Efficacy and Safety of Empagliflozin (BI 10773) Versus Placebo and Sitagliptin Over 24 Weeks in Patients With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Phase III Randomised, Double-blind, Placebo-controlled Parallel Group Efficacy and Safety Study of BI 10773 and Sitagliptin Administered Orally Over 24 Weeks, in Drug naïve Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control Despite Diet and Exercise

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01177813
• Other study ID #: 1245.20
• Secondary ID: 2009-016243-20
• Status: Completed
• Phase: Phase 3
• First received: July 29, 2010
• Last updated: May 16, 2014
• Start date: July 2010

Study information

• Verified date: May 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal and Health ProductsCanada: Health CanadaChina: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical DevicesIndia: Drugs Controller General of IndiaIreland: Irish Medicines BoardJapan: Ministry of Health, Labor and WelfareSwitzerland: SwissmedicUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to investigate the efficacy, safety and tolerability of BI 10773 compared to placebo and sitagliptin given for 24 weeks as monotherapy in patients with T2DM with insufficient glycaemic control. For the open-label part of the study the objective is to estimate the efficacy and safety of BI 10773 when given for 24 weeks in patients with T2DM with very poor glycaemic control.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 986
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. Diagnosis of type 2 diabetes mellitus prior to informed consent;

2. Male and female patients on diet and exercise regimen who are drug-naïve;

3. HbA1c >= 7.0% and <= 10.0% at Visit 1 (screening) for randomised treatment; HbA1c > 10.0% at visit 1 (screening) for the open-label BI 10773 arm;

4. Age >= 20 (Japan); Age >= 18 (countries other than Japan);

5. BMI <= 45 kg/m2 at Visit 1 (screening);

6. Signed and dated written informed consent by date of Visit 1

Exclusion criteria:

1. Uncontrolled hyperglycaemia;

2. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or TIA within 3 months prior to informed consent;

3. Indication of liver disease, either ALT, AST, or alkaline phosphatase above 3 x ULN;

4. Impaired renal function (eGFR<50 ml/min);

5. Bariatric surgery within the past two years or other GI surgeries;

6. Medical history of cancer;

7. Contraindications to sitagliptin;

8. Blood dyscrasias or any disorders causing haemolysis or unstable red blood cell;

9. Treatment with any anti-diabetes drug within 12 weeks prior to randomisation;

10. Treatment with anti-obesity drugs or any other treatment leading to unstable body weight;

11. Current treatment with systemic steroids or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except T2DM;

12. Pre-menopausal women who are nursing or pregnant or are of child-bearing potential and not practicing an acceptable method of birth control;

13. Alcohol or drug abuse;

14. Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial;

15. Any other clinical condition that would jeopardize patients safety while participating in this clinical trial

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Placebo identical to BI10773 high dose
placebo tablets once daily
• BI 10773
BI 10773 low dose tablet once daily
• BI 10773 open label
Patients receive BI 10773 high dose tablets open label once daily
• Placebo identical to BI10773 low dose
placebo tablets once daily
• Placebo identical to BI10773 low dose
placebo tablets once daily
• Placebo identical to BI10773 high dose
placebo tablets once daily
• Placebo identical to Sitagliptin 100mg
placebo tablets once daily
• Placebo identical to Sitagliptin 100mg
placebo tablets once daily
• BI10773
BI 10773 high dose tablets once daily
• Sitagliptin
Sitagliptin tablets 100 mg once daily
• Placebo identical to Sitagliptin 100mg
placebo tablets once daily
• Placebo identical to BI10773 low dose
placebo tablets once daily
• Placebo identical to BI10773 high dose
placebo tablets once daily

Locations

Country	Name	City	State
Belgium	1245.20.32008 Boehringer Ingelheim Investigational Site	Bruxelles
Belgium	1245.20.32011 Boehringer Ingelheim Investigational Site	Bruxelles
Belgium	1245.20.32023 Boehringer Ingelheim Investigational Site	Bruxelles
Belgium	1245.20.32003 Boehringer Ingelheim Investigational Site	De Pinte
Belgium	1245.20.32015 Boehringer Ingelheim Investigational Site	Deurne
Belgium	1245.20.32016 Boehringer Ingelheim Investigational Site	Deurne
Belgium	1245.20.32025 Boehringer Ingelheim Investigational Site	Gozée
Belgium	1245.20.32022 Boehringer Ingelheim Investigational Site	Landen
Belgium	1245.20.32019 Boehringer Ingelheim Investigational Site	Leopoldsburg
Belgium	1245.20.32024 Boehringer Ingelheim Investigational Site	Linkebeek
Belgium	1245.20.32021 Boehringer Ingelheim Investigational Site	Mouscron
Belgium	1245.20.32027 Boehringer Ingelheim Investigational Site	Retie
Belgium	1245.20.32020 Boehringer Ingelheim Investigational Site	Sint-Gillis-Waas
Belgium	1245.20.32018 Boehringer Ingelheim Investigational Site	Tielt
Belgium	1245.20.32026 Boehringer Ingelheim Investigational Site	Tremelo
Canada	1245.20.20001 Boehringer Ingelheim Investigational Site	Barrie	Ontario
Canada	1245.20.20014 Boehringer Ingelheim Investigational Site	Charlottetown	Prince Edward Island
Canada	1245.20.20011 Boehringer Ingelheim Investigational Site	Chilliwack	British Columbia
Canada	1245.20.20019 Boehringer Ingelheim Investigational Site	Hamilton	Ontario
Canada	1245.20.20010 Boehringer Ingelheim Investigational Site	London	Ontario
Canada	1245.20.20017 Boehringer Ingelheim Investigational Site	London	Ontario
Canada	1245.20.20003 Boehringer Ingelheim Investigational Site	Markham	Ontario
Canada	1245.20.20012 Boehringer Ingelheim Investigational Site	Moncton	New Brunswick
Canada	1245.20.20007 Boehringer Ingelheim Investigational Site	Montague	Prince Edward Island
Canada	1245.20.20016 Boehringer Ingelheim Investigational Site	Mount Pearl	Newfoundland and Labrador
Canada	1245.20.20009 Boehringer Ingelheim Investigational Site	Newmarket	Ontario
Canada	1245.20.20013 Boehringer Ingelheim Investigational Site	Ottawa	Ontario
Canada	1245.20.20008 Boehringer Ingelheim Investigational Site	St. John's	Newfoundland and Labrador
Canada	1245.20.20005 Boehringer Ingelheim Investigational Site	Strathroy	Ontario
Canada	1245.20.20002 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1245.20.20006 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1245.20.20021 Boehringer Ingelheim Investigational Site	Trois Rivieres	Quebec
Canada	1245.20.20018 Boehringer Ingelheim Investigational Site	Victoria	British Columbia
Canada	1245.20.20015 Boehringer Ingelheim Investigational Site	Winnipeg	Manitoba
China	1245.20.86007 Boehringer Ingelheim Investigational Site	Beijing
China	1245.20.86008 Boehringer Ingelheim Investigational Site	Beijing
China	1245.20.86001 Boehringer Ingelheim Investigational Site	Guangzhou
China	1245.20.86002 Boehringer Ingelheim Investigational Site	Guangzhou
China	1245.20.86003 Boehringer Ingelheim Investigational Site	Guangzhou
China	1245.20.86012 Boehringer Ingelheim Investigational Site	Guiyang
China	1245.20.86020 Boehringer Ingelheim Investigational Site	Hangzhou
China	1245.20.86049 Boehringer Ingelheim Investigational Site	Jinan
China	1245.20.86018 Boehringer Ingelheim Investigational Site	Jingzhou
China	1245.20.86019 Boehringer Ingelheim Investigational Site	Nanchang
China	1245.20.86010 Boehringer Ingelheim Investigational Site	Nanjing
China	1245.20.86043 Boehringer Ingelheim Investigational Site	Nanjing
China	1245.20.86016 Boehringer Ingelheim Investigational Site	QingDao
China	1245.20.86004 Boehringer Ingelheim Investigational Site	Shanghai
China	1245.20.86005 Boehringer Ingelheim Investigational Site	Shanghai
China	1245.20.86006 Boehringer Ingelheim Investigational Site	Shanghai
China	1245.20.86057 Boehringer Ingelheim Investigational Site	Shenyang
China	1245.20.86017 Boehringer Ingelheim Investigational Site	Shiyan
China	1245.20.86013 Boehringer Ingelheim Investigational Site	Suzhou
China	1245.20.86015 Boehringer Ingelheim Investigational Site	Taiyuan
China	1245.20.86009 Boehringer Ingelheim Investigational Site	Wuhan
China	1245.20.86011 Boehringer Ingelheim Investigational Site	Xi'An
China	1245.20.86014 Boehringer Ingelheim Investigational Site	Xiamen
Germany	1245.20.49013 Boehringer Ingelheim Investigational Site	Dresden
Germany	1245.20.49016 Boehringer Ingelheim Investigational Site	Düsseldorf
Germany	1245.20.49015 Boehringer Ingelheim Investigational Site	Frankfurt
Germany	1245.20.49019 Boehringer Ingelheim Investigational Site	Haag
Germany	1245.20.49020 Boehringer Ingelheim Investigational Site	Hohenmölsen
Germany	1245.20.49014 Boehringer Ingelheim Investigational Site	Köthen
Germany	1245.20.49002 Boehringer Ingelheim Investigational Site	Neuwied
Germany	1245.20.49008 Boehringer Ingelheim Investigational Site	Nürnberg
Germany	1245.20.49022 Boehringer Ingelheim Investigational Site	Schauenburg
Germany	1245.20.49017 Boehringer Ingelheim Investigational Site	St. Ingbert/Oberwürzbach
Germany	1245.20.49003 Boehringer Ingelheim Investigational Site	Unterschneidheim
India	1245.20.91005 Boehringer Ingelheim Investigational Site	Bangalore
India	1245.20.91006 Boehringer Ingelheim Investigational Site	Bangalore
India	1245.20.91008 Boehringer Ingelheim Investigational Site	Bangalore
India	1245.20.91003 Boehringer Ingelheim Investigational Site	Belgaum
India	1245.20.91004 Boehringer Ingelheim Investigational Site	Chennai
India	1245.20.91009 Boehringer Ingelheim Investigational Site	Chennai
India	1245.20.91002 Boehringer Ingelheim Investigational Site	Mumbai
India	1245.20.91007 Boehringer Ingelheim Investigational Site	Mumbai, Maharastra
India	1245.20.91010 Boehringer Ingelheim Investigational Site	Nagpur
India	1245.20.91001 Boehringer Ingelheim Investigational Site	Tamil Nadu
Ireland	1245.20.35302 Boehringer Ingelheim Investigational Site	Co. Cork
Ireland	1245.20.35305 Boehringer Ingelheim Investigational Site	Co. Galway
Ireland	1245.20.35303 Boehringer Ingelheim Investigational Site	Co. Wexford
Ireland	1245.20.35304 Boehringer Ingelheim Investigational Site	Offaly
Ireland	1245.20.35306 Boehringer Ingelheim Investigational Site	Wexford
Japan	1245.20.81007 Boehringer Ingelheim Investigational Site	Chiyoda-ku, Tokyo
Japan	1245.20.81001 Boehringer Ingelheim Investigational Site	Chuo-ku, Tokyo
Japan	1245.20.81002 Boehringer Ingelheim Investigational Site	Chuo-ku, Tokyo
Japan	1245.20.81005 Boehringer Ingelheim Investigational Site	Ebetsu, Hokkaido
Japan	1245.20.81004 Boehringer Ingelheim Investigational Site	Kamakura, Kanagawa
Japan	1245.20.81003 Boehringer Ingelheim Investigational Site	Minato-ku, Tokyo
Japan	1245.20.81006 Boehringer Ingelheim Investigational Site	Shinjuku-ku, Tokyo
Japan	1245.20.81008 Boehringer Ingelheim Investigational Site	Shinjuku-ku, Tokyo
Japan	1245.20.81009 Boehringer Ingelheim Investigational Site	Suita, Osaka
Japan	1245.20.81010 Boehringer Ingelheim Investigational Site	Ube, Yamaguchi
Japan	1245.20.81012 Boehringer Ingelheim Investigational Site	Urasoe, Okinawa
Japan	1245.20.81013 Boehringer Ingelheim Investigational Site	Urasoe, Okinawa
Switzerland	1245.20.41004 Boehringer Ingelheim Investigational Site	Lugano
Switzerland	1245.20.41003 Boehringer Ingelheim Investigational Site	Rorschach
United States	1245.20.10117 Boehringer Ingelheim Investigational Site	Arkansas City	Kansas
United States	1245.20.10128 Boehringer Ingelheim Investigational Site	Avon	Indiana
United States	1245.20.10115 Boehringer Ingelheim Investigational Site	Brick	New Jersey
United States	1245.20.10129 Boehringer Ingelheim Investigational Site	Carlisle	Ohio
United States	1245.20.10154 Boehringer Ingelheim Investigational Site	Chino	California
United States	1245.20.10045 Boehringer Ingelheim Investigational Site	Cincinnati	Ohio
United States	1245.20.10119 Boehringer Ingelheim Investigational Site	Cincinnati	Ohio
United States	1245.20.10137 Boehringer Ingelheim Investigational Site	Clearwater	Florida
United States	1245.20.10080 Boehringer Ingelheim Investigational Site	Decatur	Georgia
United States	1245.20.10060 Boehringer Ingelheim Investigational Site	Fishers	Indiana
United States	1245.20.10130 Boehringer Ingelheim Investigational Site	Gallipolis	Ohio
United States	1245.20.10150 Boehringer Ingelheim Investigational Site	Hot Springs	Arkansas
United States	1245.20.10089 Boehringer Ingelheim Investigational Site	Houston	Texas
United States	1245.20.10151 Boehringer Ingelheim Investigational Site	Hurst	Texas
United States	1245.20.10065 Boehringer Ingelheim Investigational Site	Indianapolis	Indiana
United States	1245.20.10146 Boehringer Ingelheim Investigational Site	Louisville	Kentucky
United States	1245.20.10124 Boehringer Ingelheim Investigational Site	Mesa	Arizona
United States	1245.20.10006 Boehringer Ingelheim Investigational Site	Miami	Florida
United States	1245.20.10038 Boehringer Ingelheim Investigational Site	Northglenn	Colorado
United States	1245.20.10108 Boehringer Ingelheim Investigational Site	Phoenix	Arizona
United States	1245.20.10085 Boehringer Ingelheim Investigational Site	Plantation	Florida
United States	1245.20.10155 Boehringer Ingelheim Investigational Site	San Antonio	Texas
United States	1245.20.10009 Boehringer Ingelheim Investigational Site	Santa Ana	California
United States	1245.20.10078 Boehringer Ingelheim Investigational Site	Tampa	Florida
United States	1245.20.10144 Boehringer Ingelheim Investigational Site	Watertown	Massachusetts
United States	1245.20.10131 Boehringer Ingelheim Investigational Site	West Hills	California
United States	1245.20.10039 Boehringer Ingelheim Investigational Site	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Boehringer Ingelheim	Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  China,  Germany,  India,  Ireland,  Japan,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Confirmed Hypoglycaemic Adverse Events	Confirmed hypoglycaemic events refer to all hypoglycaemic events, that had a glucose value <= 70 ml/dL or where assistance was required.; Symptomatic hypoglycaemic events were to be reported as adverse events. Patients can be counted in more than one category.	From first drug intake until 7 days after last medication intake, up to 219 days	No
Primary	Change From Baseline in Glycosylated Haemoglobin (HbA1c) After 24 Weeks	The term "baseline" refers to the last observation before the start of randomised trial treatment (or of open-label treatment for the open-label arm).; In this endpoint, the "measured values" show unadjusted values, whereas the statistical analyses show adjusted values. Statistics for open-label group are descriptive.	Baseline and day 169	No
Secondary	Change From Baseline to Week 24 in Body Weight	The term "baseline" refers to the last observation before the start of randomised trial treatment (or of open-label treatment for the open-label arm).; In this endpoint, the "measured values" show unadjusted values, whereas the statistical analyses show adjusted values. Statistics for open-label group are descriptive.	Baseline and day 169	No
Secondary	Change From Baseline to Week 24 in Systolic and Diastolic Blood Pressure (SBP and DBP)	The term "baseline" refers to the last observation before the start of randomised trial treatment (or of open-label treatment for the open-label arm).; In this endpoint, the "measured values" show unadjusted values, whereas the statistical analyses show adjusted values. Statistics for open-label group are descriptive.; For blood pressure, data following changes in antihypertensive therapy is censored, in the same way that data following initiation of rescue medication is censored.	Baseline and week 24	No

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