4 Week Treatment With Three Oral Doses of BI 10773 in Patients With Type 2 Diabetes

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of 4 Weeks Treatment With Three Oral Doses of BI 10773 as Tablets in Female and Male Patients With Type 2 Diabetes

Primary objective: safety and tolerability of BI 10773 in male and female patients with type 2 diabetes Secondary objective: pharmacokinetics and pharmacodynamics of BI 10773

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: placebo to BI 10773; Drug: BI 10773 low dose; Drug: BI 10773 medium dose; Drug: BI 10773 high dose

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • 1245.4.49003 Boehringer Ingelheim Investigational Site
  • Mainz, Germany
    • 1245.4.49002 Boehringer Ingelheim Investigational Site
  • Neuss, Germany
    • 1245.4.49001 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and postmenopausal or hysterectomised female patients with type 2 diabetes
• Age >18 and < 70 years
• BMI >18.5 and <40 kg/m2

Exclusion Criteria:

• Antidiabetic treatment with insulin or glitazones or with more than one oral hypoglycaemic agent;
• Fasted blood glucose > 240 mg/dl (>13.3 mmol/L) or a blood glucose level above 400 mg/dl (22.2 mmol/L) postprandially;
• HbA1c > 8.5 %

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: placebo to BI 10773
Experimental: BI 10773 low dose	Drug: BI 10773 low dose
Experimental: BI 10773 medium dose	Drug: BI 10773 medium dose
Experimental: BI 10773 high dose	Drug: BI 10773 high dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Drug Related Adverse Events	number of subjects with investigator-defined drug-related adverse events.	from drug administration up to 6 weeks
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinanalysis and ECG	Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinanalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events.	from drug administration up to 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of Empagliflozin	maximum concentration of the analyte in plasma after first dose (Cmax, Day 1 ) and at steady state over a uniform dosing interval (Cmax,ss, Day 28).	0:05 before drug administration and 0:15 0:30 0:45 1:00 1:30 2:00 2:30 3:00 4:00 6:00 8:00 10:00 12:00 16:00 24:00 hours(h) after drug administration on day 1 and 28
Tmax of Empagliflozin	time from last dosing to maximum concentration of the analyte in plasma after first dose (Day 1), denoted by tmax; and at steady state (Day 28), denoted by tmax,ss.	0:05 before drug administration and 0:15 0:30 0:45 1:00 1:30 2:00 2:30 3:00 4:00 6:00 8:00 10:00 12:00 16:00 24:00 h after drug administration on day 1 and 28
t1/2 of Empagliflozin	terminal half-life of the analyte in plasma after first dose (Day 1), denoted by t1/2; and at steady state (Day 28), denoted by t1/2,ss.	0:05 before drug administration and 0:15 0:30 0:45 1:00 1:30 2:00 2:30 3:00 4:00 6:00 8:00 10:00 12:00 16:00 24:00 h after drug administration on day 1 and 28
AUC0-∞ of Empagliflozin	Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) and over a uniform dosing interval τ at steady state (AUCτ,ss)	0:05 before drug administration and 0:15 0:30 0:45 1:00 1:30 2:00 2:30 3:00 4:00 6:00 8:00 10:00 12:00 16:00 24:00 h after drug administration on day 1
CL/F of Empaglifozin	apparent clearance of the analyte in plasma after first dose (CL/F) and at steady state (CL/F,ss)	0:05 before drug administration and 0:15 0:30 0:45 1:00 1:30 2:00 2:30 3:00 4:00 6:00 8:00 10:00 12:00 16:00 24:00 h after drug administration on day 1 and 28
fe0-24 of Empagliflozin	Fraction of analyte eliminated in urine from time point 0 to 24h after first dose (fe0-24) and at steady state (fe0-24,ss)	0:05 before drug administration and 0:15 0:30 0:45 1:00 1:30 2:00 2:30 3:00 4:00 6:00 8:00 10:00 12:00 16:00 24:00 h after drug administration on day 1 and 28
LI (Linearity Index).	The linearity index is defined as AUC0-τ divided by AUC0-∞ both at steady state.	0:05 before drug administration and 0:15 0:30 0:45 1:00 1:30 2:00 2:30 3:00 4:00 6:00 8:00 10:00 12:00 16:00 after drug administration on day 1 and 28
Ae0-24 of Glucose	Amount of glucose eliminated in urine over the time interval 0 to 24h on day -2, -1, 1, 27 and 28. (Urinary Glucose Excretion)	Day -2 and 27: -2 to 0, 0 to 5, 5 to 12 and 12 to 24h; Day -1 and 1: 0 to 5, 5 to 12 and 12 to 24; Day 28: 0 to 5, 5 to 12, 12 to 24, 24 to 36, 36 to 48 and 48 to 72h
Fasting Plasma Glucose (FPG)	fasting plasma glucose on day -1 (baseline) and change from baseline to day 28	in the morning of days -1 and 28
Mean Daily Glucose (MDG) Measured in Blood	change from baseline in MDG on the days 1, 7, 14, 21 and 27. Baseline is defined as day -2.	0:00, 2:30, 5:00, 7:00, 10:00, 12:00, 13:30, 24:00 h after drug administration on day -2. 0:05 h before drug administration and 2:30, 5:00, 7:00, 10:00, 12:00, 13:30, 24:00 h after drug administration on day 1, 7, 14, 21 and 27
Insulin AUEC0-5	change in AUEC0-5 from baseline on day 28. Baseline is defined as day -1.	0:00, 2:30, 5:00, 7:00, 10:00, 12:00 after drug administration on day -1. 0:05 before drug administration and 2:30, 5:00, 7:00, 10:00, 12:00 after drug administration on day 28.
Insulin Emax (Maximum Measured Effect)	change in Emax from baseline on day 28. Baseline is defined as day -1	0:00, 2:30, 5:00, 7:00, 10:00, 12:00 after drug administration on day -1. 0:05 before drug administration and 2:30, 5:00, 7:00, 10:00, 12:00 after drug administration on day 28.
Fasting Insulin	Change from baseline to the days 1, 7, 14, 21 and 28. Baseline is defined as day -1.	in the morning of days -1( baseline), 1, 7, 14, 21 and 28
Glucagon Emax (Maximum Measured Effect)	Change from baseline (day -1) in Emax on day 28.	0:00, 2:30, 5:00, 7:00, 10:00, 12:00, 24:00 h after drug administration on day -1. 0:05 before drug administration and 2:30, 5:00, 7:00, 10:00, 12:00 after drug administration on day 28.
Glucagon AUEC0-5	Change from baseline (day -1) in AUEC0-5 on day 28.	0:00, 2:30, 5:00, 7:00, 10:00, 12:00 after drug administration on day -1. 0:05 before drug administration and 2:30, 5:00, 7:00, 10:00, 12:00 after drug administration on day 28.
Fructosamine	change from baseline to days 14 and 18. Baseline is defined as day -1.	day -1 (baseline), 14 and 28
HbA1c	change from baseline on day 28. Baseline is defined as day -1.	in the morning of days -1 and 28

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Related Info
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Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): April 1, 2008
• Study Completion: December 6, 2022

Study Registration Dates

• First Submitted: November 14, 2007
• First Submitted That Met QC Criteria: November 14, 2007
• First Posted (Estimate): November 15, 2007

Study Record Updates

• Last Update Posted (Estimate): August 7, 2014
• Last Update Submitted That Met QC Criteria: July 16, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: 1245.4; EudraCT No 2007-002685-36

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No