Linagliptin as Add on Therapy to Empagliflozin 10 mg or 25 mg With Background Metformin in Patient With Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01778049
First received: January 24, 2013
Last updated: March 4, 2016
Last verified: March 2016
  Purpose
The objective of the study is to investigate the efficacy, safety and tolerability of linagliptin 5 mg qd compared to placebo given for 24 weeks in inadequately controlled T2DM patients on empagliflozin 10 mg or 25 mg and maximum tolerated dose of metformin. The primary objective of efficacy evaluation is planned after 24 weeks of treatment. The study is designed to show superiority of the combination of empagliflozin and linagliptin over empagliflozin alone.

Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: BI 10773
Drug: BI 10773 Placebo
Drug: BI 10773 / BI 1356
Drug: BI 10773 / BI 1356 Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Double-blind, Parallel Group Study to Evaluate the Efficacy and Safety of Linagliptin 5 mg Compared to Placebo, Administered as Oral Fixed Dose Combination With Empagliflozin 10 mg or 25 mg for 24 Weeks, in Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control After 16 Weeks of Treatment With Empagliflozin 10 mg or 25 mg on Metformin Background Therapy

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Change From Baseline of HbA1c After 24 Weeks of Treatment. [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]

    Change from baseline in Glycated haemoglobin (HbA1c) [%] after 24 weeks of treatment with double-blind trial medication, i.e. HbA1c change from baseline at Week 24. The term "baseline" was not used to refer to measurements prior to the administration of open-label medication. Such measurements were referred to as "pre-treatment". Analyses of change from pre-treatment used the last value before first administration of open-label medication as point of reference.

    Observed Case (OC): This method analyse only available data that were observed while patients were on treatment, i.e., excluding the missing data. All values measured after rescue medication taken were set to missing. Full Analysis Set (FAS): Includes all patients in the Treated set who had a baseline HbA1c assessment and at least 1 on-treatment HbA1c assessment during the double-blind part of the trial.



Secondary Outcome Measures:
  • Fasting Plasma Glucose (FPG) Change From Baseline at 24 Weeks. [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline FPG (mmol/L) after 24 weeks of treatment with double-blind trial medication, i.e. FPG change from baseline at Week 24.


Enrollment: 708
Study Start Date: January 2013
Study Completion Date: March 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Empagliflozin 10 mg dose
Empagliflozin open label treatment period
Drug: BI 10773
Empagliflozin active
Experimental: Placebo add on 10 mg dose
Empagliflozin / Linagliptin 10/5 mg Dose FDC placebo add on run-in
Drug: BI 10773 / BI 1356 Placebo
Empagliflozin / Linagliptin 10/5 mg Dose placebo FDC
Drug: BI 10773
Empagliflozin active
Experimental: Empagliflozin/Linagliptin 25/5 mg Dose
Empagliflozin / Linagliptin 25/5 mg Dose FDC active
Drug: BI 10773 / BI 1356
Empagliflozin / Linagliptin 25/5 mg Dose FDC active
Drug: BI 10773 Placebo
Empagliflozin placebo
Experimental: Empagliflozin/Linagliptin 10/5 mg Dose.
Empagliflozin / Linagliptin 10/5 mg Dose FDC placebo
Drug: BI 10773 / BI 1356 Placebo
Empagliflozin / Linagliptin 10/5 mg Dose FDC placebo
Drug: BI 10773
Empagliflozin active
Experimental: Empagliflozin/Linagliptin 10/5 mg Dose
Empagliflozin / Linagliptin 10/5 mg Dose FDC active
Drug: BI 10773 Placebo
Empagliflozin placebo
Drug: BI 10773 / BI 1356
Empagliflozin / Linagliptin 10/5 mg Dose FDC active
Experimental: Empagliflozin 25 mg dose
Empagliflozin open label treatment period
Drug: BI 10773
Empagliflozin active
Experimental: Empagliflozin/Linagliptin 25/5 mg Dose.
Empagliflozin / Linagliptin 25/5 mg Dose FDC placebo
Drug: BI 10773
Empagliflozin active
Drug: BI 10773 / BI 1356 Placebo
Empagliflozin / Linagliptin 25/5 mg Dose FDC placebo
Experimental: Placebo add on 25 mg dose
Empagliflozin / Linagliptin 25/5 mg Dose FDC placebo add on run-in
Drug: BI 10773
Empagliflozin active
Drug: BI 10773 / BI 1356 Placebo
Empagliflozin / Linagliptin 25/5 mg Dose FDC placebo

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Signed and dated ICF (Informed Consent Form)
  2. Male or female on diet and exercise regime and on stable background metformin > or equal to 1500 mg or maximun dose according to local label
  3. HBA1c (Glicoslated Hemoglobin) > or equal to 8% and < or equal to 10.5 % at Visit 1
  4. HbA1c > or equal to 7 and < or equal to 10.5 at Visit 4
  5. Age > or equal to 18 years
  6. BMI (Body Mass Index) < or equal to 45

Exclusion criteria:

  1. Uncontrolled hyperglycemia during open label period and placebo add on "run-in" period
  2. Use of any other antidiabetic
  3. Renal function below 60 ml/min/1.73 m2
  4. Antiobesity drugs or aggresive diets
  5. Gastorintestinal surgeries
  6. Current systemic steroids or uncontrolled endocrine disorders other than Diabetes Type 2
  7. Acute coronary syndrome and stroke within 3 months of informed consent
  8. Known allergies to DPP-IV (Dypeptidil Peptidase IV) or SGLT-2 (Sodium Glucose Transporter 2) inhibitors
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01778049

  Show 114 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Eli Lilly and Company
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01778049     History of Changes
Other Study ID Numbers: 1275.10  2012-002271-34 
Study First Received: January 24, 2013
Results First Received: March 4, 2016
Last Updated: March 4, 2016
Health Authority: Argentina: Admin Nacional de Medicamentos, Alimentos Tecnologia Medica
Australia: Dept of Health and Ageing Therapeutic Goods Admin
Canada: Canadian Institutes of Health Research
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ethics Committee
Portugal: National Pharmacy and Medicines Institute
Russia: Pharmacological Committee, Ministry of Health
Spain: Spanish Agency of Medicines
Ukraine: State Pharmacological Center - Ministry of Health
United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Empagliflozin
Metformin
Linagliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2016