Trial Outcomes & Findings for Nintedanib in Volunteers With Hepatic Impairment Compared With Healthy Volunteers (NCT NCT02191865)
NCT ID: NCT02191865
Last Updated: 2016-02-01
Results Overview
AUC (0-inf) (Area under the concentration-time curve of the Nintedanib in plasma over the time interval from 0 extrapolated to infinity)
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
33 participants
Primary outcome timeframe
Pre-dose and 1 hour (h), 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h and 168h after drug administration
Results posted on
2016-02-01
Participant Flow
Healthy subjects were to be matched to subjects with hepatic impairment ((Child-Pugh A, score 5 or 6),(Child-Pugh B, score 7 to 9)) by age (±10 years), body weight (±10%), sex, race, and smoking habits (current vs. ex- and never smokers).
Participant milestones
| Measure |
Child Pugh A
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in patients with mild hepatic impairment (Child-Pugh A).
Subjects were dosed in a 3 plus 5 design, where a subgroup of 3 subjects was dosed and safety was evaluated formally at a safety meeting prior to dosing the remaining 5 subjects in the group.
|
Child Pugh B
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in patients with moderate hepatic impairment (Child-Pugh B).
Subjects were dosed in a 3 plus 5 design, where a subgroup of 3 subjects was dosed and safety was evaluated formally at a safety meeting prior to dosing the remaining 5 subjects in the group.
|
Healthy
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in subjects with normal hepatic function.
|
|---|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
17
|
|
Overall Study
COMPLETED
|
8
|
8
|
17
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Nintedanib in Volunteers With Hepatic Impairment Compared With Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Child Pugh A
n=8 Participants
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in patients with mild hepatic impairment (Child-Pugh A).
Subjects were dosed in a 3 plus 5 design, where a subgroup of 3 subjects was dosed and safety was evaluated formally at a safety meeting prior to dosing the remaining 5 subjects in the group.
|
Child Pugh B
n=8 Participants
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in patients with moderate hepatic impairment (Child-Pugh B).
Subjects were dosed in a 3 plus 5 design, where a subgroup of 3 subjects was dosed and safety was evaluated formally at a safety meeting prior to dosing the remaining 5 subjects in the group.
|
Healthy
n=17 Participants
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in subjects with normal hepatic function.
|
Total
n=33 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
60.6 years
STANDARD_DEVIATION 8.1 • n=5 Participants
|
56.6 years
STANDARD_DEVIATION 6.5 • n=7 Participants
|
57.6 years
STANDARD_DEVIATION 8.4 • n=5 Participants
|
58.1 years
STANDARD_DEVIATION 7.8 • n=4 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
20 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Pre-dose and 1 hour (h), 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h and 168h after drug administrationPopulation: Pharmacokinetic set (PKS): The PKS included all subjects of the TS who provided at least 1 observation for at least 1 primary PK endpoint, which was judged as PK evaluable and was not affected by important protocol violation(s) relevant to the evaluation of PK.
AUC (0-inf) (Area under the concentration-time curve of the Nintedanib in plasma over the time interval from 0 extrapolated to infinity)
Outcome measures
| Measure |
Child-Pugh A
n=8 Participants
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in patients with mild hepatic impairment (Child-Pugh A).
|
Child-Pugh B
n=8 Participants
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in patients with moderate hepatic impairment (Child-Pugh B).
|
Healthy Matched Child-Pugh A
n=8 Participants
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in healthy control subjects matched with hepatic (Child pugh A) impaired subjects
|
Healthy Matched Child-Pugh B
n=8 Participants
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in healthy control subjects matched with hepatic (Child pugh B) impaired subjects .
|
|---|---|---|---|---|
|
AUC (0-inf) of Nintedanib
|
200 ng*h/mL
Geometric Coefficient of Variation 87.7
|
674 ng*h/mL
Geometric Coefficient of Variation 66.3
|
92.7 ng*h/mL
Geometric Coefficient of Variation 58.5
|
77.8 ng*h/mL
Geometric Coefficient of Variation 38.2
|
PRIMARY outcome
Timeframe: Pre-dose and 1 hour (h), 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h and 168h after drug administrationPopulation: Pharmacokinetic set (PKS): The PKS included all subjects of the TS who provided at least 1 observation for at least 1 primary PK endpoint, which was judged as PK evaluable and was not affected by important protocol violation(s) relevant to the evaluation of PK.
Cmax (Maximum measured concentration of the Nintedanib in plasma)
Outcome measures
| Measure |
Child-Pugh A
n=8 Participants
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in patients with mild hepatic impairment (Child-Pugh A).
|
Child-Pugh B
n=8 Participants
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in patients with moderate hepatic impairment (Child-Pugh B).
|
Healthy Matched Child-Pugh A
n=8 Participants
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in healthy control subjects matched with hepatic (Child pugh A) impaired subjects
|
Healthy Matched Child-Pugh B
n=8 Participants
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in healthy control subjects matched with hepatic (Child pugh B) impaired subjects .
|
|---|---|---|---|---|
|
Cmax of Nintedanib
|
20.5 ng/mL
Geometric Coefficient of Variation 68.4
|
59.4 ng/mL
Geometric Coefficient of Variation 87.0
|
9.25 ng/mL
Geometric Coefficient of Variation 54.1
|
7.81 ng/mL
Geometric Coefficient of Variation 49.3
|
SECONDARY outcome
Timeframe: Pre-dose and 1 hour (h), 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h and 168h after drug administrationPopulation: Pharmacokinetic set (PKS): The PKS included all subjects of the TS who provided at least 1 observation for at least 1 primary PK endpoint, which was judged as PK evaluable and was not affected by important protocol violation(s) relevant to the evaluation of PK.
AUC (0-tz) (Area under the concentration-time curve of the Nintedanib in plasma over the time interval from 0 to the last quantifiable drug plasma concentration)
Outcome measures
| Measure |
Child-Pugh A
n=8 Participants
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in patients with mild hepatic impairment (Child-Pugh A).
|
Child-Pugh B
n=8 Participants
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in patients with moderate hepatic impairment (Child-Pugh B).
|
Healthy Matched Child-Pugh A
n=8 Participants
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in healthy control subjects matched with hepatic (Child pugh A) impaired subjects
|
Healthy Matched Child-Pugh B
n=8 Participants
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in healthy control subjects matched with hepatic (Child pugh B) impaired subjects .
|
|---|---|---|---|---|
|
AUC (0-tz) of Nintedanib
|
193 ng*h/mL
Geometric Coefficient of Variation 89.5
|
652 ng*h/mL
Geometric Coefficient of Variation 66.2
|
89.2 ng*h/mL
Geometric Coefficient of Variation 59.6
|
74.8 ng*h/mL
Geometric Coefficient of Variation 38.9
|
SECONDARY outcome
Timeframe: (AEs) during the 'on-treatment' period (from administration of trial medication until the end of the 28-day residual effect period); Up to 29 daysPopulation: TS
Number (%) of subjects with drug-related Adverse events (AEs)
Outcome measures
| Measure |
Child-Pugh A
n=8 Participants
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in patients with mild hepatic impairment (Child-Pugh A).
|
Child-Pugh B
n=8 Participants
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in patients with moderate hepatic impairment (Child-Pugh B).
|
Healthy Matched Child-Pugh A
n=17 Participants
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in healthy control subjects matched with hepatic (Child pugh A) impaired subjects
|
Healthy Matched Child-Pugh B
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in healthy control subjects matched with hepatic (Child pugh B) impaired subjects .
|
|---|---|---|---|---|
|
Number (%) of Subjects With Drug-related Adverse Events (AEs)
|
0.0 percentage of participants
|
37.5 percentage of participants
|
17.6 percentage of participants
|
—
|
Adverse Events
Child Pugh A
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Child Pugh B
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Healthy
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Child Pugh A
n=8 participants at risk
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in patients with mild hepatic impairment (Child-Pugh A).
|
Child Pugh B
n=8 participants at risk
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in patients with moderate hepatic impairment (Child-Pugh B).
|
Healthy
n=17 participants at risk
Oral administration of 1 soft gelatin capsule of Nintedanib 100 mg with 240 ml of water under fed conditions in subjects with normal hepatic function.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/8 • AEs during the 'on-treatment' period (from administration of trial medication until the end of the 28-day residual effect period); up to 29 days
|
12.5%
1/8 • AEs during the 'on-treatment' period (from administration of trial medication until the end of the 28-day residual effect period); up to 29 days
|
0.00%
0/17 • AEs during the 'on-treatment' period (from administration of trial medication until the end of the 28-day residual effect period); up to 29 days
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/8 • AEs during the 'on-treatment' period (from administration of trial medication until the end of the 28-day residual effect period); up to 29 days
|
12.5%
1/8 • AEs during the 'on-treatment' period (from administration of trial medication until the end of the 28-day residual effect period); up to 29 days
|
11.8%
2/17 • AEs during the 'on-treatment' period (from administration of trial medication until the end of the 28-day residual effect period); up to 29 days
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/8 • AEs during the 'on-treatment' period (from administration of trial medication until the end of the 28-day residual effect period); up to 29 days
|
0.00%
0/8 • AEs during the 'on-treatment' period (from administration of trial medication until the end of the 28-day residual effect period); up to 29 days
|
5.9%
1/17 • AEs during the 'on-treatment' period (from administration of trial medication until the end of the 28-day residual effect period); up to 29 days
|
|
Nervous system disorders
Headache
|
0.00%
0/8 • AEs during the 'on-treatment' period (from administration of trial medication until the end of the 28-day residual effect period); up to 29 days
|
0.00%
0/8 • AEs during the 'on-treatment' period (from administration of trial medication until the end of the 28-day residual effect period); up to 29 days
|
5.9%
1/17 • AEs during the 'on-treatment' period (from administration of trial medication until the end of the 28-day residual effect period); up to 29 days
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/8 • AEs during the 'on-treatment' period (from administration of trial medication until the end of the 28-day residual effect period); up to 29 days
|
12.5%
1/8 • AEs during the 'on-treatment' period (from administration of trial medication until the end of the 28-day residual effect period); up to 29 days
|
0.00%
0/17 • AEs during the 'on-treatment' period (from administration of trial medication until the end of the 28-day residual effect period); up to 29 days
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
0.00%
0/8 • AEs during the 'on-treatment' period (from administration of trial medication until the end of the 28-day residual effect period); up to 29 days
|
12.5%
1/8 • AEs during the 'on-treatment' period (from administration of trial medication until the end of the 28-day residual effect period); up to 29 days
|
0.00%
0/17 • AEs during the 'on-treatment' period (from administration of trial medication until the end of the 28-day residual effect period); up to 29 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights
- Publication restrictions are in place
Restriction type: OTHER