Safety and Efficacy of Empagliflozin (BI 10773) in Type 1 Diabetes Mellitus Patients With or Without Renal Hyperfiltration

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01392560
• Collaborator: (none)
• Enrollment: 52
• Location: 1
• Arm: 1
• Duration (Months): 14
• Patients Per Site Per Month: 3.7

Study Details

Study Description

Brief Summary

This open-label study aims to evaluate the impact of BI 10773 treatment on glomerular filtration rate under controlled conditions of euglycaemia and hyperglycaemia in subjects with type 1 diabetes mellitus with or without renal hyperfiltration and to characterize the safety and efficacy of BI 10773 25 mg QD as add-on therapy to insulin in these subjects.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: BI 10773	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label 8-week Adjunctive-to-insulin and Renal Mechanistic Pilot Trial of BI 10773 in Type 1 Diabetes Mellitus (the ATIRMA Trial)
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BI 10773 Oral once daily	Drug: BI 10773; Oral once daily

Outcome Measures

Primary Outcome Measures

1. Change in Glomerular Filtration Rate (GFR) After 8 Weeks of Treatment With Empagliflozin Under Controlled Conditions of Euglycaemia and Hyperglycaemia [Baseline and 8 weeks]

   The primary endpoint is change in glomerular filtration rate (GFR) after 8 weeks of treatment with empagliflozin under controlled conditions of euglycaemia and hyperglycaemia

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

1. Male or female subjects 18 years of age or older diagnosed with type 1 diabetes mellitus

2. Glycated hemoglobin (HbA1C) of 6.5% to 11.0% and an estimated glomerular filtration rate (eGFR) greater or equal to 60 ml/min/1.73m² at screening

3. Subjects must be either experienced insulin pump users or be on multiple daily injections of any type of insulin

Exclusion criteria:

1. Evidence of macroalbuminuria or leukocyte positive urinalysis at screening

2. Any concomitant medication known to interfere with renin-angiotensin-aldosterone system (RAAS) activity or treatment with any other drugs to reduce blood glucose other than insulin

3. History of macrovascular disease or any other disease which would interfere with trial participation or any ongoing clinical condition that would jeopardize subject safety or study compliance based on investigator judgement

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1245.46.10001 Boehringer Ingelheim Investigational Site	Toronto	Ontario	Canada

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01392560
• Other Study ID Numbers: 1245.46
• First Posted: Jul 12, 2011
• Last Update Posted: Jun 17, 2014
• Last Verified: May 1, 2014

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Empagliflozin

Study Results

Participant Flow

Arm/Group Title	Empagliflozin (BI 10773) 25 mg
Arm/Group Description	Oral once daily Empagliflozin 25 mg: Oral once daily
Period Title: Overall Study
STARTED	52
COMPLETED	40
NOT COMPLETED	12

Baseline Characteristics

Arm/Group Title	Empagliflozin (BI 10773) 25 mg
Arm/Group Description	Oral once daily Empagliflozin 25 mg: Oral once daily
Overall Participants	42
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	24.1 (5.0)
Sex: Female, Male (Count of Participants)
Female	22 52.4%
Male	20 47.6%

Outcome Measures

1. Primary Outcome

Title	Change in Glomerular Filtration Rate (GFR) After 8 Weeks of Treatment With Empagliflozin Under Controlled Conditions of Euglycaemia and Hyperglycaemia
Description	The primary endpoint is change in glomerular filtration rate (GFR) after 8 weeks of treatment with empagliflozin under controlled conditions of euglycaemia and hyperglycaemia
Time Frame	Baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

Per protocol set for renal (PPS_RENAL) consists of all patients who were treated with study drug and had a baseline measurement and evaluable post-dosing renal data under the clamped hyperglycemia condition for the primary endpoint.

Arm/Group Title	All Patients (Empagliflozin 25 mg)	Hyperfilterers (Empagliflozin 25 mg)	Non-hyperfilterers (Empagliflozin 25 mg)
Arm/Group Description	All patients (hyperfilterers and non-hyperfilterers) Empagliflozin 25 mg: Oral once daily	Hyperfilterers Empagliflozin 25 mg: Oral once daily hyperfilterers = GFRs of ≥135 mL/min/1.73m2	Non-hyperfilterers Empagliflozin 25 mg: Oral once daily non-hyperfilterers = GFRs of ≥60 mL/min/1.73m2 to <135 mL/min/1.73m2
Measure Participants	40	27	13
Euglycaemia	-19.6 (5.6)	-33.4 (6.2)	9.0 (5.9)
Hyperglycaemia	-30.8 (6.2)	-44.5 (7.1)	-2.4 (7.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Patients (Empagliflozin 25 mg)
	Comments	Test of the difference between baseline and end of treatment under euglycaemia condition for all patients
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	Paired t-test
	Comments
Method of Estimation	Estimation Parameter	Mean change from baseline
	Estimated Value	-19.6
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.6
	Estimation Comments	Estimated value = mean of end of treatment - baseline

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	All Patients (Empagliflozin 25 mg)
	Comments	Test the difference between baseline and end of treatment under hyperglycaemia condition for all patients
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t-test
	Comments
Method of Estimation	Estimation Parameter	Mean change from baseline
	Estimated Value	-30.8
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.2
	Estimation Comments	Estimated value = mean of end of treatment - baseline

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Hyperfilterers (Empagliflozin 25 mg)
	Comments	Test of the difference between baseline and end of treatment under euglycaemia condition for hyperfilterers
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t-test
	Comments
Method of Estimation	Estimation Parameter	Change from baseline
	Estimated Value	-33.4
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.2
	Estimation Comments	Estimated value = mean of end of treatment - baseline

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Hyperfilterers (Empagliflozin 25 mg)
	Comments	Test of the difference between baseline and end of treatment under hyperglycaemia condition for hyperfilterers
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t-test
	Comments
Method of Estimation	Estimation Parameter	Mean change from baseline
	Estimated Value	-44.5
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.1
	Estimation Comments	Estimated value = mean of end of treatment - baseline

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Non-hyperfilterers (Empagliflozin 25 mg)
	Comments	Test of the difference between baseline and end of treatment under euglycaemia condition for non-hyperfilterers
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1524
	Comments
	Method	Paired t-test
	Comments
Method of Estimation	Estimation Parameter	Mean change from baseline
	Estimated Value	9.0
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.9
	Estimation Comments	Estimated value = mean of end of treatment - baseline

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Non-hyperfilterers (Empagliflozin 25 mg)
	Comments	Test of the difference between baseline and end of treatment under hyperglycaemia condition for non-filterers
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7585
	Comments
	Method	Paired t-test
	Comments
Method of Estimation	Estimation Parameter	Mean change from baseline
	Estimated Value	-2.4
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.7
	Estimation Comments	Estimated value = mean of end of treatment - baseline

Adverse Events

Time Frame	8 weeks
Adverse Event Reporting Description	All adverse events, serious and non-serious, occurring during the course of the clinical trial were to be collected, documented and reported to the sponsor by the investigator on the appropriate case reporting forms. Reporting was performed according to the specific definitions and instructions.
Arm/Group Title	Empagliflozin 25 mg
Arm/Group Description	Oral once daily Empagliflozin 25 mg: Oral once daily
All Cause Mortality
	Empagliflozin 25 mg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Empagliflozin 25 mg
	Affected / at Risk (%)	# Events
Total	3/42 (7.1%)
Infections and infestations
Gastroenteritis viral	1/42 (2.4%)
Metabolism and nutrition disorders
Diabetic ketoacidosis	2/42 (4.8%)
Other (Not Including Serious) Adverse Events
	Empagliflozin 25 mg
	Affected / at Risk (%)	# Events
Total	42/42 (100%)
Gastrointestinal disorders
Abdominal pain	5/42 (11.9%)
Dry mouth	7/42 (16.7%)
Nausea	7/42 (16.7%)
Vomiting	6/42 (14.3%)
General disorders
Thirst	31/42 (73.8%)
Infections and infestations
Genitourinary tract infection	6/42 (14.3%)
Influenza	4/42 (9.5%)
Nasopharyngitis	11/42 (26.2%)
Metabolism and nutrition disorders
Hypoglycaemia	40/42 (95.2%)
Musculoskeletal and connective tissue disorders
Back pain	4/42 (9.5%)
Nervous system disorders
Dizziness	6/42 (14.3%)
Headache	10/42 (23.8%)
Renal and urinary disorders
Pollakiuria	33/42 (78.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.