Trial Outcomes & Findings for Relative Bioavailability of 2 Oral Formulations of Nintedanib (NCT NCT02572752)

Last Updated: 2017-01-05

Results Overview

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). The unadjusted geometric mean (gMean) and geometric coefficient variation (gCV) was calculated for Test treatment (T), Reference treatment 1 (R1) and Reference treatment 2 (R2) separately.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

70 participants

Primary outcome timeframe

-1:00 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 4:30h, 5:00h, 5:30h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration.

Results posted on

2017-01-05

Participant Flow

The trial was randomised and open-label with a 3-way crossover design (2 administrations of reference treatment and 1 administration of test treatment in all subjects). In this study 70 subjects were entered and treated.

Participant milestones

Participant milestones
Measure	Nin 2x100 mg(R1) / Nin 2x100 mg(R2) / Nin 1x200 mg(T) Subjects were treated with single oral dose, started in Period 1 (Reference treatment (R1)) and Period 2 (Reference treatment (R2)) with nintedanib (nin) soft gelatine capsule, 200 mg (2x100 mg) with about 240 mL of water, followed in Period 3 (Test treatment (T)) with nintedanib soft gelatine capsule, 200 mg (1x200mg) with about 240 mL of water. Treatment periods were separated by a wash-out phase of at least 12 days.	Nin 2x100 mg(R1) / Nin 1x200 mg(T) / Nin 2x100 mg(R2) Subjects were treated with single oral dose, started in Period 1 (Reference treatment (R1)) with nintedanib soft gelatine capsule, 200 mg (2x100mg) with about 240 mL of water, followed in Period 2 (Test treatment (T)) with nintedanib soft gelatine capsule, 200 mg (1x200mg) with about 240 mL of water and in Period 3 (Reference treatment (R2)) with nintedanib soft gelatine capsule, 200 mg (2x100mg) with about 240 mL of water. Treatment periods were separated by a wash-out phase of at least 12 days.	Nin 1x200 mg(T) / Nin 2x100 mg(R1) / Nin 2x100 mg(R2) Subjects were treated with single oral dose, started in Period 1 (Test treatment (T)) with nintedanib soft gelatine capsule, 200 mg (1x200mg) with about 240 mL of water, followed in Period 2 (Reference treatment (R1)) and Period 3 (Reference treatment (R2)) with nintedanib soft gelatine capsule, 200 mg (2x100 mg) with about 240 mL of water. Treatment periods were separated by a wash-out phase of at least 12 days.
Period 1 Including Washout STARTED	23	23	24
Period 1 Including Washout COMPLETED	23	23	24
Period 1 Including Washout NOT COMPLETED	0	0	0
Period 2 Including Washout STARTED	23	23	24
Period 2 Including Washout COMPLETED	23	23	24
Period 2 Including Washout NOT COMPLETED	0	0	0
Period 3 Including Washout STARTED	23	23	24
Period 3 Including Washout COMPLETED	23	23	24
Period 3 Including Washout NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Relative Bioavailability of 2 Oral Formulations of Nintedanib

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nin 2x100 mg(R1) / Nin 2x100 mg(R2) / Nin 1x200 mg(T) n=23 Participants Subjects were treated with single oral dose, started in Period 1 (Reference treatment (R1)) and Period 2 (Reference treatment (R2)) with nintedanib (nin) soft gelatine capsule, 200 mg (2x100 mg) with about 240 mL of water, followed in Period 3 (Test treatment (T)) with nintedanib soft gelatine capsule, 200 mg (1x200mg) with about 240 mL of water. Treatment periods were separated by a wash-out phase of at least 12 days.	Nin 2x100 mg(R1) / Nin 1x200 mg(T) / Nin 2x100 mg(R2) n=23 Participants Subjects were treated with single oral dose, started in Period 1 (Reference treatment (R1)) with nintedanib soft gelatine capsule, 200 mg (2x100mg) with about 240 mL of water, followed in Period 2 (Test treatment (T)) with nintedanib soft gelatine capsule, 200 mg (1x200mg) with about 240 mL of water and in Period 3 (Reference treatment (R2)) with nintedanib soft gelatine capsule, 200 mg (2x100mg) with about 240 mL of water. Treatment periods were separated by a wash-out phase of at least 12 days.	Nin 1x200 mg(T) / Nin 2x100 mg(R1) / Nin 2x100 mg(R2) n=24 Participants Subjects were treated with single oral dose, started in Period 1 (Test treatment (T)) with nintedanib soft gelatine capsule, 200 mg (1x200mg) with about 240 mL of water, followed in Period 2 (Reference treatment (R1)) and Period 3 (Reference treatment (R2)) with nintedanib soft gelatine capsule, 200 mg (2x100 mg) with about 240 mL of water. Treatment periods were separated by a wash-out phase of at least 12 days.	Total n=70 Participants Total of all reporting groups
Age, Continuous	34.0 Years STANDARD_DEVIATION 10.3 • n=93 Participants	36.6 Years STANDARD_DEVIATION 9.5 • n=4 Participants	31.6 Years STANDARD_DEVIATION 7.2 • n=27 Participants	34.0 Years STANDARD_DEVIATION 9.2 • n=483 Participants
Gender Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Gender Male	23 Participants n=93 Participants	23 Participants n=4 Participants	24 Participants n=27 Participants	70 Participants n=483 Participants

PRIMARY outcome

Timeframe: -1:00 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 4:30h, 5:00h, 5:30h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration.

Population: Pharmacokinetic Set (PKS) : This analysis set included all treated subjects who provided at least 1 observation for at least 1 primary endpoint, and who had no important protocol violations impacting statistical evaluation of PK endpoints.

Outcome measures

Outcome measures
Measure	Nintedanib, Test Treatment (T) n=70 Participants Subjects were treated with single oral dose, started in Period 1 (Test treatment (T)) with nintedanib soft gelatine capsule, 200 mg (1x200mg) with about 240 mL of water.	Nintedanib, Reference Treatment (R1) n=70 Participants Subjects were treated with single oral dose, started in Period 1 (Reference treatment (R1)) with nintedanib soft gelatine capsule, 200 mg (2x100mg) with about 240 mL of water.	Nintedanib, Reference Treatment (R2) n=70 Participants Subjects were treated with single oral dose, started in Period 1 (Reference treatment (R2)) with nintedanib soft gelatine capsule, 200 mg (2x100mg) with about 240 mL of water.
AUC0-tz	300 ng*h/mL Geometric Coefficient of Variation 38.8	310 ng*h/mL Geometric Coefficient of Variation 37.6	306 ng*h/mL Geometric Coefficient of Variation 36.2

PRIMARY outcome

Population: PKS

Maximum measured concentration of the analyte in plasma (Cmax). The unadjusted geometric mean (gMean) and geometric coefficient variation (gCV) was calculated for Test treatment (T), Reference 1 treatment (R1) and Reference 2 treatment (R2) separately.

Outcome measures

Outcome measures
Measure	Nintedanib, Test Treatment (T) n=70 Participants Subjects were treated with single oral dose, started in Period 1 (Test treatment (T)) with nintedanib soft gelatine capsule, 200 mg (1x200mg) with about 240 mL of water.	Nintedanib, Reference Treatment (R1) n=70 Participants Subjects were treated with single oral dose, started in Period 1 (Reference treatment (R1)) with nintedanib soft gelatine capsule, 200 mg (2x100mg) with about 240 mL of water.	Nintedanib, Reference Treatment (R2) n=70 Participants Subjects were treated with single oral dose, started in Period 1 (Reference treatment (R2)) with nintedanib soft gelatine capsule, 200 mg (2x100mg) with about 240 mL of water.
Cmax	39.3 ng/mL Geometric Coefficient of Variation 56.0	41.1 ng/mL Geometric Coefficient of Variation 43.4	39.8 ng/mL Geometric Coefficient of Variation 46.3

SECONDARY outcome

Population: PKS

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf). The unadjusted geometric mean (gMean) and geometric coefficient variation (gCV) was calculated for Test treatment (T), Reference 1 treatment (R1) and Reference 2 treatment (R2) separately.

Outcome measures

Outcome measures
Measure	Nintedanib, Test Treatment (T) n=70 Participants Subjects were treated with single oral dose, started in Period 1 (Test treatment (T)) with nintedanib soft gelatine capsule, 200 mg (1x200mg) with about 240 mL of water.	Nintedanib, Reference Treatment (R1) n=70 Participants Subjects were treated with single oral dose, started in Period 1 (Reference treatment (R1)) with nintedanib soft gelatine capsule, 200 mg (2x100mg) with about 240 mL of water.	Nintedanib, Reference Treatment (R2) n=70 Participants Subjects were treated with single oral dose, started in Period 1 (Reference treatment (R2)) with nintedanib soft gelatine capsule, 200 mg (2x100mg) with about 240 mL of water.
AUC0-inf	311 ng*h/mL Geometric Coefficient of Variation 38.8	322 ng*h/mL Geometric Coefficient of Variation 37.7	319 ng*h/mL Geometric Coefficient of Variation 36.4

Adverse Events

Nintedanib, Test Treatment (T)

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Nintedanib, Reference Treatment (R1 & R2)

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Nintedanib, Test Treatment (T) n=70 participants at risk Subjects were treated with single oral dose of nintedanib soft gelatine capsule (Test treatment (T)) , 200 mg (1x200mg) with about 240 mL of water.	Nintedanib, Reference Treatment (R1 & R2) n=70 participants at risk Subjects were treated twice with single oral dose of nintedanib soft gelatine capsule (Reference treatment (R1 \& R2)), 200 mg (2x100mg) with about 240 mL of water.
Gastrointestinal disorders Diarrhoea	22.9% 16/70 • From first drug administration until 12 days after the last drug administration of nintedanib, ie., upto 16 days.	28.6% 20/70 • From first drug administration until 12 days after the last drug administration of nintedanib, ie., upto 16 days.
Gastrointestinal disorders Nausea	5.7% 4/70 • From first drug administration until 12 days after the last drug administration of nintedanib, ie., upto 16 days.	8.6% 6/70 • From first drug administration until 12 days after the last drug administration of nintedanib, ie., upto 16 days.
Infections and infestations Nasopharyngitis	2.9% 2/70 • From first drug administration until 12 days after the last drug administration of nintedanib, ie., upto 16 days.	5.7% 4/70 • From first drug administration until 12 days after the last drug administration of nintedanib, ie., upto 16 days.
Nervous system disorders Headache	10.0% 7/70 • From first drug administration until 12 days after the last drug administration of nintedanib, ie., upto 16 days.	10.0% 7/70 • From first drug administration until 12 days after the last drug administration of nintedanib, ie., upto 16 days.

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