Clinical trial NCT00749190: BI 10773 add-on to Metformin in Patients With Type 2 Diabetes
Official title: A Phase II, Randomized, Parallel Group Safety, Efficacy, and Pharmacokinetics Study of BI 10773 (1 mg, 5 mg, 10 mg, 25 mg, and 50 mg) Administered Orally Once Daily Over 12 Weeks Compared Double Blind to Placebo With an Additional Open-label Sitagliptin Arm in Type 2 Diabetic Patients With Insufficient Glycemic Control Despite Metformin Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2008-09-09
Enrollment: 495
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the current study is to investigate the efficacy, safety and pharmacokinetics of five doses of BI 10773 compared to placebo given for 12 weeks as add-on therapy to on going metformin therapy in patients with T2DM with insufficient glycemic control. In addition, there will be an open-label treatment arm with sitagliptin (JanuviaTM) as add-on therapy to metformin.


Eligibility criteria: Inclusion Criteria:

1. Male and female patients with a diagnosis of type 2 diabetes mellitus and previously treated with metformin alone or with metformin and one other oral antidiabetic drug
2. Stable metformin therapy of at least 1500 mg/day, or less if that is a maximum tolerated dose.
3. HbA1c at screening 6.5% to 9.0% for patients on metformin and one other antidiabetic drug, and HbA1c \>7.0% to 10% for patients on metformin only
4. HbA1c \>7.0% to 10.0% at Visit 2 (Start of Run-in)
5. Age \>=18 and \<80years
6. Body Mass Index (BMI) \<=40 kg/m2
7. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation

Exclusion Criteria:

1. Myocardial infarction, stroke or transient ischemic attack (TIA) within 6 months prior to informed consent
2. Impaired hepatic function
3. Renal insufficiency or impaired renal function
4. Diseases of the central nervous system or psychiatric disorders or clinically relevant neurological disorders that may interfere with participation in the trial
5. Chronic or clinically relevant acute infections
6. Current or chronic urogenital tract infection
7. History of clinically relevant allergy/hypersensitivity
8. Treatment with glitazones (e.g., rosiglitazone, pioglitazone), glucagon-like peptide (GLP-1) analogues, or insulin within 3 months prior to informed consent
9. Treatment with anti-obesity drugs within 3 months prior to informed consent
10. Treatment with systemic steroids or change in dosage of thyroid hormones within 6 weeks prior to informed consent
11. Alcohol abuse or drug abuse
12. Treatment with an investigational drug within 2 months prior to informed consent
13. Women of child-bearing potential who are nursing or pregnant, or who are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to periodic pregnancy testing during participation in the trial

Primary outcomes:
measure: Change From Baseline in HbA1c After 12 Weeks of Treatment
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Change of FPG From Baseline After 12 Weeks of Treatment
timeFrame: Baseline and 12 weeks
measure: Change of HbA1c From Baseline Over Time
timeFrame: Baseline and weeks 4, 8 and 12
measure: Proportion of Patients Who Achieve an HbA1c ≤7.0% After 12 Weeks of Treatment
timeFrame: Baseline and 12 weeks
measure: Proportion of Patients Who Achieve an HbA1c Lowering of at Least 0.5% After 12 Weeks of Treatment
timeFrame: Baseline and 12 weeks
measure: Change From Baseline to Week 12 in Fasting Plasma Insulin (FPI)
timeFrame: Baseline and 12 weeks
measure: Change in Homeostasis Model Assessment Index for Insulin Resistance (HOMA-IR)
timeFrame: Baseline and 12 weeks
measure: Change in Homeostasis Model Assessment Index for Beta Cell Function (HOMA-%B)
timeFrame: Baseline and 12 weeks
measure: Change of Body Weight After 12 Weeks of Treatment
timeFrame: Baseline and 12 weeks
measure: Trough Concentrations of Empagliflozin in Plasma
timeFrame: Days 28, 56 and 84
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: 1245.10.10026 Boehringer Ingelheim Investigational Site
state: California
city: Mission Viejo
country: United States
facility: 1245.10.10001 Boehringer Ingelheim Investigational Site
state: California
city: Pasadena
country: United States
facility: 1245.10.10011 Boehringer Ingelheim Investigational Site
state: California
city: Spring Valley
country: United States
facility: 1245.10.10028 Boehringer Ingelheim Investigational Site
state: California
city: Walnut Creek
country: United States
facility: 1245.10.10027 Boehringer Ingelheim Investigational Site
state: California
city: Clearwarter
country: United States
facility: 1245.10.10004 Boehringer Ingelheim Investigational Site
state: Florida
city: Melbourne
country: United States
facility: 1245.10.10021 Boehringer Ingelheim Investigational Site
state: Florida
city: Miami
country: United States
facility: 1245.10.10005 Boehringer Ingelheim Investigational Site
state: Florida
city: Miami
country: United States
facility: 1245.10.10019 Boehringer Ingelheim Investigational Site
state: Florida
city: St. Cloud
country: United States
facility: 1245.10.10024 Boehringer Ingelheim Investigational Site
state: Florida
city: Roswell
country: United States
facility: 1245.10.10014 Boehringer Ingelheim Investigational Site
state: Georgia
city: Staten Island
country: United States
facility: 1245.10.10016 Boehringer Ingelheim Investigational Site
state: New York
city: Shelby
country: United States
facility: 1245.10.10009 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Wadsworth
country: United States
facility: 1245.10.10006 Boehringer Ingelheim Investigational Site
state: Ohio
city: Norristown
country: United States
facility: 1245.10.10023 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Clemson
country: United States
facility: 1245.10.10010 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Dallas
country: United States
facility: 1245.10.10015 Boehringer Ingelheim Investigational Site
state: Texas
city: Temple
country: United States
facility: 1245.10.10012 Boehringer Ingelheim Investigational Site
state: Texas
city: Federal Way
country: United States
facility: 1245.10.10025 Boehringer Ingelheim Investigational Site
state: Washington
city: Capital Federal
country: Argentina
facility: 1245.10.54002 Boehringer Ingelheim Investigational Site
city: Capital Federal
country: Argentina
facility: 1245.10.54004 Boehringer Ingelheim Investigational Site
city: Capital Federal
country: Argentina
facility: 1245.10.54008 Boehringer Ingelheim Investigational Site
city: Mar del Plata
country: Argentina
facility: 1245.10.54006 Boehringer Ingelheim Investigational Site
city: Mendoza
country: Argentina
facility: 1245.10.54005 Boehringer Ingelheim Investigational Site
city: Graz
country: Austria
facility: 1245.10.43002 Boehringer Ingelheim Investigational Site
city: Innsbruck
country: Austria
facility: 1245.10.43004 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 1245.10.43001 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 1245.10.43003 Boehringer Ingelheim Investigational Site
city: Breclav
country: Czech Republic
facility: 1245.10.42001 Boehringer Ingelheim Investigational Site
city: Brno
country: Czech Republic
facility: 1245.10.42003 Boehringer Ingelheim Investigational Site
city: Brno
country: Czech Republic
facility: 1245.10.42005 Boehringer Ingelheim Investigational Site
city: Hodonin
country: Czech Republic
facility: 1245.10.42002 Boehringer Ingelheim Investigational Site
city: Tallin
country: Estonia
facility: 1245.10.37201 Boehringer Ingelheim Investigational Site
city: Tartu
country: Estonia
facility: 1245.10.37202 Boehringer Ingelheim Investigational Site
city: Kerava
country: Finland
facility: 1245.10.58006 Boehringer Ingelheim Investigational Site
city: Oulu
country: Finland
facility: 1245.10.58003 Boehringer Ingelheim Investigational Site
city: Tampere
country: Finland
facility: 1245.10.58004 Boehringer Ingelheim Investigational Site
city: Turku
country: Finland
facility: 1245.10.58001 Boehringer Ingelheim Investigational Site
city: Bondy Cedex
country: France
facility: 1245.10.3302A Boehringer Ingelheim Investigational Site
city: Bondy Cedex
country: France
facility: 1245.10.3302B Boehringer Ingelheim Investigational Site
city: Caen Cedex 5
country: France
facility: 1245.10.3310A Boehringer Ingelheim Investigational Site
city: Caen Cedex 5
country: France
facility: 1245.10.3310B Boehringer Ingelheim Investigational Site
city: Caen Cedex 5
country: France
facility: 1245.10.3310C Boehringer Ingelheim Investigational Site
city: Corbeil Essonnes
country: France
facility: 1245.10.3301A Boehringer Ingelheim Investigational Site
city: Corbeil Essonnes
country: France
facility: 1245.10.3301B Boehringer Ingelheim Investigational Site
city: La Rochelle Cedex 1
country: France
facility: 1245.10.3303A Boehringer Ingelheim Investigational Site
city: La Rochelle Cedex 1
country: France
facility: 1245.10.3303B Boehringer Ingelheim Investigational Site
city: La Rochelle Cedex 1
country: France
facility: 1245.10.3303C Boehringer Ingelheim Investigational Site
city: La Rochelle Cedex 1
country: France
facility: 1245.10.3303D Boehringer Ingelheim Investigational Site
city: Le Grau du Roi
country: France
facility: 1245.10.3308A Boehringer Ingelheim Investigational Site
city: Le Grau du Roi
country: France
facility: 1245.10.3308B Boehringer Ingelheim Investigational Site
city: Nanterre Cedex
country: France
facility: 1245.10.3309A Boehringer Ingelheim Investigational Site
city: Narbonne Cedex
country: France
facility: 1245.10.3306A Boehringer Ingelheim Investigational Site
city: Narbonne Cedex
country: France
facility: 1245.10.3306B Boehringer Ingelheim Investigational Site
city: Quimper
country: France
facility: 1245.10.3307A Boehringer Ingelheim Investigational Site
city: Reims Cedex
country: France
facility: 1245.10.3304A Boehringer Ingelheim Investigational Site
city: Reims Cedex
country: France
facility: 1245.10.3304B Boehringer Ingelheim Investigational Site
city: Reims Cedex
country: France
facility: 1245.10.3304C Boehringer Ingelheim Investigational Site
city: Saint Mandé
country: France
facility: 1245.10.3311A Boehringer Ingelheim Investigational Site
city: Saint Mandé
country: France
facility: 1245.10.3311B Boehringer Ingelheim Investigational Site
city: Saint Mandé
country: France
facility: 1245.10.3311C Boehringer Ingelheim Investigational Site
city: Saint Mandé
country: France
facility: 1245.10.3311D Boehringer Ingelheim Investigational Site
city: Valenciennes
country: France
facility: 1245.10.3305A Boehringer Ingelheim Investigational Site
city: Valenciennes
country: France
facility: 1245.10.3305B Boehringer Ingelheim Investigational Site
city: Valenciennes
country: France
facility: 1245.10.3305C Boehringer Ingelheim Investigational Site
city: Valenciennes
country: France
facility: 1245.10.3305D Boehringer Ingelheim Investigational Site
city: Erlangen
country: Germany
facility: 1245.10.49001 Boehringer Ingelheim Investigational Site
city: Frankfurt
country: Germany
facility: 1245.10.49003 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1245.10.49002 Boehringer Ingelheim Investigational Site
city: Rehlingen-Siersburg
country: Germany
facility: 1245.10.49004 Boehringer Ingelheim Investigational Site
city: Budapest
country: Hungary
facility: 1245.10.36001 Boehringer Ingelheim Investigational Site
city: Budapest
country: Hungary
facility: 1245.10.36003 Boehringer Ingelheim Investigational Site
city: Budapest
country: Hungary
facility: 1245.10.36004 Boehringer Ingelheim Investigational Site
city: Gyor
country: Hungary
facility: 1245.10.36005 Boehringer Ingelheim Investigational Site
city: Szombathely
country: Hungary
facility: 1245.10.36002 Boehringer Ingelheim Investigational Site
city: Daugavpils
country: Latvia
facility: 1245.10.37101 Boehringer Ingelheim Investigational Site
city: Kuldiga
country: Latvia
facility: 1245.10.37105 Boehringer Ingelheim Investigational Site
city: Ogre
country: Latvia
facility: 1245.10.37106 Boehringer Ingelheim Investigational Site
city: Riga
country: Latvia
facility: 1245.10.37103 Boehringer Ingelheim Investigational Site
city: Riga
country: Latvia
facility: 1245.10.37107 Boehringer Ingelheim Investigational Site
city: Talsi
country: Latvia
facility: 1245.10.37102 Boehringer Ingelheim Investigational Site
city: Valmiera
country: Latvia
facility: 1245.10.37104 Boehringer Ingelheim Investigational Site
city: Hamar
country: Norway
facility: 1245.10.47003 Boehringer Ingelheim Investigational Site
city: Oslo
country: Norway
facility: 1245.10.47005 Boehringer Ingelheim Investigational Site
city: Stavanger
country: Norway
facility: 1245.10.47001 Boehringer Ingelheim Investigational Site
city: Ålesund
country: Norway
facility: 1245.10.47004 Boehringer Ingelheim Investigational Site
city: Alba Iulia
country: Romania
facility: 1245.10.40001 Boehringer Ingelheim Investigational Site
city: Baia Mare Maramures
country: Romania
facility: 1245.10.40005 Boehringer Ingelheim Investigational Site
city: Brasov
country: Romania
facility: 1245.10.40003 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 1245.10.40002 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 1245.10.40007 Boehringer Ingelheim Investigational Site
city: Galati
country: Romania
facility: 1245.10.40004 Boehringer Ingelheim Investigational Site
city: Satu Mare
country: Romania
facility: 1245.10.40006 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1245.10.70001 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1245.10.70002 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1245.10.70003 Boehringer Ingelheim Investigational Site
city: Saratov
country: Russian Federation
facility: 1245.10.70007 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1245.10.70004 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1245.10.70005 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1245.10.70006 Boehringer Ingelheim Investigational Site
city: Bratislava
country: Slovakia
facility: 1245.10.62003 Boehringer Ingelheim Investigational Site
city: Nitra
country: Slovakia
facility: 1245.10.62001 Boehringer Ingelheim Investigational Site
city: Nitra
country: Slovakia
facility: 1245.10.62002 Boehringer Ingelheim Investigational Site
city: Presov
country: Slovakia
facility: 1245.10.62004 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1245.10.34002 Boehringer Ingelheim Investigational Site
city: Girona
country: Spain
facility: 1245.10.34001 Boehringer Ingelheim Investigational Site
city: L'Hospitalet de Llobregat (Barcelona)
country: Spain
facility: 1245.10.34010 Boehringer Ingelheim Investigational Site
city: Málaga
country: Spain
facility: 1245.10.34004 Boehringer Ingelheim Investigational Site
city: Palma (Mallorca)
country: Spain
facility: 1245.10.34005 Boehringer Ingelheim Investigational Site
city: Palma de Mallorca
country: Spain
facility: 1245.10.34006 Boehringer Ingelheim Investigational Site
city: Santander
country: Spain
facility: 1245.10.34008 Boehringer Ingelheim Investigational Site
city: Dnepropetrovsk
country: Ukraine
facility: 1245.10.38002 Boehringer Ingelheim Investigational Site
city: Kharkiv
country: Ukraine
facility: 1245.10.38005 Boehringer Ingelheim Investigational Site
city: Kharkov
country: Ukraine
facility: 1245.10.38004 Boehringer Ingelheim Investigational Site
city: Kiev
country: Ukraine
facility: 1245.10.38003 Boehringer Ingelheim Investigational Site
city: Vinnitsa
country: Ukraine
facility: 1245.10.38001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Tuttle KR, Levin A, Nangaku M, Kadowaki T, Agarwal R, Hauske SJ, Elsasser A, Ritter I, Steubl D, Wanner C, Wheeler DC. Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials. Diabetes Care. 2022 Jun 2;45(6):1445-1452. doi: 10.2337/dc21-2034.
citation: Riggs MM, Staab A, Seman L, MacGregor TR, Bergsma TT, Gastonguay MR, Macha S. Population pharmacokinetics of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in patients with type 2 diabetes. J Clin Pharmacol. 2013 Oct;53(10):1028-38. doi: 10.1002/jcph.147. Epub 2013 Aug 13.