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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-000690-39 | EudraCT Number | EudraCT |
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The primary objective of this study is to investigate the effect of mild (Child-Pugh A, score 5-6) and moderate (Child-Pugh B, score 7-9) hepatic impairment on the pharmacokinetics, safety and tolerability of nintedanib, in comparison with a control group with normal hepatic function following oral administration of nintedanib as single dose.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mild liver impairment | Experimental | Patients with mild hepatic impaired function (Child-Pugh A) |
|
| Moderate liver impairment | Experimental | Patients with moderate hepatic impaired function (Child-Pugh B) |
|
| Healthy volunteers | Experimental | Healthy control subjects |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nintedanib | Drug | Soft gelatine capsule |
| |
| Nintedanib |
| Measure | Description | Time Frame |
|---|---|---|
| AUC (0-inf) of Nintedanib | AUC (0-inf) (Area under the concentration-time curve of the Nintedanib in plasma over the time interval from 0 extrapolated to infinity) | 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 |
| Cmax of Nintedanib | Cmax (Maximum measured concentration of the Nintedanib in plasma) | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| AUC (0-tz) of Nintedanib | 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) | 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 |
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Inclusion criteria:
Healthy subjects:
Hepatically impaired patients as determined by a hepatologist/ gastroenterologist:
Exclusion criteria:
Healthy subjects:
Hepatically impaired patients as determined by a hepatologist/gastroenterologist:
Medical disorder, condition or history of such that would impair the patient's ability to participate or complete this study in the opinion of the investigator or the sponsor
Patients with significant diseases other than underlying diagnose of hepatic impairment and concomitant diseases related to it. A significant disease is defined as a disease which in the opinion of the investigator:
Surgery of the gastrointestinal tract that could interfere with the kinetics of the trial medication based on the investigator´s judgment
Women who are breast feeding or of child-bearing potential not using a highly effective method of birth control for at least one month prior to inclusion and at least 3 month after administration of trial medication
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1199.200.49001 Boehringer Ingelheim Investigational Site | Kiel | Germany |
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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).
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Treated set: The treated set (TS) included all subjects who were dispensed study medication and were documented to have taken atleast one dose of investigational treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | AUC (0-inf) of Nintedanib | AUC (0-inf) (Area under the concentration-time curve of the Nintedanib in plasma over the time interval from 0 extrapolated to infinity) | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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 |
|
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
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim | 800-243-0127 | +1 | clintriage.rdg@boehringer-ingelheim.com |
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| ID | Term |
|---|---|
| D048550 | Hepatic Insufficiency |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C530716 | nintedanib |
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| Drug |
Soft gelatine capsule |
|
| Nintedanib | Drug | Soft gelatine capsule |
|
| Number (%) of Subjects With Drug-related Adverse Events (AEs) |
Number (%) of subjects with drug-related Adverse events (AEs) |
| (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 |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 |
| 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). |
| OG002 | Healthy Matched Child-Pugh A | 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 |
| OG003 | 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 . |
|
|
|
| Primary | Cmax of Nintedanib | Cmax (Maximum measured concentration of the Nintedanib in plasma) | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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 |
|
|
|
|
| Secondary | AUC (0-tz) of Nintedanib | 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) | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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 |
|
|
|
|
| Secondary | Number (%) of Subjects With Drug-related Adverse Events (AEs) | Number (%) of subjects with drug-related Adverse events (AEs) | TS | Posted | Number | percentage of participants | (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 |
| 8 |
| 0 |
| 8 |
| EG001 | 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). | 0 | 8 | 3 | 8 |
| EG002 | 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. | 0 | 17 | 3 | 17 |
| Nausea | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
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
| Superiority or Other |
| The statistical model used for the analysis of Cmax was an ANOVA (analysis of variance) model on the logarithmic scale. Observations from a subject with hepatic impairment and the matched healthy control subject were analysed as a matched pair. | ANOVA | Fixed effect: 'hepatic status'; indicated whether a subject with hepatic impairment or a healthy subject , Random effect: 'matched pair'. | Ratio of geometric means | 761.01 | Standard Deviation | 69.1 | 2-Sided | 90 | 439.01 | 1319.18 | Ratio of Child Pugh B (Test): Healthy Child Pugh B (Reference). The Standard deviation is the Intra-individual gCV | No | Superiority or Other |
| Superiority or Other |
| The statistical model used for the analysis of AUC (0-tz) was an ANOVA (analysis of variance) model on the logarithmic scale. Observations from a subject with hepatic impairment and the matched healthy control subject were analysed as a matched pair. | ANOVA | Fixed effect: 'hepatic status'; indicated whether a subject with hepatic impairment or a healthy subject , Random effect: 'matched pair'. | Ratio of geometric means | 870.74 | Standard Deviation | 45.7 | 2-Sided | 90 | 576.36 | 1315.49 | Ratio of Child Pugh B (Test): Healthy Child Pugh B (Reference). The Standard deviation is the Intra-individual gCV | No | Superiority or Other |