Effect of Food and Increased Gastric pH Value on Bioavail... | NCT01983566

ID	Type	Description	Link
2013-003967-74	EudraCT Number	EudraCT

Effect of Food and Increased Gastric pH Value on Bioavail... | NCT01983566 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
BI 207127 fasted	Active Comparator	patient to receive BI 207127 as a single dose in fasted state	Drug: BI 207127
BI 207127 high fat	Experimental	patient to receive BI 207127 as a single dose after a high fat breakfast	Drug: BI 207127 high fat
BI 207127 low fat	Experimental	patient to receive BI 207127 as a single dose after a low fat breakfast	Drug: BI 207127 low fat
BI 207127 with Omeprazole	Experimental	patient to receive BI 207127 as a single dose after 4 days treatment with Omeprazole 40 mg once a day	Drug: BI 207127 with Omeprazole

Name	Type	Description	Arm Group Labels	Other Names
BI 207127 high fat	Drug	BI 207127 as a single dose after a high fat breakfast	BI 207127 high fat

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
AUC(0-tz)	Area under the concentration-time curve of deleobuvir in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz)	1 hour (h) before drug administration and 30 minutes (min), 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h and 48h after drug administration
Cmax	Maximum measured concentration of deleobuvir in plasma (Cmax)	1 hour (h) before drug administration and 30 minutes (min), 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h and 48h after drug administration

Secondary Outcomes

Measure	Description	Time Frame
AUC(0-inf)	Area under the concentration-time curve of deleobuvir in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)	1 hour (h) before drug administration and 30 minutes (min), 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h and 48h after drug administration

Contacts/Locations Module

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Dele Fasted / Dele High Fat / Dele + OMP / Dele Low Fat	Each subject received a single dose of 3 x 200 mg Deleobuvir (Dele) film-coated tablets after an overnight fast of at least 10 hours (h), followed by a washout phase of at least 6 days; then each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised high-fat, high-calorie meal after an overnight fast of at least 10 h, followed by a washout phase of at least 6 days; then each subject received a single dose of 3 x 200 mg Dele film-coated tablets after an overnight fast of at least 10 h after 4 days of pre-treatment with a 40 mg Omeprazole (OMP) gastro-resistant hard capsule once daily, followed by a washout phase of at least 6 days; then each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised low-fat meal after an overnight fast of at least 10 h. All medications were administered oral with 240 mL of water.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Wash-Out 1

Type	Comment	Milestone Data
STARTED		FG0004 subjects FG0014 subjects FG0024 subjects FG0034 subjects
COMPLETED		FG0004 subjects FG0014 subjects FG0024 subjects FG0034 subjects
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects

Test Period 2

Type	Comment	Milestone Data
STARTED		FG0004 subjects FG0014 subjects FG0024 subjects FG0034 subjects
COMPLETED		FG0004 subjects FG0014 subjects FG0024 subjects FG0034 subjects
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects

Wash-Out 2

Type	Comment	Milestone Data
STARTED		FG0002 subjectsSubjects starting may not equal number completing the previous period due to early study termination FG0013 subjectsSubjects starting may not equal number completing the previous period due to early study termination FG0022 subjectsSubjects starting may not equal number completing the previous period due to early study termination FG0034 subjects
COMPLETED		FG0002 subjects FG0013 subjects FG0022 subjects FG0034 subjects
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects

Test Period 3

Type	Comment	Milestone Data
STARTED		FG0002 subjects FG0013 subjects FG0022 subjects FG0034 subjects
COMPLETED		FG0002 subjects FG0013 subjects FG0022 subjects FG0034 subjects
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects

Wash-Out 3

Type	Comment	Milestone Data
STARTED		FG0000 subjectsSubjects starting may not equal number completing the previous period due to early study termination FG0010 subjectsSubjects starting may not equal number completing the previous period due to early study termination FG0020 subjectsSubjects starting may not equal number completing the previous period due to early study termination FG0030 subjectsSubjects starting may not equal number completing the previous period due to early study termination
COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects

Test Period 4

Type	Comment	Milestone Data
STARTED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects
COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects

Arm/Group Information

ID	Title	Description
BG000	Dele Fasted / Dele High Fat / Dele + OMP / Dele Low Fat	Dele fasted, followed by a washout phase, followed by Dele after a standardised high-fat, high- calorie meal, followed by a washout phase, followed by Dele after a 4 days pre-treatment with a 40 mg Omeprazole (OMP) gastro-resistant hard capsule once daily, followed by a washout phase, followed by Dele after a standardised low-fat meal. Each Dele intake is a single dose of 3x 200mg Dele film-coated tablets after an overnight fast of at least 10 h. The duration of a washout phase was at least 6 days.
BG001	Dele High Fat / Dele Low Fat / Dele Fasted / Dele + OMP	Dele after a standardised high-fat, high-calorie meal, followed by a washout phase, followed by Dele after a standardised low-fat meal, followed by a washout phase, followed by Dele fasted, followed by a washout phase, followed by Dele after a 4 days pre-treatment with a 40 mg OMP gastro-resistant hard capsule once daily. Each Dele intake is a single dose of 3x 200mg Dele film-coated tablets after an overnight fast of at least 10 h. The duration of a washout phase was at least 6 days.
BG002	Dele Low Fat / Dele + OMP / Dele High Fat / Dele Fasted	Dele after a standardised low-fat meal, followed by a washout phase, followed by Dele after a 4 days pre-treatment with a 40 mg OMP gastro-resistant hard capsule once daily, followed by a washout phase, followed by Dele after a standardised high-fat, high-calorie meal, followed by a washout phase, followed by Dele fasted. Each Dele intake is a single dose of 3x 200mg Dele film-coated tablets after an overnight fast of at least 10 h. The duration of a washout phase was at least 6 days.
BG003	Dele + OMP / Dele Fasted / Dele Low Fat / Dele High Fat	Dele after a 4 days pre-treatment with a 40 mg OMP gastro-resistant hard capsule once daily, followed by a washout phase, followed by Dele fasted, followed by a washout phase, followed by Dele after a standardised low-fat meal, followed by a washout phase, followed by Dele after a standardised high-fat, high-calorie meal. Each Dele intake is a single dose of 3x 200mg Dele film-coated tablets after an overnight fast of at least 10 h. The duration of a washout phase was at least 6 days.
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG0004 BG0014 BG0024 BG0034 BG00416

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG0009790± 60.2 OG00116900± 98.8 OG00214200± 46.8 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002	The difference between the expected means for log(Dele low fat) and log(Dele fasted) was estimated by the differences in the adjusted means (Least Squares Means), and a 2 sided 90% confidence interval (CI) based on the t-distribution was computed. These were then back transformed. The estimation model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequence', 'period', and 'treatment'.	ANOVA		0.3944	The p-value relates to the null hypothesis of non-equivalence (bioequivalence test). P-value for ratio outside interval 80-125%.	Geometric mean ratio (%)	115.80			2-Sided	90	63.52	211.11			This model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequence', 'period', and 'treatment'. The statistical analysis result is based on the adjusted means.

Primary

Cmax

Maximum measured concentration of deleobuvir in plasma (Cmax)

PKS

Posted

Geometric Mean

Geometric Coefficient of Variation

nmol/L

1 hour (h) before drug administration and 30 minutes (min), 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h and 48h after drug administration

ID	Title	Description
OG000	Dele Fasted	Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after an overnight fast of at least 10 h. The tablets were administered oral with 240 mL of water.
OG001	Dele High Fat	Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised high-fat, high-calorie meal after an overnight fast of at least 10 h. The tablets were administered oral with 240 mL of water.
OG002	Dele Low Fat	Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised low-fat meal after an overnight fast of at least 10 h. The tablets were administered oral with 240 mL of water.
OG003	Dele + OMP

Secondary

AUC(0-inf)

Area under the concentration-time curve of deleobuvir in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)

PKS - Due to premature discontinuation of the study, this endpoint was not evaluated.

Posted

1 hour (h) before drug administration and 30 minutes (min), 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h and 48h after drug administration

ID	Title	Description
OG000	Dele Fasted	Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after an overnight fast of at least 10 h. The tablets were administered oral with 240 mL of water.
OG001	Dele High Fat	Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised high-fat, high-calorie meal after an overnight fast of at least 10 h. The tablets were administered oral with 240 mL of water.
OG002	Dele Low Fat	Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised low-fat meal after an overnight fast of at least 10 h. The tablets were administered oral with 240 mL of water.
OG003

Arm/Groups

ID	Title	Description	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Dele Fasted	Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after an overnight fast of at least 10 h. The tablets were administered oral with 240 mL of water.	11	2	11
EG001	Dele High Fat	Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised high-fat, high-calorie meal after an overnight fast of at least 10 h. The tablets were administered oral with 240 mL of water.	10	1	10
EG002	Dele Low Fat	Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised low-fat meal after an overnight fast of at least 10 h. The tablets were administered oral with 240 mL of water.	12	4	12
EG003	Dele + OMP	Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after an overnight fast of at least 10 h after 4 days of pre-treatment with a 40 mg Omeprazole (OMP) gastro-resistant hard capsule once daily. All medications were administered oral with 240 mL of water.	10	7	10
EG004	OMP Alone	One gastro-resistant hard capsule of Omeprazole (OMP) (40 mg) once daily in the evening for 4 days administered oral with 240 mL of water.	10	0	10

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0002 affected11 at risk EG0010 affected10 at risk EG0022 affected12 at risk EG0035 affected10 at risk EG0040 affected10 at risk
Diarrhoea	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected11 at risk EG0010 affected10 at risk EG0020 affected12 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected10 at risk EG0020 affected12 at risk EG003
Fatigue	General disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected11 at risk EG0010 affected10 at risk EG0022 affected12 at risk EG003
Headache	Nervous system disorders	MEDDRA 17.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected10 at risk EG0021 affected12 at risk EG003
Syncope	Nervous system disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected11 at risk EG0011 affected10 at risk EG0020 affected12 at risk EG003
Dizziness	Nervous system disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected11 at risk EG0010 affected10 at risk EG0021 affected12 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MEDDRA 17.0	Systematic Assessment	EG0000 affected11 at risk EG0010 affected10 at risk EG0020 affected12 at risk EG003

Ancestor Terms

ID	Term
D053799	2-Pyridinylmethylsulfinylbenzimidazoles
D013454	Sulfoxides
D013457	Sulfur Compounds
D009930	Organic Chemicals
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D001562	Benzimidazoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002	The difference between the expected means for log(Dele low fat) and log(Dele fasted) was estimated by the differences in the adjusted means (Least Squares Means), and a 2 sided 90% CI based on the t-distribution was computed. These were then back transformed. This estimation model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequence', 'period', and 'treatment'.	ANOVA		0.3674	The p-value relates to the null hypothesis of non-equivalence (bioequivalence test). P-value for ratio outside interval 80-125%.	Geometric mean ratio (%)	114.83			2-Sided	90	74.803	176.281			This model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequence', 'period', and 'treatment'. The statistical analysis result is based on the adjusted means.	Yes	Non-Inferiority or Equivalence	The actual number of subjects analyzed is 16. No formal statistical hypothesis was tested.