Diabetes Mellitus, Type 2Phase 3NCT00996658

Linagliptin Versus Placebo in Type 2 Diabetic Patients With Inadequate Glycaemic Control on Metformin in Combination With Pioglitazone

A Phase 3 study testing Linagliptin in people with Diabetes Mellitus, Type 2, run by Boehringer Ingelheim at 52 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The objective of the current study is to investigate the efficacy, safety and tolerability of Linagliptin (5 mg once daily) compared to placebo given for 24 weeks as add on therapy to metformin in combination with pioglitazone in patients with type 2 diabetes mellitus with insufficient glycaemic control. Read more about this study

Who is it for?: Ages 18 to 79 years
Conditions the study is for: Diabetes Mellitus, Type 2
What is being tested?: Linagliptin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 278 participants
Where: 52 sitesin 4 countries
Study dates: Oct 2009to Mar 2012
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 79 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Diagnosis of diabetes mellitus prior to informed consent
Patients treated with metformin and pioglitazone (therapy should be unchanged for 12 weeks)
Glycosylated haemoglobin A1 >= 7.5% and <= 10%
Age between 18 and less than 80
- Body Mass index less or equal to 45

Who cannot join

Uncontrolled hyperglycaemia during run in period
Myocardial infarction, stroke or transient ischaemic accident within 3 months prior to informed consent
Impaired hepatic function
Gastric by pass surgery
Treatment with roziglitazone, GLP 1 analogues, DPP-4 inhibitors or insulin within 3 months prior to informed consent
Treatment with anti-obesity drugs
Current treatment with systemic steroids at the time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent
Premenopausal women who are nursing or pregnant or are of child-bearing potential and are not practicing an acceptable method of birth control or do not plan to continue using this method during the trial

Trial locations and contacts

52 sites in 4 countries.

Country

City, postcode or hospital

52 sites in 4 countries

United States29 sites

1218.61.01001 Boehringer Ingelheim Investigational Site
Auburn, Maine
1218.61.01024 Boehringer Ingelheim Investigational Site
Bennington, Vermont
1218.61.01016 Boehringer Ingelheim Investigational Site
Chicago, Illinois
1218.61.01018 Boehringer Ingelheim Investigational Site
Chicago, Illinois
1218.61.01005 Boehringer Ingelheim Investigational Site
Dallas, Texas
1218.61.01031 Boehringer Ingelheim Investigational Site
East Providence, Rhode Island
1218.61.01028 Boehringer Ingelheim Investigational Site
Escondido, California
1218.61.01014 Boehringer Ingelheim Investigational Site
Greenbrae, California
1218.61.01007 Boehringer Ingelheim Investigational Site
Greensboro, North Carolina
1218.61.01006 Boehringer Ingelheim Investigational Site
Houston, Texas
1218.61.01004 Boehringer Ingelheim Investigational Site
Jacksonville, North Carolina
1218.61.01048 Boehringer Ingelheim Investigational Site
Lafayette, Indiana
1218.61.01052 Boehringer Ingelheim Investigational Site
Las Vegas, Nevada
1218.61.01049 Boehringer Ingelheim Investigational Site
Lawrenceville, Georgia
1218.61.01015 Boehringer Ingelheim Investigational Site
Los Angeles, California
1218.61.01040 Boehringer Ingelheim Investigational Site
Meridian, Idaho
1218.61.01009 Boehringer Ingelheim Investigational Site
Miami, Florida
1218.61.01030 Boehringer Ingelheim Investigational Site
New York, New York
1218.61.01043 Boehringer Ingelheim Investigational Site
Olive Branch, Mississippi
1218.61.01042 Boehringer Ingelheim Investigational Site
Paramount, California
1218.61.01027 Boehringer Ingelheim Investigational Site
Perrysburg, Ohio
1218.61.01046 Boehringer Ingelheim Investigational Site
Poway, California
1218.61.01008 Boehringer Ingelheim Investigational Site
Roswell, Georgia
1218.61.01053 Boehringer Ingelheim Investigational Site
San Antonio, Texas
1218.61.01044 Boehringer Ingelheim Investigational Site
San Diego, California
1218.61.01017 Boehringer Ingelheim Investigational Site
Simpsonville, South Carolina
1218.61.01020 Boehringer Ingelheim Investigational Site
Spokane, Washington
1218.61.01003 Boehringer Ingelheim Investigational Site
Sugar Land, Texas
1218.61.01023 Boehringer Ingelheim Investigational Site
Wilmington, North Carolina

Other trials in United States

India11 sites

1218.61.91002 Boehringer Ingelheim Investigational Site
Bangalore
1218.61.91003 Boehringer Ingelheim Investigational Site
Bangalore
1218.61.91004 Boehringer Ingelheim Investigational Site
Bangalore
1218.61.91008 Boehringer Ingelheim Investigational Site
Hyderabad
1218.61.91009 Boehringer Ingelheim Investigational Site
Jaipur
1218.61.91010 Boehringer Ingelheim Investigational Site
Karnataka
1218.61.91001 Boehringer Ingelheim Investigational Site
Maharashtra
1218.61.91006 Boehringer Ingelheim Investigational Site
Maharashtra
1218.61.91011 Boehringer Ingelheim Investigational Site
Maharashtra
1218.61.91005 Boehringer Ingelheim Investigational Site
Mumbai
1218.61.91007 Boehringer Ingelheim Investigational Site
Mumbai

Other trials in India

France9 sites

1218.61.3301A Boehringer Ingelheim Investigational Site
Besançon
1218.61.3306A Boehringer Ingelheim Investigational Site
Béziers
1218.61.3311A Boehringer Ingelheim Investigational Site
Béziers
1218.61.3309A Boehringer Ingelheim Investigational Site
Bourg Des Cptes
1218.61.3310A Boehringer Ingelheim Investigational Site
Cournonterral
1218.61.3312A Boehringer Ingelheim Investigational Site
Laval
1218.61.3313A Boehringer Ingelheim Investigational Site
Louvigné-de-Bais
1218.61.3305A Boehringer Ingelheim Investigational Site
Paris
1218.61.3307A Boehringer Ingelheim Investigational Site
Paris

Other trials in France

Philippines3 sites

1218.61.63003 Boehringer Ingelheim Investigational Site
Cebu City
1218.61.63004 Boehringer Ingelheim Investigational Site
Cebu City
1218.61.63002 Boehringer Ingelheim Investigational Site
Davao City

Other trials in Philippines

About this study

Official title: A Phase III, Randomised, Double Blind, Placebo Controlled Parallel Group Efficacy and Safety Study of Linagliptin 5 mg Administered Orally Once Daily Over 24 Weeks in Type 2 Diabetic Patients With Insufficient Glycaemic Control Despite a Therapy of Metformin in Combination With Pioglitazone

Conditions: Diabetes Mellitus, Type 2
Being tested: Placebo, Linagliptin
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboDrug
Placebo matching linagliptin tablets once daily
LinagliptinDrug
Linagliptin tablets once daily

Study groups in NCT00996658
Study group	Role	What they receive
Linagliptin	Experimental	Linagliptin tablets once daily Receives: Drug: Linagliptin
Placebo	Placebo comparator	Placebo tablets once daily Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 24 Weeks
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Measured: baseline, 24 weeks

Secondary outcomes (10)

Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 6 Weeks
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Measured: baseline, 6 weeks
Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 12 Weeks
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Measured: baseline, 12 weeks
Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 18 Weeks
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Measured: baseline, 18 weeks
Occurrence of Absolute Efficacy Response (HbA1c < 7%) After 24 Weeks
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Measured: 24 weeks
Occurrence of Absolute Efficacy Response (HbA1c < 6.5%) After 24 Weeks
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Measured: 24 weeks
Occurrence of Relative Efficacy Response (Reduction in HbA1c >= 0.5%) After 24 Weeks
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin
Measured: 24 weeks
Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks
Adjusted mean change in fasting plasma glucose (FPG) from baseline at week 24
Measured: baseline, 24 weeks
Change From Baseline in Fasting Plasma Glucose (FPG) After 6 Weeks
Adjusted mean change in fasting plasma glucose (FPG) from baseline at week 6
Measured: baseline, 6 weeks
Change From Baseline in Fasting Plasma Glucose (FPG) After 12 Weeks
Adjusted mean change in fasting plasma glucose (FPG) from baseline at week 12
Measured: baseline, 12 weeks
Change From Baseline in Fasting Plasma Glucose (FPG) After 18 Weeks
Adjusted mean change in fasting plasma glucose (FPG) from baseline at week 18
Measured: baseline, 18 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2009Mar 2012

First posted16 Oct 2009 (estimated)
Study startOct 2009
Primary completionMar 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Enrolment: 278 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00996658
Sponsor's protocol ID: 1218.61
Other IDs: 2009-013289-20, 2009
Status last verified: Feb 2014
First submitted: 15 Oct 2009
Last updated: 26 Mar 2014
Results posted: Yes, on ClinicalTrials.gov

Publications

Bajaj M, Gilman R, Patel S, Kempthorne-Rawson J, Lewis-D'Agostino D, Woerle HJ. Linagliptin improved glycaemic control without weight gain or hypoglycaemia in patients with type 2 diabetes inadequately controlled by a combination of metformin and pioglitazone: a 24-week randomized, double-blind study. Diabet Med. 2014 Dec;31(12):1505-14. doi: 10.1111/dme.12495. Epub 2014 Jul 7.
PubMed 24824197

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 26 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III, Randomised, Double Blind, Placebo Controlled Parallel Group Efficacy and Safety Study of Linagliptin 5 mg Administered Orally Once Daily Over 24 Weeks in Type 2 Diabetic Patients With Insufficient Glycaemic Control Despite a Therapy of Metformin in Combination With Pioglitazone
ClinicalTrials.gov ID: NCT00996658
Acronym / sponsor ID: 1218.61
Conditions: Diabetes Mellitus, Type 2
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 278 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Collaborators: Eli Lilly and Company
Study start: Oct 2009
Primary completion: Mar 2012 (actual)
First posted: 16 Oct 2009 (estimated)
Results: Posted 26 Mar 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Number of arms: 2

Arm	Type	Receives
Linagliptin	Experimental	Drug: LinagliptinLinagliptin tablets once daily
Placebo	Placebo comparator	Drug: PlaceboPlacebo tablets once daily

Who may qualify

Ages: 18 to 79 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Diagnosis of diabetes mellitus prior to informed consent
Patients treated with metformin and pioglitazone (therapy should be unchanged for 12 weeks)
Glycosylated haemoglobin A1 >= 7.5% and <= 10%
Age between 18 and less than 80
- Body Mass index less or equal to 45

Key exclusion criteria (8 listed)

Uncontrolled hyperglycaemia during run in period
Myocardial infarction, stroke or transient ischaemic accident within 3 months prior to informed consent
Impaired hepatic function
Gastric by pass surgery
Treatment with roziglitazone, GLP 1 analogues, DPP-4 inhibitors or insulin within 3 months prior to informed consent

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PlaceboPlacebo matching linagliptin tablets once daily	Drug	Placebo
LinagliptinLinagliptin tablets once daily	Drug	Linagliptin

Primary outcome

Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 24 Weeks
Time frame: baseline, 24 weeks
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin

10 secondary outcomes

Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 6 Weeks
Time frame: baseline, 6 weeks
Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 12 Weeks
Time frame: baseline, 12 weeks
Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 18 Weeks
Time frame: baseline, 18 weeks
Occurrence of Absolute Efficacy Response (HbA1c < 7%) After 24 Weeks
Time frame: 24 weeks
Occurrence of Absolute Efficacy Response (HbA1c < 6.5%) After 24 Weeks
Time frame: 24 weeks
Occurrence of Relative Efficacy Response (Reduction in HbA1c >= 0.5%) After 24 Weeks
Time frame: 24 weeks
Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks
Time frame: baseline, 24 weeks
Change From Baseline in Fasting Plasma Glucose (FPG) After 6 Weeks
Time frame: baseline, 6 weeks
Change From Baseline in Fasting Plasma Glucose (FPG) After 12 Weeks
Time frame: baseline, 12 weeks
Change From Baseline in Fasting Plasma Glucose (FPG) After 18 Weeks
Time frame: baseline, 18 weeks

Results and safety

Results posted to the registry on 26 Mar 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo Tablet	92	76
Linagliptin 5 mg Tablet	186	165

Primary outcome: Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 24 Weeks

Time frame: baseline, 24 weeks. Least squares mean (Standard Error). Unit: Percentage

Measure	Placebo Tablet n = 89	Linagliptin 5 mg Tablet n = 179
Value	-0.27 (0.13)	-0.84 (0.11)

Placebo Tablet vs Linagliptin 5 mg Tablet: Mean Difference (Final Values): -0.57 (95% CI -0.83 to -0.31), p < 0.0001, ANCOVA

Population analysed: Full Analysis Set (FAS) includes all randomized patients who received study medication and had both a baseline HbA1c value and an on-treatment HbA1c value. Three subjects in each arm excluded for site non-compliance.

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: From drug start up to drug stop (max 24 weeks)+ 7 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo Tablet	3 of 89 (3.4%)	16 of 89 (18%)	Not reported
Linagliptin 5 mg Tablet	4 of 183 (2.2%)	31 of 183 (16.9%)	Not reported

Limitations and caveats (from the sponsor): During the conduct of this trial, pioglitazone was removed from the market in France due to safety issues, and this resulted in premature termination of a number of French patients.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 24824197Bajaj M, Gilman R, Patel S, Kempthorne-Rawson J, Lewis-D'Agostino D, Woerle HJ. Linagliptin improved glycaemic control without weight gain or hypoglycaemia in patients with type 2 diabetes inadequately controlled by a combination of metformin and pioglitazone: a 24-week randomized, double-blind study. Diabet Med. 2014 Dec;31(12):1505-14. doi: 10.1111/dme.12495. Epub 2014 Jul 7.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Boehringer Ingelheim study chair

Boehringer Ingelheim

52 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Linagliptin in people with Diabetes Mellitus, Type 2, run by Boehringer Ingelheim at 52 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 52 sites in United States, India, France, Philippines. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Mar 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 24 Weeks (time frame: baseline, 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00996658, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2014.