Trial Outcomes & Findings for A Study in Healthy Men to Test How Itraconazole Influences the Amount of BI 894416 in the Blood (NCT NCT03722173)

Last Updated: 2023-08-14

Results Overview

AUC0-tz, area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 to the last quantifiable data point is presented. Standard Error (SE) is actually a geometric (g) SE. Pharmacokinetic (PK) samples were collected 3 hours (h) prior dosing and 15 minutes (min), 30 min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 34h after BI 894416 on day 1 of both periods and additionally on 48h and 72h after BI 894416 administration in period 2.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

14 participants

Primary outcome timeframe

Up to 34 h (period 1) and up to 72 h (period 2) (please refer timeframe in detail in description)

Results posted on

2023-08-14

Participant Flow

Open-label, two-treatment periods one-way crossover trial in healthy male participants to compare BI 894416+Itraconazole (Treatment(T)) versus BI 894416 alone (Reference(R)). All participants underwent treatment R in Period 1 (Visit 2) and treatment T in Period 2 (Visit 3). There was at least 6 days washout between the administrations of BI 894416.

All participants were screened for eligibility to participate in the trial. Participants attended specialist site which would then ensure that all participants met all inclusion/exclusion criteria. Participants were not to be entered to trial treatment if any one of the specific entry criteria were not met.

Participant milestones

Participant milestones
Measure	BI 894416 Alone (R) / BI 894416+Itraconazole (T) Participants were administered 3 milligram (mg) BI 894416 tablet (1 mg X 3 tablets) orally on Day 1 alone in treatment period 1 (R), and along with 20 milliliter (mL) of 10 mg/ mL Itraconazole oral solution in treatment period 2 (T). In period 2 (T), participants received 200 mg ((20 milliliter (mL)) of Itraconazole oral solution once daily for 5 days, from Day -3 to Day 2. On Day 1 participants received additionally after the Itraconazole dosing, 3 mg BI 894416 tablet (1 mg X 3 tablets) orally in treatment period 2 (T). Both treatment periods were separated by a washout period of at least 6 days between BI 894416 administrations. In both treatments, BI 894416 was administered to subjects in the fasting state.
Period 1 (2 Days) STARTED	14
Period 1 (2 Days) COMPLETED	14
Period 1 (2 Days) NOT COMPLETED	0
Washout Period STARTED	14
Washout Period COMPLETED	14
Washout Period NOT COMPLETED	0
Period 2 (4 Days) STARTED	14
Period 2 (4 Days) COMPLETED	14
Period 2 (4 Days) NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study in Healthy Men to Test How Itraconazole Influences the Amount of BI 894416 in the Blood

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BI 894416 Alone (R) / BI 894416+Itraconazole (T) n=14 Participants Participants were administered 3 milligram (mg) BI 894416 tablet (1 mg X 3 tablets) orally on Day 1 alone in treatment period 1 (R), and along with 20 milliliter (mL) of 10 mg/ mL Itraconazole oral solution in treatment period 2 (T). In period 2 (T), participants received 200 mg ((20 milliliter (mL)) of Itraconazole oral solution once daily for 5 days, from Day -3 to Day 2. On Day 1 participants received additionally after the Itraconazole dosing, 3 mg BI 894416 tablet (1 mg X 3 tablets) orally in treatment period 2 (T). Both treatment periods were separated by a washout period of at least 6 days between BI 894416 administrations. In both treatments, BI 894416 was administered to subjects in the fasting state.
Age, Continuous	40.9 Years STANDARD_DEVIATION 8.8 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 34 h (period 1) and up to 72 h (period 2) (please refer timeframe in detail in description)

Population: Pharmacokinetic (PK) parameter set (PKS): PKS included all subjects in the TS who provided at least 1 PK parameter that was not excluded because of important protocol deviation (IPDs) relevant to the statistical evaluation the PK endpoints.

Outcome measures

Outcome measures
Measure	BI 894416 Alone (R) n=14 Participants Participants were administered 3 milligram (mg) BI 894416 tablet (1 mg X 3 tablets) orally on Day 1 alone in treatment period 1 (R).	BI 894416 + Itraconazole (T) n=14 Participants Participants received 200 mg ((20 milliliter (mL)) of Itraconazole oral solution once daily for 5 days, from Day -3 to Day 2. On Day 1 participants received additionally after the Itraconazole dosing, 3 mg BI 894416 tablet (1 mg X 3 tablets) orally.
Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)	371.77 Nanomolehour / Litre (nmolh/ L) Standard Error 1.13	526.50 Nanomolehour / Litre (nmolh/ L) Standard Error 1.13

PRIMARY outcome

Timeframe: Up to 34 h (period 1) and up to 72 h (period 2) (please refer timeframe in detail in description)

Cmax, maximum measured concentration of BI 894416 in plasma is presented. Standard error (SE) is actually geometric (g) SE. Pharmacokinetic (PK) samples were collected 3 hours (h) prior dosing and 15minutes (min), 30 min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 34h after BI 894416 on day 1 of both periods and additionally on 48h and 72h after BI 894416 administration in period 2.

Outcome measures

Outcome measures
Measure	BI 894416 Alone (R) n=14 Participants Participants were administered 3 milligram (mg) BI 894416 tablet (1 mg X 3 tablets) orally on Day 1 alone in treatment period 1 (R).	BI 894416 + Itraconazole (T) n=14 Participants Participants received 200 mg ((20 milliliter (mL)) of Itraconazole oral solution once daily for 5 days, from Day -3 to Day 2. On Day 1 participants received additionally after the Itraconazole dosing, 3 mg BI 894416 tablet (1 mg X 3 tablets) orally.
Maximum Measured Concentration of BI 894416 in Plasma (Cmax)	59.93 Nanomole/ Litre (nmol/ L) Standard Error 1.07	67.91 Nanomole/ Litre (nmol/ L) Standard Error 1.07

SECONDARY outcome

Timeframe: Up to 34 h (period 1) and up to 72 h (period 2) (please refer timeframe in detail in description)

AUC0-∞, area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 extrapolated to infinity is presented. Standard error (SE) is actually geometric (g) SE. Pharmacokinetic (PK) samples were collected 3 hours (h) prior dosing and 15minutes (min), 30 min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 34h after BI 894416 on day 1 of both periods and additionally on 48h and 72h after BI 894416 administration in period 2.

Outcome measures

Outcome measures
Measure	BI 894416 Alone (R) n=14 Participants Participants were administered 3 milligram (mg) BI 894416 tablet (1 mg X 3 tablets) orally on Day 1 alone in treatment period 1 (R).	BI 894416 + Itraconazole (T) n=14 Participants Participants received 200 mg ((20 milliliter (mL)) of Itraconazole oral solution once daily for 5 days, from Day -3 to Day 2. On Day 1 participants received additionally after the Itraconazole dosing, 3 mg BI 894416 tablet (1 mg X 3 tablets) orally.
Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	384.01 Nanomolehour / Litre (nmolh/ L) Standard Error 1.13	547.36 Nanomolehour / Litre (nmolh/ L) Standard Error 1.13

Adverse Events

BI 894416 Alone (R)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Itraconazole Alone

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

BI 894416 + Itraconazole (T)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	BI 894416 Alone (R) n=14 participants at risk Participants were administered 3 milligram (mg) BI 894416 tablet (1 mg X 3 tablets) orally on Day 1 alone in treatment period 1 (R).	Itraconazole Alone n=14 participants at risk Participants were administered 10 mg/ mL Itraconazole oral solution in treatment period 2 only (T). Itraconazole was administered once daily from Day -3 to Day 1 before administration of BI 894416 on Day 1.	BI 894416 + Itraconazole (T) n=14 participants at risk Participants received 200 mg ((20 milliliter (mL)) of Itraconazole oral solution once daily for 5 days, from Day -3 to Day 2. On Day 1 participants received additionally after the Itraconazole dosing, 3 mg BI 894416 tablet (1 mg X 3 tablets) orally.
Gastrointestinal disorders Diarrhoea	0.00% 0/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.	50.0% 7/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.	7.1% 1/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.	7.1% 1/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.	0.00% 0/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.
Gastrointestinal disorders Flatulence	0.00% 0/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.	7.1% 1/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.	0.00% 0/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.
Nervous system disorders Headache	21.4% 3/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.	0.00% 0/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.	7.1% 1/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.
Nervous system disorders Dysgeusia	0.00% 0/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.	7.1% 1/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.	0.00% 0/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.
General disorders Chest pain	0.00% 0/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.	0.00% 0/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.	7.1% 1/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	0.00% 0/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.	7.1% 1/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.	0.00% 0/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.
Injury, poisoning and procedural complications Contusion	0.00% 0/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.	0.00% 0/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.	7.1% 1/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.
Vascular disorders Haematoma	0.00% 0/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.	0.00% 0/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.	7.1% 1/14 • From first drug administration until the individual subject's end of trial date (at least 6 days for period 1 and between 7 and 14 days for period 2). Treated set (TS): This subject set included all subjects who received at least one dose of study drug.

Additional Information

Boehringer Ingelheim, Call Centre

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place