Apparent Volume of Distribution During the Terminal Phase Following an Extravascular Dose (Vz/F)   [ Time Frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2 ]
  Show Outcome Measure 12

13.  Secondary:   Metformin: AUC0-infinity   [ Time Frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2 ]
  Hide Outcome Measure 13

Measure Type Secondary
Measure Title Metformin: AUC0-infinity
Measure Description Geometric Mean of AUC0-infinity of Metformin
Time Frame Day 1 to 35 for period 1, and Day 36 to 70 for period 2  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated Set

Reporting Groups
  Description
Standard Batch standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Side Batch side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC

Measured Values
    Standard Batch     Side Batch  
Number of Participants Analyzed  
[units: participants]
 		  40     40  
Metformin: AUC0-infinity  
[units: ng*h/mL]
Geometric Mean ( Geometric Coefficient of Variation ) 		  12400  
  ( 21.2% )   		  12300  
  ( 19.9% )  


Statistical Analysis 1 for Metformin: AUC0-infinity
Groups [1] All groups
adjusted gMean ratio [2] 100.3
90% Confidence Interval ( 95.7 to 105.2 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Standard batch vs. Side batch
[2] Other relevant estimation information:
  No text entered.



14.  Secondary:   Metformin: Percentage of AUCtz-∞ Obtained by Extrapolation   [ Time Frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2 ]
  Show Outcome Measure 14

15.  Secondary:   Metformin: Tmax   [ Time Frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2 ]
  Show Outcome Measure 15

16.  Secondary:   Metformin: λz (Terminal Elimination Rate Constant in Plasma)   [ Time Frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2 ]
  Show Outcome Measure 16

17.  Secondary:   Metformin: t1/2 (Terminal Half-life of the Analyte in Plasma)   [ Time Frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2 ]
  Show Outcome Measure 17

18.  Secondary:   Metformin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration)   [ Time Frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2 ]
  Show Outcome Measure 18

19.  Secondary:   Metformin: CL/F   [ Time Frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2 ]
  Show Outcome Measure 19

20.  Secondary:   Metformin: Vz/F   [ Time Frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2 ]
  Show Outcome Measure 20

21.  Secondary:   Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities   [ Time Frame: Day 1 to 4 for period 1, and day 36 to 39 for period 2 ]
  Show Outcome Measure 21

22.  Secondary:   Participants With Treatment Emergent Adverse Events   [ Time Frame: Day 1 to 4 for period 1, and day 36 to 39 for period 2 ]
  Show Outcome Measure 22

23.  Secondary:   Participants Who Discontinued the Trial Because of an Adverse Event   [ Time Frame: Day 1 to 4 for period 1, and day 36 to 39 for period 2 ]
  Show Outcome Measure 23

24.  Secondary:   Assessment of Tolerability by the Investigator   [ Time Frame: Day 1 to 4 for period 1, and day 36 to 39 for period 2 ]
  Show Outcome Measure 24


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim Pharmaceuticals
phone: 1-800-243-0127
e-mail: clintriage.rdg@boehringer-ingelheim.com


No publications provided


Responsible Party: Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01216397     History of Changes
Other Study ID Numbers: 1288.6, 2010-019291-75
Study First Received: October 4, 2010
Results First Received: February 3, 2012
Last Updated: January 17, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices