Bioequivalence of a Fixed Dose Combination Tablet of Empagliflozin/Metformin Extended Release Compared With Mono Compound Tablets in Healthy Male and Female

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02266472
• Collaborator: Eli Lilly and Company (Industry)
• Enrollment: 30
• Location: 1
• Arms: 2
• Duration (Days): 30
• Patients Per Site Per Month: 30.4

Study Details

Study Description

Brief Summary

The purpose of this trial is to investigate bioequivalence of a newly developed fixed dose combination (FDC) tablet containing empagliflozin and metformin extended release compared to the free combination of empagliflozin and metformin extended release under fed conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: metformin; Drug: empagliflozin/metformin; Drug: empagliflozin	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Bioequivalence of a Fixed Dose Combination Tablet of Empagliflozin/Metformin Extended Release (10 mg/1000 mg) Compared With the Free Combination of Empagliflozin and Metformin Extended Release Tablets in Healthy Subjects Following a High-fat, High-caloric Meal (an Open-label, Randomised, Single Dose, Crossover Trial)
• Study Start Date: Nov 1, 2014
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fixed dose combination Single dose empagliflozin/metformin	Drug: empagliflozin/metformin; Single dose empagliflozin/metformin given as fixed-dose combination tablet
Active Comparator: Single tablets combination single doses empagliflozin and metformin	Drug: metformin; single dose of metformin given as tablets; Drug: empagliflozin; single dose of empagliflozin given as tablet

Outcome Measures

Primary Outcome Measures

1. AUC0-tz of Empagliflozin in Plasma [-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration]

   Area under the concentration-time curve of empagliflozin in plasma over the time interval from 0 to the time of the last quantifiable concentration (AUC0-tz)

2. AUC0-tz of Metformin in Plasma [-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration]

   Area under the concentration-time curve of metformin in plasma over the time interval from 0 to the time of the last quantifiable concentration (AUC0-tz)

3. Cmax of Empagliflozin in Plasma [-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration]

   Maximum measured concentration of the empagliflozin in plasma

4. Cmax of Metformin in Plasma [-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration]

   Maximum measured concentration of the metformin in plasma

Secondary Outcome Measures

1. AUC0-infinity of Empagliflozin in Plasma [-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration]

   Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.

2. AUC0-infinity of Metformin in Plasma [-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration]

   Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.

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

• age of 18 to 55 years

• body mass index (BMI) of 18.5 to 29.9 kg/m2

• additional inclusion criteria may apply

Exclusion criteria:

• Any finding in the medical examination (including BP, PR or ECG) deviating from normal and judged as clinically relevant by the investigator

• Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg or diastolic blood pressure outside the range of 50 to 90 mmHg or pulse rate outside the range of 45 to 90 bpm

• Any laboratory value outside the reference range that the investigator considers to be of clinical relevance

• Any evidence of a concomitant disease judged as clinically relevant by the investigator

• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders

• Surgery of the gastrointestinal tract that could interfere with kinetics of the trial medication

• Diseases of the central nervous system (including but not limited to any kind of seizures and stroke), and other relevant neurological disorders or psychiatric disorders

• additional exclusion criteria may apply

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Boehringer Ingelheim
• Eli Lilly and Company

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT02266472
• Other Study ID Numbers: 1276.28; 2014-002360-32
• First Posted: Oct 17, 2014
• Last Update Posted: Mar 9, 2017
• Last Verified: Jan 1, 2017

• Additional relevant MeSH terms: Metformin; Empagliflozin

Study Results

Participant Flow

Pre-assignment Detail	This was an open-label, randomised, 2-way crossover trial with 2 treatments (T and R) and 2 treatment sequences (T_R and R_T). Trial drug administrations of the 2 single dose treatments were separated by a washout period of at least 7 days.

Arm/Group Title	Fed 10mg+1000mg Fixed Dose Combination (FDC)/Single (TR)	Fed 10mg+1000mg Single/FDC (RT)
Arm/Group Description	Subjects received in period 1 a single dose of 10 mg empagliflozin/1000 mg metformin hydrochloride (HCl) extended release (XR) (1 tablet) with 240 mL of water after intake of a high-fat, high-caloric meal, followed in period 2 with a single dose of 10 mg empagliflozin (1 tablet) together with 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal. 2 treatments separated by a wash-out period of at least 7 days.	Subjects received in period 1 a single dose of 10 mg empagliflozin (1 tablet) together with 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal, followed in period 2 with a single dose of 10 mg empagliflozin/1000 mg metformin HCl XR (1 tablet) with 240 mL of water after intake of a high-fat, high-caloric meal. 2 treatments separated by a wash-out period of at least 7 days.
Period Title: Period 1+ Washout
STARTED	15	15
COMPLETED	15	15
NOT COMPLETED	0	0
Period Title: Period 1+ Washout
STARTED	15	15
COMPLETED	15	15
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Fed 10mg+1000mg FDC/Single (TR)	Fed 10mg+1000mg Single/FDC (RT)	Total
Arm/Group Description	Subjects received in period 1 a single dose of 10 mg empagliflozin/1000 mg metformin hydrochloride (HCl) extended release (XR) (1 tablet) with 240 mL of water after intake of a high-fat, high-caloric meal, followed in period 2 with a single dose of 10 mg empagliflozin (1 tablet) together with 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal. 2 treatments separated by a wash-out period of at least 7 days.	Subjects received in period 1 a single dose of 10 mg empagliflozin (1 tablet) together with 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal, followed in period 2 with a single dose of 10 mg empagliflozin/1000 mg metformin HCl XR (1 tablet) with 240 mL of water after intake of a high-fat, high-caloric meal. 2 treatments separated by a wash-out period of at least 7 days.	Total of all reporting groups
Overall Participants	15	15	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.5 (8.1)	33.7 (10.1)	33.6 (9.0)
Sex: Female, Male (Count of Participants)
Female	6 40%	8 53.3%	14 46.7%
Male	9 60%	7 46.7%	16 53.3%

Outcome Measures

1. Primary Outcome

Title	AUC0-tz of Empagliflozin in Plasma
Description	Area under the concentration-time curve of empagliflozin in plasma over the time interval from 0 to the time of the last quantifiable concentration (AUC0-tz)
Time Frame	-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration

Outcome Measure Data

Analysis Population Description

Pharmacokinetic set (PKS) included all treated subjects that provided at least 1 observation for at least 1 primary endpoint without important protocol violations with respect to the statistical evaluation of the pharmacokinetic endpoints.

Arm/Group Title	Fed 10mg+ 1000mg FDC (T)	Fed 10mg+1000mg Single (R)
Arm/Group Description	Subjects received a single dose of 10 mg empagliflozin/1000 mg metformin HCl XR (1 tablet) with 240 mL of water after intake of a high-fat, high-caloric meal.	Subjects received a single dose of 10 mg empagliflozin (1 tablet) together with a single dose of 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal.
Measure Participants	30	30
Geometric Mean (Geometric Coefficient of Variation) [nmol*h/L]	2190 (18.1)	2210 (16.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fed 10mg+ 1000mg FDC (T), Fed 10mg+1000mg Single (R)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The assessment of bioequivalence was based on 2-sided 90% CIs for the ratios (test to reference treatment) of the adjusted gMeans of the primary endpoints, with acceptance range of 80.00 to 125.00 %.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments	ANOVA model on the logarithmic scale including random effects for 'subjects within sequences' & fixed effect for 'sequence', 'period' & 'treatment'.
Method of Estimation	Estimation Parameter	ratio of the adjusted means
	Estimated Value	99.11
	Confidence Interval	(2-Sided) 90%; 96.40 to 101.89
	Parameter Dispersion	Type: Standard Deviation; Value: 6.3
	Estimation Comments	Relative bioavailability of empagliflozin was estimated by the adjusted gMean ratio of Fed 10mg+1000mg FDC divided by Fed 10mg+1000mg Single. Standard deviation is actually intraindividual geometric coefficient variation (gCV).

2. Primary Outcome

Title	AUC0-tz of Metformin in Plasma
Description	Area under the concentration-time curve of metformin in plasma over the time interval from 0 to the time of the last quantifiable concentration (AUC0-tz)
Time Frame	-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration

Outcome Measure Data

Analysis Population Description

PKS

Arm/Group Title	Fed 10mg+ 1000mg FDC (T)	Fed 10mg+1000mg Single (R)
Arm/Group Description	Subjects received a single dose of 10 mg empagliflozin/1000 mg metformin HCl XR (1 tablet) with 240 mL of water after intake of a high-fat, high-caloric meal.	Subjects received a single dose of 10 mg empagliflozin (1 tablet) together with a single dose of 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal.
Measure Participants	29	30
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	10800 (20.1)	10700 (22.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fed 10mg+ 1000mg FDC (T), Fed 10mg+1000mg Single (R)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The assessment of bioequivalence was based on 2-sided 90% confidence intervals (CIs) for the ratios (test to reference treatment) of the adjusted geometric means (gMeans) of the primary endpoints,using an acceptance range of 80.00 to 125.00 %.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments	ANOVA model on the logarithmic scale including random effects for 'subjects within sequences' & fixed effect for 'sequence', 'period' & 'treatment'.
Method of Estimation	Estimation Parameter	ratio of the adjusted means
	Estimated Value	101.25
	Confidence Interval	(2-Sided) 90%; 96.54 to 106.19
	Parameter Dispersion	Type: Standard Deviation; Value: 10.7
	Estimation Comments	Relative bioavailability of metformin was estimated by the adjusted gMean ratio of Fed 10mg+1000mg FDC divided by Fed 10mg+1000mg Single. Standard deviation is actually intraindividual geometric coefficient variation (gCV).

3. Primary Outcome

Title	Cmax of Empagliflozin in Plasma
Description	Maximum measured concentration of the empagliflozin in plasma
Time Frame	-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration

Outcome Measure Data

Analysis Population Description

PKS

Arm/Group Title	Fed 10mg+ 1000mg FDC (T)	Fed 10mg+1000mg Single (R)
Arm/Group Description	Subjects received a single dose of 10 mg empagliflozin/1000 mg metformin HCl XR (1 tablet) with 240 mL of water after intake of a high-fat, high-caloric meal.	Subjects received a single dose of 10 mg empagliflozin (1 tablet) together with a single dose of 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal.
Measure Participants	30	30
Geometric Mean (Geometric Coefficient of Variation) [nmol/L]	243 (23.1)	245 (20.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fed 10mg+ 1000mg FDC (T), Fed 10mg+1000mg Single (R)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The assessment of bioequivalence was based on 2-sided 90% CIs for the ratios (test to reference treatment) of the adjusted gMeans of the primary endpoints, with acceptance range of 80.00 to 125.00%.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments	ANOVA model on the logarithmic scale including random effects for 'subjects within sequences' & fixed effect for 'sequence', 'period' & 'treatment'.
Method of Estimation	Estimation Parameter	ratio of the adjusted means
	Estimated Value	99.12
	Confidence Interval	(2-Sided) 90%; 93.69 to 104.87
	Parameter Dispersion	Type: Standard Deviation; Value: 12.9
	Estimation Comments	Relative bioavailability of empagliflozin was estimated by the adjusted gMean ratio of Fed10mg+1000mg FDC divided by Fed10mg+1000mg Single. Standard deviation is actually intraindividual geometric coefficient variation (gCV).

4. Primary Outcome

Title	Cmax of Metformin in Plasma
Description	Maximum measured concentration of the metformin in plasma
Time Frame	-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration

Outcome Measure Data

Analysis Population Description

PKS

Arm/Group Title	Fed 10mg+ 1000mg FDC (T)	Fed 10mg+1000mg Single (R)
Arm/Group Description	Subjects received a single dose of 10 mg empagliflozin/1000 mg metformin HCl XR (1 tablet) with 240 mL of water after intake of a high-fat, high-caloric meal.	Subjects received a single dose of 10 mg empagliflozin (1 tablet) together with a single dose of 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal.
Measure Participants	29	30
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	1170 (25.5)	1080 (25.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fed 10mg+ 1000mg FDC (T), Fed 10mg+1000mg Single (R)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The assessment of bioequivalence was based on 2-sided 90% CIs for the ratios (test to reference treatment) of the adjusted gMeans of the primary endpoints, with acceptance range of 80.00 to 125.00%.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments	ANOVA model on the logarithmic scale including random effects for 'subjects within sequences' & fixed effect for 'sequence', 'period' & 'treatment'.
Method of Estimation	Estimation Parameter	ratio of the adjusted means
	Estimated Value	108.58
	Confidence Interval	(2-Sided) 90%; 104.17 to 113.17
	Parameter Dispersion	Type: Standard Deviation; Value: 9.3
	Estimation Comments	Relative bioavailability of metformin was estimated by the adjusted gMean ratio of Fed10mg+1000mg FDC divided by Fed10mg+1000mg Single. Standard deviation is actually intraindividual geometric coefficient variation (gCV).

5. Secondary Outcome

Title	AUC0-infinity of Empagliflozin in Plasma
Description	Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.
Time Frame	-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration

Outcome Measure Data

Analysis Population Description

PKS

Arm/Group Title	Fed 10mg+ 1000mg FDC (T)	Fed 10mg+1000mg Single (R)
Arm/Group Description	Subjects received a single dose of 10 mg empagliflozin/1000 mg metformin HCl XR (1 tablet) with 240 mL of water after intake of a high-fat, high-caloric meal.	Subjects received a single dose of 10 mg empagliflozin (1 tablet) together with a single dose of 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal.
Measure Participants	30	30
Geometric Mean (Geometric Coefficient of Variation) [nmol*h/L]	2230 (18.0)	2260 (16.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fed 10mg+ 1000mg FDC (T), Fed 10mg+1000mg Single (R)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The assessment of bioequivalence was based on 2-sided 90% CIs for the ratios (test to reference treatment) of the adjusted gMeans of the primary endpoints, with acceptance range of 80.00 to 125.00%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratio of the adjusted means
	Estimated Value	98.89
	Confidence Interval	(2-Sided) 90%; 96.18 to 101.67
	Parameter Dispersion	Type: Standard Deviation; Value: 6.3
	Estimation Comments	Relative bioavailability of empagliflozin was estimated by the adjusted gMean ratio of Fed10mg+1000mg FDC divided by Fed10mg+1000mg Single. Standard deviation is actually intraindividual geometric coefficient variation (gCV).

6. Secondary Outcome

Title	AUC0-infinity of Metformin in Plasma
Description	Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.
Time Frame	-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration

Outcome Measure Data

Analysis Population Description

PKS

Arm/Group Title	Fed 10mg+ 1000mg FDC (T)	Fed 10mg+1000mg Single (R)
Arm/Group Description	Subjects received a single dose of 10 mg empagliflozin/1000 mg metformin HCl XR (1 tablet) with 240 mL of water after intake of a high-fat, high-caloric meal.	Subjects received a single dose of 10 mg empagliflozin (1 tablet) together with a single dose of 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal.
Measure Participants	29	30
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	11000 (20.8)	10800 (22.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fed 10mg+ 1000mg FDC (T), Fed 10mg+1000mg Single (R)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The assessment of bioequivalence was based on 2-sided 90% CIs for the ratios (test to reference treatment) of the adjusted gMeans of the primary endpoints, with acceptance range of 80.00 to 125.00%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratio of the adjusted means
	Estimated Value	101.37
	Confidence Interval	(2-Sided) 90%; 96.53 to 106.45
	Parameter Dispersion	Type: Standard Deviation; Value: 11.0
	Estimation Comments	Relative bioavailability of metformin was estimated by the adjusted gMean ratio of Fed10mg+1000mg FDC divided by Fed10mg+1000mg Single. Standard deviation is actually intraindividual geometric coefficient variation (gCV).

Adverse Events

Time Frame	From first drug administration until the end-of-trial examination (Up to 14 days)
Arm/Group Title	Fed 10mg+1000mg Single (R)		Fed 10mg+ 1000mg FDC (T)
Arm/Group Description	Subjects received a single dose of 10 mg empagliflozin (1 tablet) together with a single dose of 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal.		Subjects received a single dose of 10 mg empagliflozin/1000 mg metformin HCl XR (1 tablet) with 240 mL of water after intake of a high-fat, high-caloric meal.
All Cause Mortality
	Fed 10mg+1000mg Single (R)		Fed 10mg+ 1000mg FDC (T)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Fed 10mg+1000mg Single (R)		Fed 10mg+ 1000mg FDC (T)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Fed 10mg+1000mg Single (R)		Fed 10mg+ 1000mg FDC (T)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/30 (30%)		5/30 (16.7%)
Gastrointestinal disorders
Diarrhoea	2/30 (6.7%)		1/30 (3.3%)
Nausea	2/30 (6.7%)		0/30 (0%)
Nervous system disorders
Headache	5/30 (16.7%)		4/30 (13.3%)

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.