30 Week Parallel Group Comparison Study of Linagliptin + Pioglitazone (5+15, 5+30 and 5+45 mg) qd Versus Respective Monotherapies, Followed by a Comparison of 5mg+30mg and 5mg+45mg Versus Respective Monotherapies in Type 2 Diabetes for up to 54 Weeks

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01183013
First received: August 16, 2010
Last updated: June 3, 2014
Last verified: May 2014
Results First Received: March 12, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double-Blind;   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: Pioglitazone 15 mg
Drug: Pioglitazone 45 mg
Drug: Pioglitazone 30 mg
Drug: Linagliptin 5mg / Pioglitazone 45 mg FDC
Drug: Linagliptin 5mg / Pioglitazone 30 mg FDC
Drug: Linagliptin 5mg
Drug: Linagliptin 5mg / Pioglitazone 15 mg FDC

  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
After Amendment #5, patients were considered COMPLETED at the end of Part A (30 weeks) or after their next Part B visit (up to 54 weeks) if already in Part B. Before Amendment #5, all patients were considered COMPLETED at the end of Part A + Part B (84 weeks).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Pio15/Pio30 Participants treated with pioglitazone 15mg for 30 weeks followed by pioglitazone 30mg for up to 54 weeks.
Pio30/Pio30 Participants treated with pioglitazone 30mg for 30 weeks followed by pioglitazone 30mg for up to 54 weeks.
Pio45/Pio45 Participants treated with pioglitazone 30 mg for 6 weeks and then were titrated up to pioglitazone 45mg for 24 weeks followed by pioglitazone 45mg for up to 54 weeks.
Lina5/Lina5 Participants treated with linagliptin 5mg once daily for 30 weeks followed by linagliptin 5mg once daily for up to 54 weeks.
Lina5Pio15/Lina5Pio30 Participants treated with linagliptin 5mg + pioglitazone 15mg fixed dose combination (FDC) for 30 weeks followed by linagliptin 5mg + pioglitazone 30mg FDC for up to 54 weeks.
Lina5Pio30/Lina5Pio30 Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for 30 weeks followed by linagliptin 5mg + pioglitazone 30mg FDC for up to 54 weeks.
Lina5Pio45/Lina5Pio45 Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for 6 weeks and linagliptin 5mg + pioglitazone 45mg FDC for 24 weeks followed by linagliptin 5mg + pioglitazone 45mg FDC for up to 54 weeks.

Participant Flow:   Overall Study
    Pio15/Pio30     Pio30/Pio30     Pio45/Pio45     Lina5/Lina5     Lina5Pio15/Lina5Pio30     Lina5Pio30/Lina5Pio30     Lina5Pio45/Lina5Pio45  
STARTED     131     140     138     135     126     133     133  
COMPLETED     86 [1]   101 [1]   97 [1]   105 [1]   90 [1]   88 [1]   96 [1]
NOT COMPLETED     45     39     41     30     36     45     37  
Adverse Event                 6                 8                 5                 5                 10                 10                 6  
Lack of Efficacy                 3                 2                 1                 2                 1                 2                 0  
Protocol Violation                 5                 2                 4                 0                 4                 3                 3  
Lost to Follow-up                 7                 3                 4                 3                 2                 6                 5  
Withdrawal by Subject                 9                 13                 10                 8                 7                 9                 10  
Reasons other than stated above                 15                 11                 17                 12                 12                 15                 13  
[1] Completed is first 30 weeks (Part A) or up to 84 weeks in relation to Protocol Amendment #5



  Baseline Characteristics
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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.
All patients from the Full Analysis Set (FAS) which includes those patients in the treated set who had a baseline HbA1c value and at least one on-treatment HbA1c value.

Reporting Groups
  Description
Pio15/Pio30 Participants treated with pioglitazone 15mg for 30 weeks followed by pioglitazone 30mg for up to 54 weeks.
Pio30/Pio30 Participants treated with pioglitazone 30mg for 30 weeks followed by pioglitazone 30mg for up to 54 weeks.
Pio45/Pio45 Participants treated with pioglitazone 30 mg for 6 weeks and then were titrated up to pioglitazone 45mg for 24 weeks followed by pioglitazone 45mg for up to 54 weeks.
Lina5/Lina5 Participants treated with linagliptin 5mg + pioglitazone 15mg fixed dose combination (FDC) for 30 weeks followed by linagliptin 5mg + pioglitazone 30mg FDC for up to 54 weeks.
Lina5Pio15/Lina5Pio30 Participants treated with linagliptin 5mg + pioglitazone 15mg fixed dose combination (FDC) for 30 weeks followed by a blinded trial period on linagliptin 5mg + pioglitazone 30mg FDC
Lina5Pio30/Lina5Pio30 Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for 30 weeks followed by linagliptin 5mg + pioglitazone 30mg FDC for up to 54 weeks.
Lina5Pio45/Lina5Pio45 Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for 6 weeks and linagliptin 5mg + pioglitazone 45mg FDC for 24 weeks followed by linagliptin 5mg + pioglitazone 45mg FDC for up to 54 weeks.
Total Total of all reporting groups

Baseline Measures
    Pio15/Pio30     Pio30/Pio30     Pio45/Pio45     Lina5/Lina5     Lina5Pio15/Lina5Pio30     Lina5Pio30/Lina5Pio30     Lina5Pio45/Lina5Pio45     Total  
Number of Participants  
[units: participants]
  124     134     134     130     120     125     126     893  
Age  
[units: years]
Mean ± Standard Deviation
  56.4  ± 10.4     57.2  ± 11.1     56.5  ± 11.1     56.3  ± 10.1     57.1  ± 10.2     56.4  ± 10.0     60.1  ± 10.2     57.1  ± 10.5  
Gender  
[units: participants]
               
Female     57     64     66     51     54     61     57     410  
Male     67     70     68     79     66     64     69     483  
Baseline HbA1c  
[units: percent]
Mean ± Standard Deviation
  8.33  ± 0.93     7.99  ± 0.85     8.12  ± 0.87     8.01  ± 0.88     8.13  ± 0.94     8.17  ± 1.07     8.01  ± 0.81     8.11  ± 0.91  
Baseline fasting plasma glucose (FPG)  
[units: mg/dL]
Mean ± Standard Deviation
  171.3  ± 39.3     165.8  ± 40.0     167.5  ± 37.9     161.4  ± 38.1     167.3  ± 39.5     168.8  ± 46.8     162.3  ± 36.8     166.3  ± 39.9  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in HbA1c After 30 Weeks of Treatment.   [ Time Frame: Baseline and 30 weeks ]

2.  Secondary:   Occurrence of Cumulative Treat to Target Efficacy Response, of HbA1c Under Treatment of < 7.0% After 30 Weeks of Treatment   [ Time Frame: Baseline and 30 weeks ]

3.  Secondary:   Occurrence of Cumulative Treat to Target Efficacy Response, of HbA1c Under Treatment of < 6.5% After 30 Weeks of Treatment   [ Time Frame: Baseline and 30 weeks ]

4.  Secondary:   Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 30 Weeks of Treatment)   [ Time Frame: Baseline and 30 weeks ]

5.  Secondary:   HbA1c Change From Baseline by Visit Over Time   [ Time Frame: Baseline, week 6, week 12, week 18, week 24, week 30 ]
  Hide Outcome Measure 5

Measure Type Secondary
Measure Title HbA1c Change From Baseline by Visit Over Time
Measure Description

HbA1c is measured as a percentage. The change from baseline is the HbA1c over time minus the baseline HbA1c. The model includes fixed effects for treatment, continuous baseline HbA1c, prior andi-diabetic medication, country, visit and treatment.

by visit interaction.

Time Frame Baseline, week 6, week 12, week 18, week 24, week 30  
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.
FAS (observed cases)

Reporting Groups
  Description
Pio15 Participants treated with pioglitazone 15mg monotherapy for the first 30 weeks
Pio30 Participants treated with pioglitazone 30mg monotherapy for the first 30 weeks
Pio45 Participants treated with pioglitazone 30mg monotherapy for 6 weeks and were titrated to pioglitazone 45mg monotherapy for the next 24 weeks.
Lina5 Participants treated with linagliptin 5mg once daily for the first 30 weeks
Lina5Pio15 Participants treated with linagliptin 5mg + pioglitazone 15mg fixed dose combination (FDC) for the first 30 weeks
Lina5Pio30 Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 30 weeks
Lina5Pio45 Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 6 weeks and were titrated to linagliptin 5mg + pioglitazone 45mg for the next 24 weeks.

Measured Values
    Pio15     Pio30     Pio45     Lina5     Lina5Pio15     Lina5Pio30     Lina5Pio45  
Number of Participants Analyzed  
[units: participants]
  124     134     134     130     120     125     126  
HbA1c Change From Baseline by Visit Over Time  
[units: percent]
Mean ± Standard Error
             
Change to week 6 (N=121,133,133,130,119,124,125)     -0.22  ± 0.06     -0.16  ± 0.06     -0.20  ± 0.06     -0.23  ± 0.06     -0.43  ± 0.06     -0.47  ± -0.06     -0.62  ± 0.06  
Change to week 12 (N=112,124,127,122,111,117,120)     -0.47  ± 0.08     -0.43  ± 0.07     -0.59  ± 0.07     -0.36  ± 0.08     -0.71  ± 0.08     -0.92  ± 0.08     -1.01  ± 0.08  
Change to week 18 (N=101,121,122,112,104,104,115)     -0.63  ± 0.09     -0.58  ± 0.08     -0.82  ± 0.08     -0.39  ± 0.08     -0.81  ± 0.09     -1.07  ± 0.09     -1.22  ± 0.09  
Change to week 24 (N=91,108,110,95,92,96,109)     -0.75  ± 0.09     -0.67  ± 0.09     -0.87  ± 0.09     -0.39  ± 0.09     -0.84  ± 0.09     -1.10  ± 0.09     -1.23  ± 0.09  
Change to week 30 (N=78,93,91,79,86,87,97)     -0.77  ± 0.09     -0.73  ± 0.08     -0.94  ± 0.09     -0.37  ± 0.09     -0.87  ± 0.09     -1.09  ± 0.09     -1.27  ± 0.09  

No statistical analysis provided for HbA1c Change From Baseline by Visit Over Time



6.  Secondary:   Fasting Plasma Glucose (FPG) Change From Baseline After 30 Weeks of Treatment   [ Time Frame: Baseline and 30 weeks ]

7.  Secondary:   Fasting Plasma Glucose (FPG) Change From Baseline by Visit Over Time   [ Time Frame: Baseline, week 6, week 12, week 18, week 24, week 30 ]

8.  Secondary:   Two-hour Postprandial Glucose (2hPPG) Change From Baseline at Week 30 by Meal Tolerance Test (MTT)   [ Time Frame: Baseline and 30 weeks ]

9.  Secondary:   Time to First Use of Rescue Therapy   [ Time Frame: 30 weeks ]

10.  Secondary:   Incidence of Rescue Therapy During the First 30 Weeks of Treatment   [ Time Frame: 30 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
The study (Part B treatment only) was stopped early by protocol amendment #5, although Part A (time frame for all efficacy outcomes) proceeded to completion


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


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
ClinicalTrials.gov Identifier: NCT01183013     History of Changes
Other Study ID Numbers: 1264.3, 2008-008127-15
Study First Received: August 16, 2010
Results First Received: March 12, 2014
Last Updated: June 3, 2014
Health Authority: Estonia: The State Agency of Medicine
Germany: Federal Institute for Drugs and Medical Devices
Latvia: State Agency of Medicines
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration