Trial Outcomes & Findings for MARLINA - T2D : Efficacy, Safety & Modification of Albuminuria in Type 2 Diabetes Subjects With Renal Disease With LINAgliptin (NCT NCT01792518)

Last Updated: 2017-03-06

Results Overview

Change from baseline in Glycated haemoglobin (HbA1c) \[%\] after 24 weeks of treatment with double- blind trial medication. The term "baseline" refers to the last observation before the start of any randomised trial treatment. The number of participants analysed displays the number of participants with available data at the timepoint of interest.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

360 participants

Primary outcome timeframe

Baseline and 24 weeks

Results posted on

2017-03-06

Participant Flow

360 patients were randomised and treated (Placebo: 178 patients, Linagliptin: 182 patients.)

Randomized, double-blind, placebo controlled, parallel group study to evaluate glycemic and renal efficacy of once daily administration of Linagliptin 5 milligram (mg) for 24 weeks in type 2 diabetes patients, with micro- or macroalbuminuria on top of current treatment with Angiotensin Converting Enzyme inhibitor or Angiotensin Receptor Blocker

Participant milestones

Participant milestones
Measure	Placebo Patients received 1 matching placebo tablet to Linagliptin 5 mg, administered orally, once every day for 24 weeks during the double blind treatment period.	Linagliptin 5 mg Patients received 1 tablet of Linagliptin 5 mg, administered orally, once every day for 24 weeks during the double blind treatment period.
Overall Study STARTED	178	182
Overall Study COMPLETED	170	175
Overall Study NOT COMPLETED	8	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Patients received 1 matching placebo tablet to Linagliptin 5 mg, administered orally, once every day for 24 weeks during the double blind treatment period.	Linagliptin 5 mg Patients received 1 tablet of Linagliptin 5 mg, administered orally, once every day for 24 weeks during the double blind treatment period.
Overall Study Adverse Event	3	4
Overall Study Protocol Violation	0	1
Overall Study Lost to Follow-up	3	1
Overall Study Withdrawal by Subject	2	0
Overall Study Other Reason	0	1

Baseline Characteristics

MARLINA - T2D : Efficacy, Safety & Modification of Albuminuria in Type 2 Diabetes Subjects With Renal Disease With LINAgliptin

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=178 Participants Patients received 1 matching placebo tablet to Linagliptin 5 mg, administered orally, once every day for 24 weeks during the double blind treatment period.	Linagliptin 5 mg n=182 Participants Patients received 1 tablet of Linagliptin 5 mg, administered orally, once every day for 24 weeks during the double blind treatment period.	Total n=360 Participants Total of all reporting groups
Age, Continuous	60.1 Years STANDARD_DEVIATION 9.3 • n=5 Participants	61.0 Years STANDARD_DEVIATION 10.0 • n=7 Participants	60.6 Years STANDARD_DEVIATION 9.6 • n=5 Participants
Gender Female	65 Participants n=5 Participants	66 Participants n=7 Participants	131 Participants n=5 Participants
Gender Male	113 Participants n=5 Participants	116 Participants n=7 Participants	229 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 24 weeks

Population: Full Analysis Set (FAS) - including all randomised patients who were treated with at least one dose of study drug, had a baseline HbA1c and a baseline Urinary albumin creatinine ratio (UACR), and at least one on treatment HbA1c or UACR assessment. Observed Case (OC): Values after the use of rescue medication were set to missing.

Outcome measures

Outcome measures
Measure	Placebo n=156 Participants Patients received 1 matching placebo tablet to Linagliptin 5 mg, administered orally, once every day for 24 weeks during the double blind treatment period.	Linagliptin 5 mg n=161 Participants Patients received 1 tablet of Linagliptin 5 mg, administered orally, once every day for 24 weeks during the double blind treatment period.
HbA1c Change From Baseline After 24 Weeks Double-blind Randomized Treatment	-0.03 Percentage of HbA1c Standard Error 0.06	-0.63 Percentage of HbA1c Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline and 24 weeks

The time weighted average of percentage change from baseline in UACR (mg/g creatinine) during the course of 24 weeks of treatment. The term "baseline" for UACR refers to the geometric mean of UACR values measured at Visits 2 and 3. The number of participants analysed displays the number of participants with available data at the timepoint of interest. The Least Squares Means are adjusted geometric means.

Outcome measures

Outcome measures
Measure	Placebo n=173 Participants Patients received 1 matching placebo tablet to Linagliptin 5 mg, administered orally, once every day for 24 weeks during the double blind treatment period.	Linagliptin 5 mg n=178 Participants Patients received 1 tablet of Linagliptin 5 mg, administered orally, once every day for 24 weeks during the double blind treatment period.
The Time Weighted Average of Percentage Change From Baseline in UACR During the Course of 24 Weeks of Treatment	0.9487 mg/g creatinine 95% Confidence Interval 0.06 • Interval 0.8857 to 1.0162	0.8902 mg/g creatinine 95% Confidence Interval 0.06 • Interval 0.8318 to 0.9526

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: Treated Set

The change from baseline in estimated glomerular filtration rate (eGFR) as assessed by chronic kidney disease epidemiology collaboration (CKD-EPI) equation (cystatin C) after 24 weeks of treatment. The term "baseline" refers to the last observation before the start of any randomised trial treatment. The number of participants analysed displays the number of participants with available data at the timepoint of interest. This outcome measure is a secondary safety endpoint.

Outcome measures

Outcome measures
Measure	Placebo n=156 Participants Patients received 1 matching placebo tablet to Linagliptin 5 mg, administered orally, once every day for 24 weeks during the double blind treatment period.	Linagliptin 5 mg n=162 Participants Patients received 1 tablet of Linagliptin 5 mg, administered orally, once every day for 24 weeks during the double blind treatment period.
The Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) After 24 Weeks of Treatment	-2.35 milliliter/minute/1.73 square metre Standard Error 1.92	-4.98 milliliter/minute/1.73 square metre Standard Error 1.89

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 27 other events

Deaths: 0 deaths

Linagliptin 5 mg

Serious events: 17 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=178 participants at risk Patients received 1 matching placebo tablet to Linagliptin 5 mg, administered orally, once every day for 24 weeks during the double blind treatment period.	Linagliptin 5 mg n=182 participants at risk Patients received 1 tablet of Linagliptin 5 mg, administered orally, once every day for 24 weeks during the double blind treatment period.
Infections and infestations Nasopharyngitis	5.6% 10/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	7.1% 13/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Infections and infestations Upper respiratory tract infection	5.1% 9/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	2.2% 4/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Metabolism and nutrition disorders Hypoglycaemia	5.6% 10/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	13.2% 24/182 • From first drug administration until 28 days after the last drug administration, up to 240 days

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=178 participants at risk Patients received 1 matching placebo tablet to Linagliptin 5 mg, administered orally, once every day for 24 weeks during the double blind treatment period.	Linagliptin 5 mg n=182 participants at risk Patients received 1 tablet of Linagliptin 5 mg, administered orally, once every day for 24 weeks during the double blind treatment period.
Cardiac disorders Acute myocardial infarction	0.00% 0/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.55% 1/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Cardiac disorders Cardiac failure	0.00% 0/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.55% 1/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Cardiac disorders Cardiac failure congestive	1.1% 2/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.00% 0/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Cardiac disorders Myocardial ischaemia	0.00% 0/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.55% 1/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Ear and labyrinth disorders Sudden hearing loss	0.56% 1/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.00% 0/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Ear and labyrinth disorders Vestibular disorder	0.00% 0/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	1.1% 2/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Gastrointestinal disorders Gastrointestinal fistula	0.00% 0/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.55% 1/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Gastrointestinal disorders Pancreatitis	0.56% 1/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.00% 0/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Gastrointestinal disorders Pancreatitis acute	0.56% 1/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.55% 1/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
General disorders Pyrexia	0.56% 1/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.00% 0/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Infections and infestations Abscess limb	0.00% 0/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.55% 1/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Infections and infestations Arteriovenous graft site infection	0.56% 1/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.00% 0/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Infections and infestations Cellulitis	0.00% 0/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.55% 1/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Infections and infestations Cystitis	0.00% 0/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.55% 1/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Infections and infestations Kidney infection	0.56% 1/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.00% 0/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Infections and infestations Post procedural infection	0.00% 0/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.55% 1/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Infections and infestations Pyelonephritis	0.56% 1/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.00% 0/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Infections and infestations Pyelonephritis acute	0.56% 1/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.00% 0/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Infections and infestations Septic shock	1.1% 2/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.00% 0/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.55% 1/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Injury, poisoning and procedural complications Fall	0.00% 0/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.55% 1/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Injury, poisoning and procedural complications Peripheral nerve injury	0.00% 0/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.55% 1/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Injury, poisoning and procedural complications Postpericardiotomy syndrome	0.00% 0/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.55% 1/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Investigations Lipase increased	0.56% 1/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.00% 0/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Musculoskeletal and connective tissue disorders Myositis	0.00% 0/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.55% 1/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.55% 1/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.55% 1/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Nervous system disorders Cerebral haemorrhage	0.00% 0/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.55% 1/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Nervous system disorders Seizure	0.56% 1/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.00% 0/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Nervous system disorders Transient ischaemic attack	0.56% 1/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.00% 0/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Renal and urinary disorders Acute kidney injury	0.56% 1/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.55% 1/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Renal and urinary disorders Calculus urinary	0.00% 0/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.55% 1/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.55% 1/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Vascular disorders Aortic occlusion	0.56% 1/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.00% 0/182 • From first drug administration until 28 days after the last drug administration, up to 240 days
Vascular disorders Necrosis ischaemic	0.56% 1/178 • From first drug administration until 28 days after the last drug administration, up to 240 days	0.00% 0/182 • From first drug administration until 28 days after the last drug administration, up to 240 days