Trial Outcomes & Findings for Interaction of BI 691751 With Itraconazole (NCT NCT02044393)

Results Overview

AUC0-tz: area under the concentration-time curve of BI 691751 in plasma and whole blood over the time interval from 0 up to the last quantifiable concentration.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

20 participants

Primary outcome timeframe

from day 1 to 31 days postdose relative to BI 691751 administration (h:min): -2:00, 0:10, 0:20, 0:40, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 47:00, 71:00, 95:00, 119:00, 143:00, 215:00, 287:00, 383:00, 551:00, 719:00h.

Results posted on

2015-12-16

Participant Flow

Participant milestones

Participant milestones
Measure	Itraconazole (IT) +BI 691751 / BI 691751 Subjects in treatment sequence of tested drug treatment in period 1, then reference drug treatment in period 2 (T/R): two capsules of 100 mg itraconazole were given twice daily on Day -3 (loading dose) and once daily on Day -2 to Day 7 (10 days of itraconazol treatment in total). In addition, 1 tablet of 10 mg BI 691751 was given as a single dose on Day 1 (corresponding to the fourth day of the 10-day itraconazole treatment) in period 1. One tablet of 10 mg BI 691751 was given as a single dose on Day 1 in period 2. The BI 691751 single dose administrations in the 2 treatment periods were separated by a washout period of at least 7 weeks. Oral administration with 240 mL water after intake of a standardised meal.	BI 691751 / IT+BI 691751 Subjects in treatment sequence of reference drug treatment in period 1, then tested drug treatment in period 2 (R/T): One tablet of 10 mg BI 691751 was given as a single dose on Day 1 in period 1. Two capsules of 100 mg itraconazole were given twice daily on Day -3 (loading dose) and once daily on Day -2 to Day 7 (10 days of itraconazol treatment in total), and, 1 tablet of 10 mg BI 691751 was given as a single dose on Day 1 (corresponding to the fourth day of the 10-day itraconazole treatment) in period 2. Oral administration with 240 mL water after intake of a standaridsed meal.
Period 1 STARTED	10	10
Period 1 COMPLETED	10	10
Period 1 NOT COMPLETED	0	0
Period 2 STARTED	10	10
Period 2 COMPLETED	10	10
Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Interaction of BI 691751 With Itraconazole

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Itraconazole (IT) +BI 691751 / BI 691751 n=10 Participants Subjects in treatment sequence of tested drug treatment in period 1, then reference drug treatment in period 2 (T/R): two capsules of 100 mg itraconazole were given twice daily on Day -3 (loading dose) and once daily on Day -2 to Day 7 (10 days of itraconazol treatment in total). In addition, 1 tablet of 10 mg BI 691751 was given as a single dose on Day 1 (corresponding to the fourth day of the 10-day itraconazole treatment) in period 1. One tablet of 10 mg BI 691751 was given as a single dose on Day 1 in period 2. The BI 691751 single dose administrations in the 2 treatment periods were separated by a washout period of at least 7 weeks. Oral administration with 240 mL water after intake of a standardised meal.	BI 691751 / IT+BI 691751 n=10 Participants Subjects in treatment sequence of reference drug treatment in period 1, then tested drug treatment in period 2 (R/T): One tablet of 10 mg BI 691751 was given as a single dose on Day 1 in period 1. Two capsules of 100 mg itraconazole were given twice daily on Day -3 (loading dose) and once daily on Day -2 to Day 7 (10 days of itraconazol treatment in total), and, 1 tablet of 10 mg BI 691751 was given as a single dose on Day 1 (corresponding to the fourth day of the 10-day itraconazole treatment) in period 2. Oral administration with 240 mL water after intake of a standaridsed meal.	Total n=20 Participants Total of all reporting groups
Age, Continuous	35.1 years STANDARD_DEVIATION 9.9 • n=5 Participants	37.4 years STANDARD_DEVIATION 6.6 • n=7 Participants	36.3 years STANDARD_DEVIATION 8.3 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants

PRIMARY outcome

Timeframe: from day 1 to 31 days postdose relative to BI 691751 administration (h:min): -2:00, 0:10, 0:20, 0:40, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 47:00, 71:00, 95:00, 119:00, 143:00, 215:00, 287:00, 383:00, 551:00, 719:00h.

Population: Pharmacokinetic Set (PKS): included all subjects from the TS who provided at least one primary or secondary pharmacokinetic endpoint in any period that is judged as evaluable for pharmacokinetics and is not affected by protocol violations relevant to the statistical evaluation of bioavailability

AUC0-tz: area under the concentration-time curve of BI 691751 in plasma and whole blood over the time interval from 0 up to the last quantifiable concentration.

Outcome measures

Outcome measures
Measure	BI 691751 n=20 Participants single dose BI 691751 BI 691751: 10 mg single dose oral administration with 240 mL water after intake of a standard meal.	IT + BI 691751 n=20 Participants Two capsules of 100 mg IT were given twice daily on Day -3 and once daily on Day -2 to Day 7. 1 tablet of 10 mg BI 691751 was given as a single dose on Day 1 with 240 mL water after intake of a standard meal.
AUC0-tz (Area Under the Concentration-time Curve of BI 691751 in Plasma and Whole Blood Over the Time Interval From 0 up to the Last Quantifiable Concentration) in plasma	2830 nmol*h/L Geometric Coefficient of Variation 34.6	2090 nmol*h/L Geometric Coefficient of Variation 43.2
AUC0-tz (Area Under the Concentration-time Curve of BI 691751 in Plasma and Whole Blood Over the Time Interval From 0 up to the Last Quantifiable Concentration) in whole blood	25000 nmol*h/L Geometric Coefficient of Variation 25.8	21600 nmol*h/L Geometric Coefficient of Variation 25.8

PRIMARY outcome

Timeframe: From day 1 to 31 days postdose relative to BI 691751 administration (h:min): -2:00, 0:10, 0:20, 0:40, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 47:00, 71:00, 95:00, 119:00, 143:00, 215:00, 287:00, 383:00, 551:00, 719:00h.

Population: PKS

Cmax (maximum measured concentration of BI 691751 in plasma and whole blood).

Outcome measures

Outcome measures
Measure	BI 691751 n=20 Participants single dose BI 691751 BI 691751: 10 mg single dose oral administration with 240 mL water after intake of a standard meal.	IT + BI 691751 n=20 Participants Two capsules of 100 mg IT were given twice daily on Day -3 and once daily on Day -2 to Day 7. 1 tablet of 10 mg BI 691751 was given as a single dose on Day 1 with 240 mL water after intake of a standard meal.
Cmax (Maximum Measured Concentration of BI 691751 in Plasma and Whole Blood) in plasma	157 nmol/L Geometric Coefficient of Variation 24.4	150 nmol/L Geometric Coefficient of Variation 34.1
Cmax (Maximum Measured Concentration of BI 691751 in Plasma and Whole Blood) in whole blood	217 nmol/L Geometric Coefficient of Variation 16.0	203 nmol/L Geometric Coefficient of Variation 21.4

SECONDARY outcome

Timeframe: from day 1 to 31 days postdose relative to BI 691751 administration time: -2:00, 0:10, 0:20, 0:40, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 47:00, 71:00, 95:00, 119:00, 143:00, 215:00, 287:00, 383:00, 551:00, 719:00h.

Population: PKS

AUC0-infinity (area under the concentration-time curve of BI 691751 in plasma and whole blood over the time interval from 0 extrapolated to infinity).