Trial Outcomes & Findings for A Study in Healthy Men to Test Whether Four Capsules of 25 mg Nintedanib Are Taken up in the Body in the Same Way as One 100 mg Capsule (NCT NCT04938453)

Last Updated: 2023-07-17

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

20 participants

Primary outcome timeframe

For both arms: Within 3 hours (h) before and 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h, 34 h, 48 h and 72h after nintedanib administration.

Results posted on

2023-07-17

Participant Flow

This was a phase I trial to test the relative bioavailability of 100 milligram (mg) nintedanib (Ofev®) given as four capsules of 25 mg compared to one capsule of 100 mg following oral administration in healthy male subjects (an open-label, randomised, single-dose, two-period, two-sequence crossover study).

All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Participant milestones

Participant milestones
Measure	Nintedanib 4 X 25 mg (T) / Nintedanib 1 X 100 mg (R) On Day 1 of Period 1 participants were administered one single intake of 4 soft gelatin capsules of 25 milligram (mg) of nintedanib (total administered dose = 100 mg) (test treatment (T)) orally with 240 milliliter (mL) of water after breakfast. On Day 1 of Period 2 participants were administered once 1 soft gelatin capsule of 100 mg of nintedanib (reference treatment (R)) orally with 240 mL of water after breakfast. There was a washout period of at least 7 days between the treatments.	Nintedanib 1 X 100 mg (R) / Nintedanib 4 X 25 mg (T) On Day 1 of Period 1 participants were administered once 1 soft gelatin capsule of 100 milligram (mg) of nintedanib (reference treatment (R)) orally with 240 milliliter (mL) of water after breakfast. On Day 1 of Period 2 participants were administered one single intake of 4 soft gelatin capsules of 25 mg of nintedanib (total administered dose = 100 mg) (test treatment (T)) orally with 240 mL of water after breakfast. There was a washout period of at least 7 days between the treatments.
Period 1 STARTED	10	10
Period 1 COMPLETED	10	10
Period 1 NOT COMPLETED	0	0
Washout Period 1 STARTED	10	10
Washout Period 1 COMPLETED	9	9
Washout Period 1 NOT COMPLETED	1	1
Period 2 STARTED	9	9
Period 2 COMPLETED	9	9
Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Nintedanib 4 X 25 mg (T) / Nintedanib 1 X 100 mg (R) On Day 1 of Period 1 participants were administered one single intake of 4 soft gelatin capsules of 25 milligram (mg) of nintedanib (total administered dose = 100 mg) (test treatment (T)) orally with 240 milliliter (mL) of water after breakfast. On Day 1 of Period 2 participants were administered once 1 soft gelatin capsule of 100 mg of nintedanib (reference treatment (R)) orally with 240 mL of water after breakfast. There was a washout period of at least 7 days between the treatments.	Nintedanib 1 X 100 mg (R) / Nintedanib 4 X 25 mg (T) On Day 1 of Period 1 participants were administered once 1 soft gelatin capsule of 100 milligram (mg) of nintedanib (reference treatment (R)) orally with 240 milliliter (mL) of water after breakfast. On Day 1 of Period 2 participants were administered one single intake of 4 soft gelatin capsules of 25 mg of nintedanib (total administered dose = 100 mg) (test treatment (T)) orally with 240 mL of water after breakfast. There was a washout period of at least 7 days between the treatments.
Washout Period 1 Adverse Event	0	1
Washout Period 1 Physician Decision	1	0

Baseline Characteristics

A Study in Healthy Men to Test Whether Four Capsules of 25 mg Nintedanib Are Taken up in the Body in the Same Way as One 100 mg Capsule

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nintedanib 1 X 100 mg (R) / Nintedanib 4 X 25 mg (T) n=10 Participants On Day 1 of Period 1 participants were administered once 1 soft gelatin capsule of 100 milligram (mg) of nintedanib (reference treatment (R)) orally with 240 milliliter (mL) of water after breakfast. On Day 1 of Period 2 participants were administered one single intake of 4 soft gelatin capsules of 25 mg of nintedanib (total administered dose = 100 mg) (test treatment (T)) orally with 240 mL of water after breakfast. There was a washout period of at least 7 days between the treatments.	Nintedanib 4 X 25 mg (T) / Nintedanib 1 X 100 mg (R) n=10 Participants On Day 1 of Period 1 participants were administered one single intake of 4 soft gelatin capsules of 25 milligram (mg) of nintedanib (total administered dose = 100 mg) (test treatment (T)) orally with 240 milliliter (mL) of water after breakfast. On Day 1 of Period 2 participants were administered once 1 soft gelatin capsule of 100 mg of nintedanib (reference treatment (R)) orally with 240 mL of water after breakfast. There was a washout period of at least 7 days between the treatments.	Total n=20 Participants Total of all reporting groups
Age, Continuous	35.2 Years STANDARD_DEVIATION 10.1 • n=5 Participants	32.4 Years STANDARD_DEVIATION 7.8 • n=7 Participants	33.8 Years STANDARD_DEVIATION 8.9 • 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
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: For both arms: Within 3 hours (h) before and 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h, 34 h, 48 h and 72h after nintedanib administration.

Population: Pharmacokinetic (PK) parameter analysis set (PKS): The PKS included all subjects in the TS who provided at least 1 PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if he contributed only 1 PK parameter value for 1 period to the statistical assessment.

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

Outcome measures

Outcome measures
Measure	Nintedanib 1 X 100 mg (R) n=19 Participants This arm includes all participants who were administered once 1 soft gelatin capsule of 100 milligram (mg) of nintedanib (reference treatment (R)) orally with 240 milliliter (mL) of water after breakfast.	Nintedanib 4 X 25 mg (T) n=19 Participants This arm includes all participants who were administered one single intake of 4 soft gelatin capsules of 25 mg of nintedanib (total administered dose = 100 mg) (test treatment (T)) orally with 240 milliliter (mL) of water after breakfast.
Area Under the Concentration-time Curve of the Nintedanib in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)	150.65 hours (h) *nanogram(ng)/milliliter (mL) Standard Error NA Standard error is actually adjusted geometric standard error. Adjusted geometric standard error=1.07.	148.34 hours (h) *nanogram(ng)/milliliter (mL) Standard Error NA Standard error is actually adjusted geometric standard error. Adjusted geometric standard error=1.07.

PRIMARY outcome

Timeframe: For both arms: Within 3 hours (h) before and 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h, 34 h, 48 h and 72h after nintedanib administration.

Maximum measured concentration of nintedanib in plasma (Cmax) is reported.

Outcome measures

Outcome measures
Measure	Nintedanib 1 X 100 mg (R) n=19 Participants This arm includes all participants who were administered once 1 soft gelatin capsule of 100 milligram (mg) of nintedanib (reference treatment (R)) orally with 240 milliliter (mL) of water after breakfast.	Nintedanib 4 X 25 mg (T) n=19 Participants This arm includes all participants who were administered one single intake of 4 soft gelatin capsules of 25 mg of nintedanib (total administered dose = 100 mg) (test treatment (T)) orally with 240 milliliter (mL) of water after breakfast.
Maximum Measured Concentration of Nintedanib in Plasma (Cmax)	15.23 nanogram (ng)/milliliter (mL) Standard Deviation NA Standard error is actually adjusted geometric standard error. Adjusted geometric standard error=1.11.	15.27 nanogram (ng)/milliliter (mL) Standard Deviation NA Standard error is actually adjusted geometric standard error. Adjusted geometric standard error=1.11.

SECONDARY outcome

Timeframe: For both arms: Within 3 hours (h) before and 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h, 34 h, 48 h and 72h after nintedanib administration.

Area under the concentration-time curve of nintedanib in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported.

Outcome measures

Outcome measures
Measure	Nintedanib 1 X 100 mg (R) n=19 Participants This arm includes all participants who were administered once 1 soft gelatin capsule of 100 milligram (mg) of nintedanib (reference treatment (R)) orally with 240 milliliter (mL) of water after breakfast.	Nintedanib 4 X 25 mg (T) n=19 Participants This arm includes all participants who were administered one single intake of 4 soft gelatin capsules of 25 mg of nintedanib (total administered dose = 100 mg) (test treatment (T)) orally with 240 milliliter (mL) of water after breakfast.
Area Under the Concentration-time Curve of Nintedanib in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	157.55 hours * nanogram/milliliter Standard Error NA Standard error is actually adjusted geometric standard error. Adjusted geometric standard error=1.07.	155.85 hours * nanogram/milliliter Standard Error NA Standard error is actually adjusted geometric standard error. Adjusted geometric standard error=1.07.

Adverse Events

Nintedanib 1 X 100 mg (R)

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Nintedanib 4 X 25 mg (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

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Nintedanib 1 X 100 mg (R) n=19 participants at risk This arm includes all participants who were administered once 1 soft gelatin capsule of of 100 milligram (mg) of nintedanib (reference treatment (R)) orally with 240 milliliter (mL) of water after breakfast.	Nintedanib 4 X 25 mg (T) n=19 participants at risk This arm includes all participants who were administered one single intake of 4 soft gelatin capsules of 25 mg of nintedanib (total administered dose = 100 mg) (test treatment (T)) orally with 240 milliliter (mL) of water after breakfast.
Gastrointestinal disorders Abdominal pain	10.5% 2/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.	0.00% 0/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.
Gastrointestinal disorders Abdominal pain upper	10.5% 2/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.	5.3% 1/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.
Gastrointestinal disorders Constipation	0.00% 0/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.	5.3% 1/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.
Gastrointestinal disorders Diarrhoea	15.8% 3/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.	21.1% 4/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.
Gastrointestinal disorders Flatulence	5.3% 1/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.	0.00% 0/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.
Gastrointestinal disorders Gastritis	5.3% 1/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.	0.00% 0/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.
Gastrointestinal disorders Nausea	10.5% 2/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.	5.3% 1/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.
Infections and infestations Nasopharyngitis	5.3% 1/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.	0.00% 0/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.
Injury, poisoning and procedural complications Sunburn	5.3% 1/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.	0.00% 0/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.
Metabolism and nutrition disorders Decreased appetite	5.3% 1/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.	0.00% 0/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.
Nervous system disorders Dizziness	5.3% 1/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.	0.00% 0/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.
Nervous system disorders Headache	5.3% 1/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.	0.00% 0/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.3% 1/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.	0.00% 0/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.
Skin and subcutaneous tissue disorders Macule	5.3% 1/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.	0.00% 0/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.
Skin and subcutaneous tissue disorders Pruritus	5.3% 1/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.	0.00% 0/19 • For both arms: From drug administration until 14 days thereafter. Treated set (TS): TS included all subjects who were randomised and treated with at least 1 dose of the investigational medicinal product.