Safety and Efficacy of Empagliflozin (BI 10773) and Sitagliptin Versus Placebo Over 76 Weeks in Patients With Type 2 Diabetes

Boehringer Ingelheim

Status and phase: Completed; Phase 3

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: Placebo; Drug: Sitagliptin 100mg; Drug: BI 10773

Study type: Interventional

Funder types: Industry

Identifiers

NCT01289990

2010-022718-17 (EudraCT Number)

1245.31

Details and patient eligibility

About

This study will investigate the efficacy and long term safety and tolerability of BI 10773 in type 2 diabetic patients.

Enrollment: 2,705 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients completing the entire treatment period of the preceding double-blind trial 1245.19, 1245.20 or 1245.23 with or without rescue therapy.
2. Signed and dated written informed consent by date of Visit 1 in accordance with Good Clinical Practice and local legislation.

Exclusion criteria

1. Patient who meet one or more of the withdrawal criteria of the treatment period of the previous trial 1245.19, 1245.20 or 1245.23.
2. Indication of liver disease, defined by serum levels of either alanine aminotransferase , aspartate aminotransferase, or alkaline phosphatase above 3 x upper limit of normal as determined during last visit of preceding trial.
3. Impaired renal function defined as glomerular filtration rate<30 ml/min (severe renal impairment, Modification of Diet in Renal Disease formula) as determined during last visit of preceding trial.
4. Contraindications to sitagliptin, pioglitazone, metformin or sulfonylurea according to local label, which started during trial participation in 1245.19, 1245.20 or 1245.23
5. Pre-menopausal women (last menstruation < or = 1 year prior to informed consent) who are nursing or pregnant or are of child-bearing potential and 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 submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems, oral, implantable or injectable contraceptives, sexual abstinence (if acceptable by local authorities), double barrier method and vasectomised partner.
6. Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake.
7. Participation in another trial with an investigational drug within 30 days prior to informed consent (except 1245.19, 1245.20 and 1245.23).
8. Any other clinical condition that would jeopardize patient's safety while participating in this clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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2,705 participants in 13 patient groups, including a placebo group

BI 10773 low (drug naive)

Experimental group

Description:

BI 10773 tablets once daily

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: BI 10773

Drug: BI 10773

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: BI 10773

Drug: Placebo

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

BI 10773 high (drug naive)

Experimental group

Description:

BI 10773 tablets once daily

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: BI 10773

Drug: BI 10773

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: BI 10773

Drug: Placebo

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Placebo (drug naive)

Placebo Comparator group

Description:

Placebo tablets matching BI 10773 / Sitagliptin once daily

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Sitagliptin 100mg (drug naive)

Active Comparator group

Description:

Sitagliptin once daily

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Sitagliptin 100mg

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

BI 10773 low (pioglitazone)

Experimental group

Description:

BI 10773 tablets once daily

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: BI 10773

Drug: BI 10773

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: BI 10773

Drug: Placebo

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

BI 10773 high (pioglitazone)

Experimental group

Description:

BI 10773 tablets once daily

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: BI 10773

Drug: BI 10773

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: BI 10773

Drug: Placebo

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Placebo (pioglitazone)

Placebo Comparator group

Description:

Placebo tablets matching BI 10773 once daily

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

BI 10773 low (metformin)

Experimental group

Description:

BI 10773 tablets once daily

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: BI 10773

Drug: BI 10773

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: BI 10773

Drug: Placebo

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

BI 10773 high (metformin)

Experimental group

Description:

BI 10773 tablets once daily

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: BI 10773

Drug: BI 10773

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: BI 10773

Drug: Placebo

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Placebo (metformin)

Placebo Comparator group

Description:

Placebo tablets matching BI 10773 once daily

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

BI 10773 low (metformin+sulfonylurea)

Experimental group

Description:

BI 10773 tablets once daily

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: BI 10773

Drug: BI 10773

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: BI 10773

Drug: Placebo

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

BI 10773 high (metformin+sulfonylurea)

Experimental group

Description:

BI 10773 tablets once daily

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: BI 10773

Drug: BI 10773

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: BI 10773

Drug: BI 10773

Drug: Placebo

Drug: BI 10773

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Placebo (metformin+sulfonylurea)

Placebo Comparator group

Description:

Placebo tablets matching BI 10773

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo