Study to Investigate the Relative Bioavailability, Influence of Pantoprazole Coadministration and Food Effect of Different Oral Formulation of BI 113608

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01703858
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arms: 5
• Duration (Months): 4
• Patients Per Site Per Month: 3.7

Study Details

Study Description

Brief Summary

The objective of the trial is to investigate the relative bioavailability, influence of pantoprazole coadministration and food effect of different oral formulations of BI 113608 in healthy male subjects

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: BI 113608 PIB; Drug: BI 113608; Drug: BI 113608; Drug: BI 113608; Drug: pantoprazole 40 mg STADA; Drug: BI 113608	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Randomised, Single Dose, 3-way Cross Over Study to Investigate Relative Bioavailability and Food Effect on Different Formulations of BI 113608 in Healthy Male Subjects, Followed by Fixed Sequence Periods Investigating Influence of Pantoprazole Coadministration and Food Effect on Pharmacokinetics of Different Formulations of BI 113608
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 BI 113608 powder in the bottle for oral solution, oral administration with 240 mL water	Drug: BI 113608 PIB; powder for oral solution
Experimental: 2 BI 113608 conventional tablet formulation	Drug: BI 113608; conventional tablet formulation
Experimental: 3 BI 113608 conventional tablet formulation, fed	Drug: BI 113608; conventional tablet formulation
Experimental: 4 BI 113608 conventional tablet after pantoprazole administration	Drug: pantoprazole 40 mg STADA; film-coated tablet; Drug: BI 113608; conventional tablet formulation
Experimental: 5 BI 113608 conventional tablet formulation, fasted, 0:30 min before fat breakfast	Drug: BI 113608; conventional tablet formulation

Outcome Measures

Primary Outcome Measures

1. Area Under the Concentration-time Curve of the Analyte BI-113608 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) [PK plasma samples were taken at: 2 hours (h) before drug administration and 15 min, 30 min, 45 min, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 14h, 24h, 48h, 72h after drug administration.]

   Area under the concentration-time curve of the analyte BI-113608 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz).

2. Maximum Measured Concentration of the Analyte BI-113608 in Plasma (Cmax) [PK plasma samples were taken at: 2 hours (h) before drug administration and 15 min, 30 min, 45 min, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 14h, 24h, 48h, 72h after drug administration.]

   Maximum measured concentration of the analyte BI-113608 in plasma (Cmax).

Secondary Outcome Measures

1. Area Under the Concentration-time Curve of the Analyte BI-113608 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) [PK plasma samples were taken at: 2 hours (h) before drug administration and 15 min, 30 min, 45 min, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 14h, 24h, 48h, 72h after drug administration.]

   Area under the concentration-time curve of the analyte BI-113608 in plasma over the time interval from 0 extrapolated to infinity (AUC 0-infinity).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion criteria:

1. healthy male subjects

Exclusion criteria:

1. Any relevant deviation from healthy conditions

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1314.3.1 Boehringer Ingelheim Investigational Site	Ingelheim		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

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01703858
• Other Study ID Numbers: 1314.3; 2012-002537-11
• First Posted: Oct 11, 2012
• Last Update Posted: Jan 20, 2017
• Last Verified: Nov 1, 2016

• Additional relevant MeSH terms: Pantoprazole

Study Results

Participant Flow

Pre-assignment Detail	An open label, randomised, single dose, 3-way cross-over study to investigate relative bioavailability and food effect on different formulations of Boehringer-Ingelheim (BI) -113608 in healthy male subjects, followed by fixed sequence periods investigating influence of pantoprazole coadministration and food effect on pharmacokinetics of BI-113608.

Arm/Group Title	A - C - B - D - E	B - A - C - D - E	C - B - A - D - E
Arm/Group Description	Participants first received single dose of oral solution of BI-113608 (50 milligram (mg)) under fasted conditions (A), then they received conventional tablet of BI-113608 (2 tablets of 25 mg) under fed conditions (C) and then the conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions (B) in 3-way crossover periods with washout phase of at least 6 days. After this participants received conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions following administration of pantoprazole 40 mg twice daily for 4 days with an additional 40 mg of pantoprazole 2 hours (h) prior to administration of BI-113608 (D) and then conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions 30 minutes (min) prior to a standardized high-calorie, high-fat breakfast (E). All doses were administered orally.	Participants first received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions (B), then they received oral solution of BI-113608 (50 mg) under fasted conditions (A) and then the conventional tablet of BI-113608 (2 tablets of 25 mg) under fed conditions (C) in 3-way crossover periods with washout phase of at least 6 days. After this participants received conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions following administration of pantoprazole 40 mg twice daily for 4 days with an additional 40 mg of pantoprazole 2 h prior to administration of BI-113608 (D) and then conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions 30 min prior to a standardized high-calorie, high-fat breakfast (E). All doses were administered orally.	Participants first received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fed conditions (C), then they received conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions (B) and then the oral solution of BI-113608 (50 mg) under fasted conditions (A) in 3-way crossover periods with washout phase of at least 6 days. After this participants received conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions following administration of pantoprazole 40 mg twice daily for 4 days with an additional 40 mg of pantoprazole 2 h prior to administration of BI-113608 (D) and then conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions 30 min prior to a standardized high-calorie, high-fat breakfast (E). All doses were administered orally.
Period Title: Overall Study
STARTED	5	5	5
COMPLETED	5	4	5
NOT COMPLETED	0	1	0

Baseline Characteristics

Arm/Group Title	A - C - B - D - E	B - A - C - D - E	C - B - A - D - E	Total
Arm/Group Description	Participants first received single dose of oral solution of BI-113608 (50 milligram (mg)) under fasted conditions (A), then they received conventional tablet of BI-113608 (2 tablets of 25 mg) under fed conditions (C) and then the conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions (B) in 3-way crossover periods with washout phase of at least 6 days. After this participants received conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions following administration of pantoprazole 40 mg twice daily for 4 days with an additional 40 mg of pantoprazole 2 hours (h) prior to administration of BI-113608 (D) and then conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions 30 minutes (min) prior to a standardized high-calorie, high-fat breakfast (E). All doses were administered orally.	Participants first received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions (B), then they received oral solution of BI-113608 (50 mg) under fasted conditions (A) and then the conventional tablet of BI-113608 (2 tablets of 25 mg) under fed conditions (C) in 3-way crossover periods with washout phase of at least 6 days. After this participants received conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions following administration of pantoprazole 40 mg twice daily for 4 days with an additional 40 mg of pantoprazole 2 h prior to administration of BI-113608 (D) and then conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions 30 min prior to a standardized high-calorie, high-fat breakfast (E). All doses were administered orally.	Participants first received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fed conditions (C), then they received conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions (B) and then the oral solution of BI-113608 (50 mg) under fasted conditions (A) in 3-way crossover periods with washout phase of at least 6 days. After this participants received conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions following administration of pantoprazole 40 mg twice daily for 4 days with an additional 40 mg of pantoprazole 2 h prior to administration of BI-113608 (D) and then conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions 30 min prior to a standardized high-calorie, high-fat breakfast (E). All doses were administered orally.	Total of all reporting groups
Overall Participants	5	5	5	15
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	39.4 (8.9)	40.8 (8.6)	41.8 (7.9)	40.7 (7.9)
Gender (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	5 100%	5 100%	5 100%	15 100%

Outcome Measures

1. Primary Outcome

Title	Area Under the Concentration-time Curve of the Analyte BI-113608 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Description	Area under the concentration-time curve of the analyte BI-113608 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz).
Time Frame	PK plasma samples were taken at: 2 hours (h) before drug administration and 15 min, 30 min, 45 min, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 14h, 24h, 48h, 72h after drug administration.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) set: It included all treated subjects who provided at least 1 observation for at least 1 primary PK endpoint without important protocol violations relevant to the evaluation of PK.

Arm/Group Title	A : BI-113608	B : BI-113608	C : BI-113608	D : BI-113608	E : BI-113608
Arm/Group Description	Participants received single dose of oral solution of BI-113608 (50 milligram (mg)) under fasted conditions.	Participants received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions orally.	Participants received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fed conditions orally.	Participants received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions orally following administration of pantoprazole 40 mg twice daily for 4 days with an additional 40 mg of pantoprazole 2 hours (h) prior to administration of BI-113608.	Participants received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions orally 30 minutes (min) prior to a standardized high-calorie, high-fat breakfast.
Measure Participants	15	15	15	15	14
Geometric Mean (Geometric Coefficient of Variation) [nanomol (nmol)* hours (h) / Litre (L)]	936 (27.4)	924 (31.2)	648 (39.3)	900 (32.7)	759 (27.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A : BI-113608, B : BI-113608
	Comments	B : BI-113608 vs. A : BI-113608 - Comparison with oral solution
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMeans) with acceptance range of 80.00 to 125.00%
Statistical Test of Hypothesis	p-Value	0.0000
	Comments
	Method	ANOVA
	Comments	Relative bioavailability was estimated by the ratios of the adjusted geometric means. CIs were calculated based on the residual error.
Method of Estimation	Estimation Parameter	Ratio of Geometric means (%)
	Estimated Value	98.68
	Confidence Interval	(2-Sided) 90%; 92.501 to 105.272
	Parameter Dispersion	Type: Standard Deviation; Value: 10.0
	Estimation Comments	Analysis of variance includes the effects: sequence, subjects nested within sequences, period and treatment in crossover; subject and treatment in fixed sequence. Standard deviation is actually Intra individual geometric coefficient of variation.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B : BI-113608, C : BI-113608
	Comments	C : BI-113608 vs. B : BI-113608 - Food effect
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMeans) with acceptance range of 80.00 to 125.00%
Statistical Test of Hypothesis	p-Value	0.9644
	Comments
	Method	ANOVA
	Comments	Relative bioavailability was estimated by the ratios of the adjusted geometric means. CIs were calculated based on the residual error.
Method of Estimation	Estimation Parameter	Ratio of Geometric means (%)
	Estimated Value	70.16
	Confidence Interval	(2-Sided) 90%; 62.331 to 78.962
	Parameter Dispersion	Type: Standard Deviation; Value: 18.3
	Estimation Comments	Analysis of variance includes the effects: sequence, subjects nested within sequences, period and treatment in crossover; subject and treatment in fixed sequence. Standard deviation is actually Intra individual geometric coefficient of variation.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	B : BI-113608, E : BI-113608
	Comments	E : BI-113608 vs. B : BI-113608 - Food effect
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMeans) with acceptance range of 80.00 to 125.00%
Statistical Test of Hypothesis	p-Value	0.2835
	Comments
	Method	ANOVA
	Comments	Relative bioavailability was estimated by the ratios of the adjusted geometric means. CIs were calculated based on the residual error.
Method of Estimation	Estimation Parameter	Ratio of Geometric means (%)
	Estimated Value	83.36
	Confidence Interval	(2-Sided) 90%; 73.648 to 94.346
	Parameter Dispersion	Type: Standard Deviation; Value: 18.8
	Estimation Comments	Analysis of variance includes the effects: sequence, subjects nested within sequences, period and treatment in crossover; subject and treatment in fixed sequence. Standard deviation is actually Intra individual geometric coefficient of variation.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	C : BI-113608, E : BI-113608
	Comments	E : BI-113608 vs. C : BI-113608 - Food effect
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMeans) with acceptance range of 80.00 to 125.00%
Statistical Test of Hypothesis	p-Value	0.1599
	Comments
	Method	ANOVA
	Comments	Relative bioavailability was estimated by the ratios of the adjusted geometric means. CIs were calculated based on the residual error.
Method of Estimation	Estimation Parameter	Ratio of Geometric means (%)
	Estimated Value	117.18
	Confidence Interval	(2-Sided) 90%; 104.923 to 130.867
	Parameter Dispersion	Type: Standard Deviation; Value: 16.7
	Estimation Comments	Analysis of variance includes the effects: sequence, subjects nested within sequences, period and treatment in crossover; subject and treatment in fixed sequence. Standard deviation is actually Intra individual geometric coefficient of variation.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	B : BI-113608, D : BI-113608
	Comments	D : BI-113608 vs. B : BI-113608 - Pantoprazole effect
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMeans) with acceptance range of 80.00 to 125.00%
Statistical Test of Hypothesis	p-Value	0.0020
	Comments
	Method	ANOVA
	Comments	Relative bioavailability was estimated by the ratios of the adjusted geometric means. CIs were calculated based on the residual error.
Method of Estimation	Estimation Parameter	Ratio of Geometric means (%)
	Estimated Value	97.40
	Confidence Interval	(2-Sided) 90%; 88.072 to 107.719
	Parameter Dispersion	Type: Standard Deviation; Value: 15.8
	Estimation Comments	Analysis of variance includes the effects: sequence, subjects nested within sequences, period and treatment in crossover; subject and treatment in fixed sequence. Standard deviation is actually Intra individual geometric coefficient of variation.

2. Primary Outcome

Title	Maximum Measured Concentration of the Analyte BI-113608 in Plasma (Cmax)
Description	Maximum measured concentration of the analyte BI-113608 in plasma (Cmax).
Time Frame	PK plasma samples were taken at: 2 hours (h) before drug administration and 15 min, 30 min, 45 min, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 14h, 24h, 48h, 72h after drug administration.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) set: It included all treated subjects who provided at least 1 observation for at least 1 primary PK endpoint without important protocol violations relevant to the evaluation of PK.

Arm/Group Title	A : BI-113608	B : BI-113608	C : BI-113608	D : BI-113608	E : BI-113608
Arm/Group Description	Participants received single dose of oral solution of BI-113608 (50 milligram (mg)) under fasted conditions.	Participants received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions orally.	Participants received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fed conditions orally.	Participants received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions orally following administration of pantoprazole 40 mg twice daily for 4 days with an additional 40 mg of pantoprazole 2 hours (h) prior to administration of BI-113608.	Participants received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions orally 30 minutes (min) prior to a standardized high-calorie, high-fat breakfast.
Measure Participants	15	15	15	15	14
Geometric Mean (Geometric Coefficient of Variation) [nmol/L]	271 (44.6)	242 (47.5)	132 (77.8)	196 (50.0)	227 (53.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A : BI-113608, B : BI-113608
	Comments	B : BI-113608 vs. A : BI-113608 - Comparison with oral solution
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMeans) with acceptance range of 80.00 to 125.00%
Statistical Test of Hypothesis	p-Value	0.1261
	Comments
	Method	ANOVA
	Comments	Relative bioavailability was estimated by the ratios of the adjusted geometric means. CIs were calculated based on the residual error.
Method of Estimation	Estimation Parameter	Ratio of Geometric means (%)
	Estimated Value	89.26
	Confidence Interval	(2-Sided) 90%; 75.893 to 104.973
	Parameter Dispersion	Type: Standard Deviation; Value: 25.3
	Estimation Comments	Analysis of variance includes the effects: sequence, subjects nested within sequences, period and treatment in crossover; subject and treatment in fixed sequence. Standard deviation is actually Intra individual geometric coefficient of variation.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B : BI-113608, C : BI-113608
	Comments	C : BI-113608 vs. B : BI-113608 - Food effect
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMeans) with acceptance range of 80.00 to 125.00%
Statistical Test of Hypothesis	p-Value	0.9808
	Comments
	Method	ANOVA
	Comments	Relative bioavailability was estimated by the ratios of the adjusted geometric means. CIs were calculated based on the residual error.
Method of Estimation	Estimation Parameter	Ratio of Geometric means (%)
	Estimated Value	54.57
	Confidence Interval	(2-Sided) 90%; 40.711 to 73.157
	Parameter Dispersion	Type: Standard Deviation; Value: 47.4
	Estimation Comments	Analysis of variance includes the effects: sequence, subjects nested within sequences, period and treatment in crossover; subject and treatment in fixed sequence. Standard deviation is actually Intra individual geometric coefficient of variation.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	B : BI-113608, E : BI-113608
	Comments	E : BI-113608 vs. B : BI-113608 - Food effect
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMeans) with acceptance range of 80.00 to 125.00%
Statistical Test of Hypothesis	p-Value	0.1449
	Comments
	Method	ANOVA
	Comments	Relative bioavailability was estimated by the ratios of the adjusted geometric means. CIs were calculated based on the residual error.
Method of Estimation	Estimation Parameter	Ratio of Geometric means (%)
	Estimated Value	94.88
	Confidence Interval	(2-Sided) 90%; 72.175 to 124.731
	Parameter Dispersion	Type: Standard Deviation; Value: 43.2
	Estimation Comments	Analysis of variance includes the effects: sequence, subjects nested within sequences, period and treatment in crossover; subject and treatment in fixed sequence. Standard deviation is actually Intra individual geometric coefficient of variation.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	C : BI-113608, E : BI-113608
	Comments	E : BI-113608 vs. C : BI-113608 - Food effect
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMeans) with acceptance range of 80.00 to 125.00%
Statistical Test of Hypothesis	p-Value	0.9463
	Comments
	Method	ANOVA
	Comments	Relative bioavailability was estimated by the ratios of the adjusted geometric means. CIs were calculated based on the residual error.
Method of Estimation	Estimation Parameter	Ratio of Geometric means (%)
	Estimated Value	169.46
	Confidence Interval	(2-Sided) 90%; 124.093 to 231.419
	Parameter Dispersion	Type: Standard Deviation; Value: 49.7
	Estimation Comments	Analysis of variance includes the effects: sequence, subjects nested within sequences, period and treatment in crossover; subject and treatment in fixed sequence. Standard deviation is actually Intra individual geometric coefficient of variation.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	B : BI-113608, D : BI-113608
	Comments	D : BI-113608 vs. B : BI-113608 - Pantoprazole effect
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMeans) with acceptance range of 80.00 to 125.00%
Statistical Test of Hypothesis	p-Value	0.4564
	Comments
	Method	ANOVA
	Comments	Relative bioavailability was estimated by the ratios of the adjusted geometric means. CIs were calculated based on the residual error.
Method of Estimation	Estimation Parameter	Ratio of Geometric means (%)
	Estimated Value	81.06
	Confidence Interval	(2-Sided) 90%; 65.811 to 99.848
	Parameter Dispersion	Type: Standard Deviation; Value: 33.3
	Estimation Comments	Analysis of variance includes the effects: sequence, subjects nested within sequences, period and treatment in crossover; subject and treatment in fixed sequence. Standard deviation is actually Intra individual geometric coefficient of variation.

3. Secondary Outcome

Title	Area Under the Concentration-time Curve of the Analyte BI-113608 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity)
Description	Area under the concentration-time curve of the analyte BI-113608 in plasma over the time interval from 0 extrapolated to infinity (AUC 0-infinity).
Time Frame	PK plasma samples were taken at: 2 hours (h) before drug administration and 15 min, 30 min, 45 min, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 14h, 24h, 48h, 72h after drug administration.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) set: It included all treated subjects who provided at least 1 observation for at least 1 primary PK endpoint without important protocol violations relevant to the evaluation of PK.

Arm/Group Title	A : BI-113608	B : BI-113608	C : BI-113608	D : BI-113608	E : BI-113608
Arm/Group Description	Participants received single dose of oral solution of BI-113608 (50 milligram (mg)) under fasted conditions.	Participants received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions orally.	Participants received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fed conditions orally.	Participants received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions orally following administration of pantoprazole 40 mg twice daily for 4 days with an additional 40 mg of pantoprazole 2 hours (h) prior to administration of BI-113608.	Participants received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions orally 30 minutes (min) prior to a standardized high-calorie, high-fat breakfast.
Measure Participants	15	15	15	15	14
Geometric Mean (Geometric Coefficient of Variation) [nmol*h/L]	938 (27.4)	926 (31.2)	650 (39.3)	902 (32.7)	761 (27.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A : BI-113608, B : BI-113608
	Comments	B : BI-113608 vs. A : BI-113608 - Comparison with oral solution
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMeans) with acceptance range of 80.00 to 125.00%
Statistical Test of Hypothesis	p-Value	0.0000
	Comments
	Method	ANOVA
	Comments	Relative bioavailability was estimated by the ratios of the adjusted geometric means. CIs were calculated based on the residual error.
Method of Estimation	Estimation Parameter	Ratio of Geometric means (%)
	Estimated Value	98.66
	Confidence Interval	(2-Sided) 90%; 92.500 to 105.225
	Parameter Dispersion	Type: Standard Deviation; Value: 9.9
	Estimation Comments	Analysis of variance includes the effects: sequence, subjects nested within sequences, period and treatment in crossover; subject and treatment in fixed sequence. Standard deviation is actually Intra individual geometric coefficient of variation.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B : BI-113608, C : BI-113608
	Comments	C : BI-113608 vs. B : BI-113608 - Food effect
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMeans) with acceptance range of 80.00 to 125.00%
Statistical Test of Hypothesis	p-Value	0.9635
	Comments
	Method	ANOVA
	Comments	Relative bioavailability was estimated by the ratios of the adjusted geometric means. CIs were calculated based on the residual error.
Method of Estimation	Estimation Parameter	Ratio of Geometric means (%)
	Estimated Value	70.24
	Confidence Interval	(2-Sided) 90%; 62.430 to 79.038
	Parameter Dispersion	Type: Standard Deviation; Value: 18.3
	Estimation Comments	Analysis of variance includes the effects: sequence, subjects nested within sequences, period and treatment in crossover; subject and treatment in fixed sequence. Standard deviation is actually Intra individual geometric coefficient of variation.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	B : BI-113608, E : BI-113608
	Comments	E : BI-113608 vs. B : BI-113608 - Food effect
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMeans) with acceptance range of 80.00 to 125.00%
Statistical Test of Hypothesis	p-Value	0.2771
	Comments
	Method	ANOVA
	Comments	Relative bioavailability was estimated by the ratios of the adjusted geometric means. CIs were calculated based on the residual error.
Method of Estimation	Estimation Parameter	Ratio of Geometric means (%)
	Estimated Value	83.46
	Confidence Interval	(2-Sided) 90%; 73.774 to 94.412
	Parameter Dispersion	Type: Standard Deviation; Value: 18.7
	Estimation Comments	Analysis of variance includes the effects: sequence, subjects nested within sequences, period and treatment in crossover; subject and treatment in fixed sequence. Standard deviation is actually Intra individual geometric coefficient of variation.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	C : BI-113608, E : BI-113608
	Comments	E : BI-113608 vs. C : BI-113608 - Food effect
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMeans) with acceptance range of 80.00 to 125.00%
Statistical Test of Hypothesis	p-Value	0.1584
	Comments
	Method	ANOVA
	Comments	Relative bioavailability was estimated by the ratios of the adjusted geometric means. CIs were calculated based on the residual error.
Method of Estimation	Estimation Parameter	Ratio of Geometric means (%)
	Estimated Value	117.16
	Confidence Interval	(2-Sided) 90%; 104.958 to 130.787
	Parameter Dispersion	Type: Standard Deviation; Value: 16.6
	Estimation Comments	Analysis of variance includes the effects: sequence, subjects nested within sequences, period and treatment in crossover; subject and treatment in fixed sequence. Standard deviation is actually Intra individual geometric coefficient of variation.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	B : BI-113608, D : BI-113608
	Comments	D : BI-113608 vs. B : BI-113608 - Pantoprazole effect
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMeans) with acceptance range of 80.00 to 125.00%
Statistical Test of Hypothesis	p-Value	0.0020
	Comments
	Method	ANOVA
	Comments	Relative bioavailability was estimated by the ratios of the adjusted geometric means. CIs were calculated based on the residual error.
Method of Estimation	Estimation Parameter	Ratio of Geometric means (%)
	Estimated Value	97.41
	Confidence Interval	(2-Sided) 90%; 88.066 to 107.741
	Parameter Dispersion	Type: Standard Deviation; Value: 15.8
	Estimation Comments	Analysis of variance includes the effects: sequence, subjects nested within sequences, period and treatment in crossover; subject and treatment in fixed sequence. Standard deviation is actually Intra individual geometric coefficient of variation.

Adverse Events

Time Frame	From first drug administration until 14 days after the last drug administration, up to 42 days.
Arm/Group Title	A : BI-113608		B : BI-113608		C : BI-113608		Pantoprazole 40mg		D : BI-113608		E : BI-113608
Arm/Group Description	Participants received single dose of oral solution of BI-113608 (50 milligram (mg)) under fasted conditions.		Participants received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions orally.		Participants received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fed conditions orally.		Participants received single dose of Pantoprazole 40mg alone twice daily for 4 days with an additional 40 mg of pantoprazole 2 hours (h) prior to administration of BI-113608.		Participants received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions orally following administration of pantoprazole 40 mg twice daily for 4 days with an additional 40 mg of pantoprazole 2 hours (h) prior to administration of BI-113608.		Participants received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions orally 30 minutes (min) prior to a standardized high-calorie, high-fat breakfast.
All Cause Mortality
	A : BI-113608		B : BI-113608		C : BI-113608		Pantoprazole 40mg		D : BI-113608		E : BI-113608
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	A : BI-113608		B : BI-113608		C : BI-113608		Pantoprazole 40mg		D : BI-113608		E : BI-113608
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	A : BI-113608		B : BI-113608		C : BI-113608		Pantoprazole 40mg		D : BI-113608		E : BI-113608
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/15 (40%)		6/15 (40%)		7/15 (46.7%)		3/15 (20%)		4/15 (26.7%)		5/14 (35.7%)
Eye disorders
Lacrimation increased	0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/14 (0%)
Gastrointestinal disorders
Abdominal distension	1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/14 (0%)
Abdominal pain upper	0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/14 (0%)
Diarrhoea	0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/14 (0%)
Frequent bowel movements	0/15 (0%)		1/15 (6.7%)		1/15 (6.7%)		0/15 (0%)		1/15 (6.7%)		0/14 (0%)
Toothache	0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/14 (0%)
General disorders
Feeling cold	0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/14 (0%)
Oedema peripheral	0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/14 (0%)
Infections and infestations
Nasopharyngitis	0/15 (0%)		0/15 (0%)		0/15 (0%)		1/15 (6.7%)		1/15 (6.7%)		1/14 (7.1%)
Rhinitis	0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/14 (0%)
Musculoskeletal and connective tissue disorders
Bone pain	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		1/14 (7.1%)
Neck pain	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		1/14 (7.1%)
Pain in extremity	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/14 (0%)
Nervous system disorders
Headache	5/15 (33.3%)		5/15 (33.3%)		5/15 (33.3%)		2/15 (13.3%)		2/15 (13.3%)		1/14 (7.1%)
Respiratory, thoracic and mediastinal disorders
Cough	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		1/14 (7.1%)
Skin and subcutaneous tissue disorders
Pruritus	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		1/14 (7.1%)
Vascular disorders
Haematoma	1/15 (6.7%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/14 (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.