Trial Outcomes & Findings for Influence of Bosentan on the Pharmacokinetics of Nintedanib (NCT NCT02667704)
NCT ID: NCT02667704
Last Updated: 2017-04-13
Results Overview
Area under the concentration-time curve of Nintedanib in plasma over the time interval from 0 to the last quantifiable concentration (AUC0-tz). PK plasma samples were taken at: 1 hour (h) before drug administration (approximate time for predose sample) and 30 minutes, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 144.5h, 145h, 145.5h, 146h, 146.5h, 147h, 148h, 149h, 150h, 152h, 154h, 156h, 168h, 180h, 192h, 216h after drug administration. Two different visits; Visit 2 (R): -1 to 72 h, Visit 3 (T) 144 to 216 h. AUC0-tz was calculated for each visit separately.
COMPLETED
PHASE1
13 participants
Up to 216 hours. The details are mentioned in description.
2017-04-13
Participant Flow
This is open-label, mono-center clinical trial in healthy male subjects applied a fixed sequence, two-treatment, two- period crossover design. All subjects were to undergo 2 trial periods in a fixed sequence, receiving reference treatment (R) in Period 1, and test treatment (T) in Period 2. A wash-out between Periods 1 and 2 was not mandatory.
Participant milestones
| Measure |
Nintedanib (Reference (R)) / Bosentan+Nintedanib (Test (T))
Subject received single dose of 150 milligram (mg) Nintedanib (1 x 1 soft gelatin capsule) on day 1 of period 1 and then multiple doses of 250 mg Bosentan (2 x 1 film-coated tablets) on days 1 to 8 of period 2 plus single dose of 150 milligram (mg) Nintedanib (1 x 1 soft gelatin capsule) on day 7 of period 2 administered orally with 240 millilitre (mL) of water
|
|---|---|
|
Treatment Period 1
STARTED
|
13
|
|
Treatment Period 1
COMPLETED
|
13
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
|
Treatment Period 2
STARTED
|
13
|
|
Treatment Period 2
COMPLETED
|
13
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Influence of Bosentan on the Pharmacokinetics of Nintedanib
Baseline characteristics by cohort
| Measure |
Nintedanib (Reference (R)) / Bosentan+Nintedanib (Test (T))
n=13 Participants
Subject received single dose of 150 milligram (mg) Nintedanib (1 x 1 soft gelatin capsule) on day 1 of period 1 and then multiple doses of 250 mg Bosentan (2 x 1 film-coated tablets) on days 1 to 8 of period 2 plus single dose of 150 milligram (mg) Nintedanib (1 x 1 soft gelatin capsule) on day 7 of period 2 administered orally with 240 millilitre (mL) of water
|
|---|---|
|
Age, Continuous
|
35.0 Years
STANDARD_DEVIATION 9.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 216 hours. The details are mentioned in description.Population: Pharmacokinetic parameter analysis set (PKS): all subjects in the treated set who provided at least one primary or secondary pharmacokinetic (PK) parameter not flagged for exclusion due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.
Area under the concentration-time curve of Nintedanib in plasma over the time interval from 0 to the last quantifiable concentration (AUC0-tz). PK plasma samples were taken at: 1 hour (h) before drug administration (approximate time for predose sample) and 30 minutes, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 144.5h, 145h, 145.5h, 146h, 146.5h, 147h, 148h, 149h, 150h, 152h, 154h, 156h, 168h, 180h, 192h, 216h after drug administration. Two different visits; Visit 2 (R): -1 to 72 h, Visit 3 (T) 144 to 216 h. AUC0-tz was calculated for each visit separately.
Outcome measures
| Measure |
Nintedanib (R)
n=13 Participants
Subject received single dose of 150 milligram (mg) Nintedanib (1 x 1 soft gelatin capsule) on day 1 administered orally with 240 millilitre (mL) of water.
|
Bosentan+Nintedanib (T)
n=13 Participants
Subject received multiple doses of 250 mg Bosentan (2 x 1 film-coated tablets) on days 1 to 8 plus single dose of 150 milligram (mg) Nintedanib (1 x 1 soft gelatin capsule) on day 7 administered orally with 240 mL of water
|
|---|---|---|
|
Area Under the Concentration-time Curve of Nintedanib in Plasma Over the Time Interval From 0 to the Last Quantifiable Concentration (AUC0-tz)
|
195 nanogram (ng)*hour (h) /millilitre (mL)
Geometric Coefficient of Variation 38.8
|
193 nanogram (ng)*hour (h) /millilitre (mL)
Geometric Coefficient of Variation 33.4
|
PRIMARY outcome
Timeframe: Up to 216 hours. The details are mentioned in description.Population: Pharmacokinetic parameter analysis set (PKS): all subjects in the treated set who provided at least one primary or secondary pharmacokinetic (PK) parameter not flagged for exclusion due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.
Maximum measured concentration of Nintedanib in plasma (Cmax). PK plasma samples were taken at: 1 hour (h) before drug administration and 30 minutes, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 144.5h, 145h, 145.5h, 146h, 146.5h, 147h, 148h, 149h, 150h, 152h, 154h, 156h, 168h, 180h, 192h, 216h after drug administration. Two different visits; Visit 2 (R): -1 to 72 h, Visit 3 (T) 144 to 216 h. Cmax was determined for each visit separately.
Outcome measures
| Measure |
Nintedanib (R)
n=13 Participants
Subject received single dose of 150 milligram (mg) Nintedanib (1 x 1 soft gelatin capsule) on day 1 administered orally with 240 millilitre (mL) of water.
|
Bosentan+Nintedanib (T)
n=13 Participants
Subject received multiple doses of 250 mg Bosentan (2 x 1 film-coated tablets) on days 1 to 8 plus single dose of 150 milligram (mg) Nintedanib (1 x 1 soft gelatin capsule) on day 7 administered orally with 240 mL of water
|
|---|---|---|
|
Maximum Measured Concentration of Nintedanib in Plasma (Cmax)
|
21.9 ng/mL
Geometric Coefficient of Variation 55.2
|
22.7 ng/mL
Geometric Coefficient of Variation 42.2
|
SECONDARY outcome
Timeframe: Up to 216 hours. The details are mentioned in description.Population: Pharmacokinetic parameter analysis set (PKS): all subjects in the treated set who provided at least one primary or secondary pharmacokinetic (PK) parameter not flagged for exclusion due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.
Area under the concentration-time curve of Nintedanib in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity). PK plasma samples were taken at: 1 hour (h) before drug administration and 30 minutes, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 144.5h, 145h, 145.5h, 146h, 146.5h, 147h, 148h, 149h, 150h, 152h, 154h, 156h, 168h, 180h, 192h, 216h after drug administration. Two different visits; Visit 2 (R): -1 to 72 h, Visit 3 (T) 144 to 216 h. AUC0-infinity was calculated for each visit separately.
Outcome measures
| Measure |
Nintedanib (R)
n=13 Participants
Subject received single dose of 150 milligram (mg) Nintedanib (1 x 1 soft gelatin capsule) on day 1 administered orally with 240 millilitre (mL) of water.
|
Bosentan+Nintedanib (T)
n=13 Participants
Subject received multiple doses of 250 mg Bosentan (2 x 1 film-coated tablets) on days 1 to 8 plus single dose of 150 milligram (mg) Nintedanib (1 x 1 soft gelatin capsule) on day 7 administered orally with 240 mL of water
|
|---|---|---|
|
Area Under the Concentration-time Curve of Nintedanib in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity)
|
204 ng*h / mL
Geometric Coefficient of Variation 38.3
|
208 ng*h / mL
Geometric Coefficient of Variation 34.1
|
Adverse Events
Nintedanib (R)
Bosentan
Bosentan+Nintedanib (T)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Nintedanib (R)
n=13 participants at risk
Subject received single dose of 150 milligram (mg) Nintedanib (1 x 1 soft gelatin capsule) on day 1 of period 1 administered orally with 240 millilitre (mL) of water.
|
Bosentan
n=13 participants at risk
Subject received multiple doses of 250 mg Bosentan (2 x 1 film-coated tablets) on days 1 to 6 of period 2 administered orally with 240 mL of water
|
Bosentan+Nintedanib (T)
n=13 participants at risk
Subject received multiple doses of 250 mg Bosentan (2 x 1 film-coated tablets) on days 7 and 8 of period 2 plus single dose of 150 milligram (mg) Nintedanib (1 x 1 soft gelatin capsule) on day 7 administered orally with 240 mL of water
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
0.00%
0/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
7.7%
1/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
|
Infections and infestations
Herpes simplex
|
0.00%
0/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
7.7%
1/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
0.00%
0/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
|
Infections and infestations
Oral herpes
|
7.7%
1/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
0.00%
0/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
0.00%
0/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
|
Infections and infestations
Rhinitis
|
0.00%
0/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
0.00%
0/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
7.7%
1/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
|
Nervous system disorders
Dizziness
|
7.7%
1/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
0.00%
0/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
0.00%
0/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
|
Nervous system disorders
Headache
|
15.4%
2/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
7.7%
1/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
0.00%
0/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
7.7%
1/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
0.00%
0/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
7.7%
1/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
0.00%
0/13 • From first drug administration until 13 days after the last drug administration, up to 21 days
|
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER