Diabetes Mellitus, Type 2Phase 3NCT00819091

Randomized, Double-blind (db), Placebo-controlled 18 Week Study of Linagliptin (BI 1356) in Type 2 Diabetic Patients With Insufficient Glycaemic Control on a Sulfonylurea Drug

A Phase 3 study testing BI 1356 in people with Diabetes Mellitus, Type 2, run by Boehringer Ingelheim at 45 sites in 7 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

Efficacy and safety of BI 1356 compared to placebo in patients with type 2 diabetes who have insufficient glycaemic control despite treatment with a sulfonylurea drug. Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Diabetes Mellitus, Type 2
What is being tested?: BI 1356
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 245 participants
Where: 45 sitesin 7 countries
Study dates: Dec 2008to Jan 2010
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 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients between 18 and 80 years old with type 2 diabetes and insufficient glycemic control [glycosylated hemoglobin (HbA1c 7% to 10%)] despite therapy with a sulfonylurea drug

Who cannot join

Myocardial infarction,stroke or transient ischaemic attack in last 6 months Treatment with rosiglitazone, pioglitazone, GLP-1 analogues, insulin or anti-obesity drugs in the past 3 months Impaired hepatic function Severe renal impairment Current treatment with systemic steroids Change in thyroid hormone dosage Hereditary galactose intolerance

Trial locations and contacts

45 sites in 7 countries.

Country

City, postcode or hospital

45 sites in 7 countries

United States13 sites

1218.35.10018 Boehringer Ingelheim Investigational Site
Asheville, North Carolina
1218.35.10002 Boehringer Ingelheim Investigational Site
Birmingham, Alabama
1218.35.10013 Boehringer Ingelheim Investigational Site
Chicago, Illinois
1218.35.10004 Boehringer Ingelheim Investigational Site
Cincinnati, Ohio
1218.35.10009 Boehringer Ingelheim Investigational Site
Dallas, Texas
1218.35.10015 Boehringer Ingelheim Investigational Site
Flint, Michigan
1218.35.10017 Boehringer Ingelheim Investigational Site
Fort Lauderdale, Florida
1218.35.10021 Boehringer Ingelheim Investigational Site
Fort Lauderdale, Florida
1218.35.10020 Boehringer Ingelheim Investigational Site
Greenville, South Carolina
1218.35.10001 Boehringer Ingelheim Investigational Site
Los Angeles, California
1218.35.10016 Boehringer Ingelheim Investigational Site
National City, California
1218.35.10005 Boehringer Ingelheim Investigational Site
Portland, Oregon
1218.35.10019 Boehringer Ingelheim Investigational Site
Sugar Land, Texas

Other trials in United States

India8 sites

1218.35.91003 Boehringer Ingelheim Investigational Site
Aligarh, Uttar Pradesh
1218.35.91007 Boehringer Ingelheim Investigational Site
Aminjikarai, Tamilnadu
1218.35.91001 Boehringer Ingelheim Investigational Site
Bangalore, Karnataka
1218.35.91004 Boehringer Ingelheim Investigational Site
Bangalore, Karnataka
1218.35.91002 Boehringer Ingelheim Investigational Site
Indore
1218.35.91008 Boehringer Ingelheim Investigational Site
Mumbai, Maharastra
1218.35.91005 Boehringer Ingelheim Investigational Site
Nagpur, Maharashtra
1218.35.91006 Boehringer Ingelheim Investigational Site
Pune, Maharastra

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Russia7 sites

1218.35.70008 Boehringer Ingelheim Investigational Site
Arkhangelsk
1218.35.70001 Boehringer Ingelheim Investigational Site
Saint Petersburg
1218.35.70002 Boehringer Ingelheim Investigational Site
Saint Petersburg
1218.35.70003 Boehringer Ingelheim Investigational Site
Saint Petersburg
1218.35.70006 Boehringer Ingelheim Investigational Site
Saint Petersburg
1218.35.70009 Boehringer Ingelheim Investigational Site
Saint Petersburg
1218.35.70007 Boehringer Ingelheim Investigational Site
Yaroslavl

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Hungary5 sites

1218.35.36001 Boehringer Ingelheim Investigational Site
Budapest
1218.35.36002 Boehringer Ingelheim Investigational Site
Budapest
1218.35.36004 Boehringer Ingelheim Investigational Site
Budapest
1218.35.36005 Boehringer Ingelheim Investigational Site
Budapest
1218.35.36003 Boehringer Ingelheim Investigational Site
Debrecen

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Poland5 sites

1218.35.48002 Boehringer Ingelheim Investigational Site
Bialystok
1218.35.48004 Boehringer Ingelheim Investigational Site
Lublin
1218.35.48003 Boehringer Ingelheim Investigational Site
Poznan
1218.35.48001 Boehringer Ingelheim Investigational Site
Rzeszów
1218.35.48005 Boehringer Ingelheim Investigational Site
Wroclaw

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Argentina4 sites

1218.35.54003 Boehringer Ingelheim Investigational Site
Capital Federal
1218.35.54005 Boehringer Ingelheim Investigational Site
Corrientes
1218.35.54001 Boehringer Ingelheim Investigational Site
Mar del Plata
1218.35.54006 Boehringer Ingelheim Investigational Site
Parque Velez Sarfield

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Japan3 sites

1218.35.81003 Boehringer Ingelheim Investigational Site
Osaka, Osaka
1218.35.81001 Boehringer Ingelheim Investigational Site
Shinjyuku-ku,Tokyo
1218.35.81002 Boehringer Ingelheim Investigational Site
Suita, Osaka,

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About this study

Official title: A Randomized, Double-blind, Placebo-controlled Parallel Group Efficacy and Safety Study of BI 1356 (5 mg Administered Orally Once Daily) Over 18 Weeks in Type 2 Diabetic Patients With Insufficient Glycaemic Control (HbA1c 7.0-10%) Despite Background Therapy With a Sulfonylurea Drug.

Efficacy and safety of BI 1356 compared to placebo in patients with type 2 diabetes who have insufficient glycaemic control despite treatment with a sulfonylurea drug.

Conditions: Diabetes Mellitus, Type 2
Being tested: BI 1356, Placebo
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.

BI 1356Drug
5mg orally (po) tablet qd
PlaceboDrug
Placebo matching BI 1356 5mg one tablet daily

Study groups in NCT00819091
Study group	Role	What they receive
BI 1356	Active comparator	5 mg orally (po) once daily Receives: Drug: BI 1356
Placebo	Placebo comparator	one tablet 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) at Week 18
HbA1c is measured as a percent. The change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c and previous anti-diabetic medication.
Measured: Baseline, week 18

Secondary outcomes (9)

Change From Baseline in Fasting Plasma Glucose at Week 18
Change from baseline reflects the Week 18 FPG minus the Week 0 FPG. Means are adjusted for baseline FPG and previous anti-diabetic medication.
Measured: Baseline, week 18
Percentage of Patients With Absolute Efficacy Response (HbA1c < 7%) at Week 18
An absolute efficacy response is defined as HbA1c < 7.0% at 18 weeks. A non-response is defined as HbA1c >= 7.0% at 18 weeks.
Measured: week 18
Percentage of Patients With Absolute Efficacy Response (HbA1c < 6.5%) at Week 18
An absolute efficacy response is defined as HbA1c < 6.5% at 18 weeks. A non-response is defined as HbA1c >= 6.5% at 18 weeks.
Measured: week 18
Percentage of Patients With HbA1c Lowering by at Least 0.5% From Baseline at Week 18
An efficacy response is defined as HbA1c lowered by 0.5% or more at 18 weeks. A non-response is defined as HbA1c not lowered by 0.5% or more at 18 weeks.
Measured: Baseline, week 18
Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 6
HbA1c is measured as a percent. The change from baseline reflects the Week 6 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c and previous anti-diabetic medication.
Measured: Baseline, week 6
Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 12
HbA1c is measured as a percent. The change from baseline reflects the Week 12 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c and previous anti-diabetic medication.
Measured: Baseline, week 12
Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 18
HbA1c is measured as a percent. The change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c and previous anti-diabetic medication.
Measured: Baseline, week 18
Change From Baseline in Fasting Plasma Glucose at Week 6
Change from baseline reflects the Week 6 FPG minus the Week 0 FPG. Means are adjusted for baseline FPG and previous anti-diabetic medication.
Measured: Baseline, week 6
Change From Baseline in Fasting Plasma Glucose at Week 12
Change from baseline reflects the Week 12 FPG minus the Week 0 FPG. Means are adjusted for baseline FPG and previous anti-diabetic medication.
Measured: Baseline, week 12

Timeline

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

Dec 2008Jan 2010

First posted8 Jan 2009 (estimated)
Study startDec 2008
Primary completionJan 2010

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 (3)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: 245 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00819091
Sponsor's protocol ID: 1218.35
Other IDs: 2008-003118-86, 2008
Status last verified: Dec 2013
First submitted: 7 Jan 2009
Last updated: 27 Jun 2014
Results posted: Yes, on ClinicalTrials.gov

Publications

McGill JB, Barnett AH, Lewin AJ, Patel S, Neubacher D, von Eynatten M, Woerle HJ. Linagliptin added to sulphonylurea in uncontrolled type 2 diabetes patients with moderate-to-severe renal impairment. Diab Vasc Dis Res. 2014 Jan;11(1):34-40. doi: 10.1177/1479164113507068. Epub 2013 Oct 29.
PubMed 24169807
Lewin AJ, Arvay L, Liu D, Patel S, von Eynatten M, Woerle HJ. Efficacy and tolerability of linagliptin added to a sulfonylurea regimen in patients with inadequately controlled type 2 diabetes mellitus: an 18-week, multicenter, randomized, double-blind, placebo-controlled trial. Clin Ther. 2012 Sep;34(9):1909-19.e15. doi: 10.1016/j.clinthera.2012.07.008. Epub 2012 Aug 29.
PubMed 22939034
Johansen OE, Neubacher D, von Eynatten M, Patel S, Woerle HJ. Cardiovascular safety with linagliptin in patients with type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a phase 3 programme. Cardiovasc Diabetol. 2012 Jan 10;11:3. doi: 10.1186/1475-2840-11-3.
PubMed 22234149

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 27 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-blind, Placebo-controlled Parallel Group Efficacy and Safety Study of BI 1356 (5 mg Administered Orally Once Daily) Over 18 Weeks in Type 2 Diabetic Patients With Insufficient Glycaemic Control (HbA1c 7.0-10%) Despite Background Therapy With a Sulfonylurea Drug.
ClinicalTrials.gov ID: NCT00819091
Acronym / sponsor ID: 1218.35
Conditions: Diabetes Mellitus, Type 2
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 245 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: Dec 2008
Primary completion: Jan 2010 (actual)
First posted: 8 Jan 2009 (estimated)
Results: Posted 1 Aug 2011

Clinical summary

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

Efficacy and safety of BI 1356 compared to placebo in patients with type 2 diabetes who have insufficient glycaemic control despite treatment with a sulfonylurea drug.

Study design

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

Arm	Type	Receives
BI 1356	Active comparator	Drug: BI 13565 mg orally (po) once daily
Placebo	Placebo comparator	Drug: Placeboone tablet once daily

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

Patients between 18 and 80 years old with type 2 diabetes and insufficient glycemic control [glycosylated hemoglobin (HbA1c 7% to 10%)] despite therapy with a sulfonylurea drug

Key exclusion criteria (1 listed)

Myocardial infarction,stroke or transient ischaemic attack in last 6 months Treatment with rosiglitazone, pioglitazone, GLP-1 analogues, insulin or anti-obesity drugs in the past 3 months Impaired hepatic function Severe renal impairment Current treatment with systemic steroids Change in thyroid hormone dosage Hereditary galactose intolerance

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
BI 13565mg orally (po) tablet qd	Drug	BI 1356
PlaceboPlacebo matching BI 1356 5mg one tablet daily	Drug	Placebo

Primary outcome

Change From Baseline in HbA1c (Glycosylated Hemoglobin) at Week 18
Time frame: Baseline, week 18
HbA1c is measured as a percent. The change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c and previous anti-diabetic medication.

9 secondary outcomes

Change From Baseline in Fasting Plasma Glucose at Week 18
Time frame: Baseline, week 18
Percentage of Patients With Absolute Efficacy Response (HbA1c < 7%) at Week 18
Time frame: week 18
Percentage of Patients With Absolute Efficacy Response (HbA1c < 6.5%) at Week 18
Time frame: week 18
Percentage of Patients With HbA1c Lowering by at Least 0.5% From Baseline at Week 18
Time frame: Baseline, week 18
Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 6
Time frame: Baseline, week 6
Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 12
Time frame: Baseline, week 12
Mixed Model Repeated Measurements Analysis of Change From Baseline in HbA1c at Week 18
Time frame: Baseline, week 18
Change From Baseline in Fasting Plasma Glucose at Week 6
Time frame: Baseline, week 6
Change From Baseline in Fasting Plasma Glucose at Week 12
Time frame: Baseline, week 12

Results and safety

Results posted to the registry on 1 Aug 2011, 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	84	77
Linagliptin (BI 1356) 5.0 mg	161	151

Primary outcome: Change From Baseline in HbA1c (Glycosylated Hemoglobin) at Week 18

Time frame: Baseline, week 18. Least squares mean (Standard Error). Unit: percent

Measure	Placebo n = 82	Linagliptin 5.0 mg n = 158
Value	-0.07 (0.10)	-0.54 (0.07)

Placebo vs Linagliptin 5.0 mg: Least Squares Mean Difference: -0.47 (95% CI -0.70 to -0.24), p < 0.0001, ANCOVA

Population analysed: Full Analysis Set includes all randomized patients with baseline and on-treatment value of HbA1c. Last observation carried forward (LOCF) was used as the imputation rule.

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: From day of first dose until 7 days after last dose. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	1 of 84 (1.2%)	14 of 84 (16.7%)	Not reported
Linagliptin 5.0 mg	5 of 161 (3.1%)	14 of 161 (8.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 24169807McGill JB, Barnett AH, Lewin AJ, Patel S, Neubacher D, von Eynatten M, Woerle HJ. Linagliptin added to sulphonylurea in uncontrolled type 2 diabetes patients with moderate-to-severe renal impairment. Diab Vasc Dis Res. 2014 Jan;11(1):34-40. doi: 10.1177/1479164113507068. Epub 2013 Oct 29.
Derived from this study: PubMed 22939034Lewin AJ, Arvay L, Liu D, Patel S, von Eynatten M, Woerle HJ. Efficacy and tolerability of linagliptin added to a sulfonylurea regimen in patients with inadequately controlled type 2 diabetes mellitus: an 18-week, multicenter, randomized, double-blind, placebo-controlled trial. Clin Ther. 2012 Sep;34(9):1909-19.e15. doi: 10.1016/j.clinthera.2012.07.008. Epub 2012 Aug 29.
Derived from this study: PubMed 22234149Johansen OE, Neubacher D, von Eynatten M, Patel S, Woerle HJ. Cardiovascular safety with linagliptin in patients with type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a phase 3 programme. Cardiovasc Diabetol. 2012 Jan 10;11:3. doi: 10.1186/1475-2840-11-3.
Related InfoLink provided by the sponsor.
Related InfoLink provided by the sponsor.

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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

45 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing BI 1356 in people with Diabetes Mellitus, Type 2, run by Boehringer Ingelheim at 45 sites in 7 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 1 inclusion and 1 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 27 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 45 sites in United States, India, Russia, Hungary, Poland and 2 more countries. 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 1 Aug 2011). 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) at Week 18 (time frame: Baseline, week 18). 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 NCT00819091, which also lists 3 linked publications.

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 27 Jun 2014.