Relative Bioavailability of Single Dose Empagliflozin (BI 10773) When Co-administered With Multiple Doses of 600 mg Gemfibrozil Compared to Single Dose Treatment With Empagliflozin (BI 10773) When Given Alone in Healthy Volunteers

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01301742
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arms: 2

Study Details

Study Description

Brief Summary

To investigate the relative bioavailability of BI 10773 following coadministration with 600 mg gemfibrozil bid dosed to steady-state in comparison to BI 10773 when given alone.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: BI 10773; Drug: Gemfibrozil; Drug: BI 10773	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Relative Bioavailability of Single Dose BI 10773 Co-administered With Multiple Doses of 600 mg Gemfibrozil Bid Compared to Single Dose Treatment of BI 10773 Alone in Healthy Volunteers - a Phase I, Open-label, Randomised, 2-way Crossover Trial
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: BI 10773 Subject to receive one single dose BI 10773	Drug: BI 10773; 1 tablet single dose BI 10773 in the morning; Drug: Gemfibrozil; Gemfibrozil 600 mg bid for 5 days
Experimental: BI 10773 plus gemfibrozil Subject to receive one single dose BI 10773 plus 600 mg gemfibrozil bid for 5 days	Drug: BI 10773; 1 tablet single dose BI 10773 in the morning

Outcome Measures

Primary Outcome Measures

1. Total Empa: Area Under the Curve 0 to Infinity (AUC0-∞) [0 minutes (min), 20 min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 23h, 36h, 47h, 71h after the first dose]

   Area under the plasma concentration-time curve of the analyte from time 0 extrapolated to infinity. The standard deviation presented in the analysis is actually the intra-individual geometric standard deviation (gCV).

2. Total Empa: Maximum Measured Concentration (Cmax) [0 minutes (min), 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 23h, 36h, 47h, 71h after the first dose]

   Maximum measured concentration of total Empagliflozin (Empa) in plasma, per period. The standard deviation presented in the analysis is actually the intra-individual geometric standard deviation (gCV).

Secondary Outcome Measures

1. Total Empa: Area Under the Curve 0 to Time of Last Quantifiable Data Point (AUC0-tz) [0 minutes (min), 20 min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 23h, 36h, 47h, 71h after the first dose]

   Area under the plasma concentration-time curve of the analyte from time 0 to the time of the last quantifiable data point. The standard deviation presented in the analyses is actually the intra-individual geometric standard deviation (gCV).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion criteria:

• Healthy male and female subjects

Exclusion criteria:

• Any finding of the medical examination (including Blood Pressure, Pulse Rate and Electrocardiogram) deviating from normal and of clinical relevance

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1245.58.1 Boehringer Ingelheim Investigational Site	Biberach		Germany

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: NCT01301742
• Other Study ID Numbers: 1245.58; 2010-023152-85
• First Posted: Feb 23, 2011
• Last Update Posted: Jun 18, 2014
• Last Verified: May 1, 2014

• Additional relevant MeSH terms: Empagliflozin; Gemfibrozil

Study Results

Participant Flow

Arm/Group Title	Empa First, Then Empa and Gemfibrozil	Empa and Gemfibrozil First, Then Empa
Arm/Group Description	Empagliflozin 25mg (Empa) was given as a single dose on Day 1, followed by a washout period of at least 7 days, followed by Gemfibrozil 600mg given twice daily for 5 days starting on day -2 and empa given as a single dose on Day 1, with gemfibrozil under steady-state conditions.	Gemfibrozil 600mg was given twice daily for 5 days starting on day -2 and empagliflozin 25mg (empa) was given as a single dose on Day 1, with gemfibrozil under steady-state conditions. This was followed by a washout period of at least 7 days, followed by Empa given as a single dose on Day 1.
Period Title: First Intervention
STARTED	9	9
COMPLETED	9	9
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	9	9
COMPLETED	9	9
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	9	9
COMPLETED	9	9
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description	The two treatments given in a randomised order were: Empagliflozin 25mg (Empa) was given as a single dose on Day 1 Gemfibrozil 600mg was given twice daily for 5 days starting on day -2 and empa was given as a single dose on Day 1, with gemfibrozil under steady-state conditions. Between treatments there was a washout period of at least 7 days.
Overall Participants	18
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.1 (10.2)
Sex: Female, Male (Count of Participants)
Female	7 38.9%
Male	11 61.1%

Outcome Measures

1. Primary Outcome

Title	Total Empa: Area Under the Curve 0 to Infinity (AUC0-∞)
Description	Area under the plasma concentration-time curve of the analyte from time 0 extrapolated to infinity. The standard deviation presented in the analysis is actually the intra-individual geometric standard deviation (gCV).
Time Frame	0 minutes (min), 20 min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 23h, 36h, 47h, 71h after the first dose

Outcome Measure Data

Analysis Population Description

PK set: All subjects who had taken at least 1 dose of trial medication who provided at least 1 observation for at least 1 primary pharmacokinetic (PK) endpoint without an important protocol violation with respect to the PK evaluation.

Arm/Group Title	Empa Alone	Empa and Gemfibrozil
Arm/Group Description	Empagliflozin (Empa) 25mg given as a single dose on Day 1.	Gemfibrozil 600mg was given twice daily for 5 days starting on day -2 and empagliflozin 25mg (empa) was given as a single dose on Day 1, with gemfibrozil under steady-state conditions.
Measure Participants	18	18
Geometric Mean (Geometric Coefficient of Variation) [nmol*h/L]	4708.33 (7.5)	7462.74 (7.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Empa Alone, Empa and Gemfibrozil
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Ratio calculated as empa and gemfibrozil divided by empa alone
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	158.50
	Confidence Interval	(2-Sided) 90%; 151.77 to 165.53
	Parameter Dispersion	Type: Standard Deviation; Value: 7.5
	Estimation Comments	Standard deviation is actually the intra-individual geometric coefficient of variation (gCV)

2. Primary Outcome

Title	Total Empa: Maximum Measured Concentration (Cmax)
Description	Maximum measured concentration of total Empagliflozin (Empa) in plasma, per period. The standard deviation presented in the analysis is actually the intra-individual geometric standard deviation (gCV).
Time Frame	0 minutes (min), 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 23h, 36h, 47h, 71h after the first dose

Outcome Measure Data

Analysis Population Description

PK set: All subjects who had taken at least 1 dose of trial medication who provided at least 1 observation for at least 1 primary pharmacokinetic (PK) endpoint without an important protocol violation with respect to the PK evaluation.

Arm/Group Title	Empa Alone	Empa and Gemfibrozil
Arm/Group Description	Empagliflozin (Empa) 25mg given as a single dose on Day 1.	Gemfibrozil 600mg was given twice daily for 5 days starting on day -2 and empagliflozin 25mg (empa) was given as a single dose on Day 1, with gemfibrozil under steady-state conditions.
Measure Participants	18	18
Geometric Mean (Geometric Coefficient of Variation) [nmol/L]	602.24 (13.8)	692.59 (13.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Empa Alone, Empa and Gemfibrozil
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Ratio calculated as empa and gemfibrozil divided by empa alone
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	115.00
	Confidence Interval	(2-Sided) 90%; 106.15 to 124.59
	Parameter Dispersion	Type: Standard Deviation; Value: 13.8
	Estimation Comments	Standard deviation is actually the intra-individual gCV

3. Secondary Outcome

Title	Total Empa: Area Under the Curve 0 to Time of Last Quantifiable Data Point (AUC0-tz)
Description	Area under the plasma concentration-time curve of the analyte from time 0 to the time of the last quantifiable data point. The standard deviation presented in the analyses is actually the intra-individual geometric standard deviation (gCV).
Time Frame	0 minutes (min), 20 min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 23h, 36h, 47h, 71h after the first dose

Outcome Measure Data

Analysis Population Description

PK set: All subjects who had taken at least 1 dose of trial medication who provided at least 1 observation for at least 1 primary pharmacokinetic (PK) endpoint without an important protocol violation with respect to the PK evaluation.

Arm/Group Title	Empa Alone	Empa and Gemfibrozil
Arm/Group Description	Empagliflozin (Empa) 25mg given as a single dose on Day 1.	Gemfibrozil 600mg was given twice daily for 5 days starting on day -2 and empagliflozin 25mg (empa) was given as a single dose on Day 1, with gemfibrozil under steady-state conditions.
Measure Participants	18	18
Geometric Mean (Geometric Coefficient of Variation) [nmol*h/L]	4643.81 (7.7)	7350.84 (7.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Empa Alone, Empa and Gemfibrozil
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Ratio calculated as empa and gemfibrozil divided by empa alone
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	158.29
	Confidence Interval	(2-Sided) 90%; 151.41 to 165.49
	Parameter Dispersion	Type: Standard Deviation; Value: 7.7
	Estimation Comments	Standard deviation is actually the intra-individual gCV

Adverse Events

Time Frame	First administration of trial medication until next administration of trial medication or up to post-study visit, 20 days
Arm/Group Title	Empa Alone		Empa and Gemfibrozil		Gemfibrozil Alone
Arm/Group Description	Empagliflozin (Empa) 25mg given as a single dose on Day 1.		Gemfibrozil 600mg was given twice daily for 5 days starting on day -2 and empagliflozin 25mg (empa) was given as a single dose on Day 1, with gemfibrozil under steady-state conditions.		Between the first gemfibrozil administration and the empagliflozin administration, for the Empa and gemfibrozil treatment period.
All Cause Mortality
	Empa Alone		Empa and Gemfibrozil		Gemfibrozil Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Empa Alone		Empa and Gemfibrozil		Gemfibrozil Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/18 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Empa Alone		Empa and Gemfibrozil		Gemfibrozil Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/18 (44.4%)		3/18 (16.7%)		6/18 (33.3%)
Gastrointestinal disorders
Diarrhoea	0/18 (0%)		0/18 (0%)		1/18 (5.6%)
Dyspepsia	0/18 (0%)		0/18 (0%)		1/18 (5.6%)
Infections and infestations
Oral herpes	1/18 (5.6%)		0/18 (0%)		0/18 (0%)
Rhinitis	0/18 (0%)		0/18 (0%)		1/18 (5.6%)
Musculoskeletal and connective tissue disorders
Muscle disorder	1/18 (5.6%)		0/18 (0%)		0/18 (0%)
Muscle tightness	1/18 (5.6%)		0/18 (0%)		0/18 (0%)
Pain in extremity	0/18 (0%)		1/18 (5.6%)		0/18 (0%)
Nervous system disorders
Dizziness	1/18 (5.6%)		1/18 (5.6%)		0/18 (0%)
Headache	4/18 (22.2%)		1/18 (5.6%)		1/18 (5.6%)
Renal and urinary disorders
Nocturia	0/18 (0%)		0/18 (0%)		1/18 (5.6%)
Pollakiuria	0/18 (0%)		0/18 (0%)		1/18 (5.6%)
Respiratory, thoracic and mediastinal disorders
Dysphonia	0/18 (0%)		0/18 (0%)		1/18 (5.6%)
Skin and subcutaneous tissue disorders
Erythema	0/18 (0%)		1/18 (5.6%)		0/18 (0%)
Vascular disorders
Haematoma	2/18 (11.1%)		0/18 (0%)		0/18 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.