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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-001009-26 | EudraCT Number | EudraCT |
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The objective of the current study is to investigate the relative bioavailability of a single dose of nintedanib low or high dose with and without coadministration of ketoconazole at steady state
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 Nintedanib (Reference) | Experimental | single dose, oral with 240 ml water |
|
| 2 Nintedanib + Ketoconazole (Test) | Experimental | Nintedanib single dose, Ketoconazole steady state, oral with 240 ml water |
|
| 3 Nintedanib (Reference) | Experimental | single dose, oral with 240 ml water |
|
| 4 Nintedanib + Ketoconazole (Test) | Experimental | Nintedanib single dose, Ketoconazole steady state, oral with 240 ml water |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nintedanib | Drug | low or medium dose depending on pilot part |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve From 0 Extrapolated to Infinity (AUC0-∞) | AUC0-∞ represents the Area under the concentration-time curve of nintedanib in plasma over the time interval from 0 extrapolated to infinity For this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities | 1 hour (h) before drug administration and 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h and 72h after the drug administration |
| Maximum Measured Concentration (Cmax) | Cmax represents the maximum concentration of nintedanib in plasma For this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities | 1 hour (h) before drug administration and 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h and 72h after the drug administration |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve From 0 to the Last Quantifiable Concentration (AUC0-tz) | AUC0-tz represents the area under the plasma concentration-time curve of nintedanib from time 0 to the last quantifiable nintedanib plasma concentration. For this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities | 1 hour (h) before drug administration and 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h and 72h after the drug administration |
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Inclusion criteria:
1. healthy male subjects
Exclusion criteria:
1. Any relevant deviation from healthy conditions
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1199.161.1 Boehringer Ingelheim Investigational Site | Biberach | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29500603 | Derived | Luedtke D, Marzin K, Jungnik A, von Wangenheim U, Dallinger C. Effects of Ketoconazole and Rifampicin on the Pharmacokinetics of Nintedanib in Healthy Subjects. Eur J Drug Metab Pharmacokinet. 2018 Oct;43(5):533-541. doi: 10.1007/s13318-018-0467-9. |
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This was a randomised, open-label trial with a 2-way cross-over Pilot part, followed by a 2-way cross-over Main part. Subjects participated either in the Pilot part with 2 treatment sequences (A_B and B_A) or in the Main part with treatment sequences (C_D and D_C) with wash-out period of at least 14 days between each sequence.
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| ID | Title | Description |
|---|---|---|
| FG000 | Nintedanib (Pilot Part)/ Nintedanib+Ketoconazole (Pilot Part) | Nintedanib 50mg was given as a single dose (Treatment A). Following a wash out period of at least 14 days, ketoconazole 400mg was given once daily for three days and nintedanib 50 mg was given as a single dose 1 hour (h) after the ketoconazole administration with ketoconazole under steady-state conditions (Treatment B) |
| FG001 | Nintedanib+Ketoconazole (Pilot Part)/ Nintedanib (Pilot Part) | Ketoconazole 400mg was given once daily for three days and nintedanib 50 mg was given as a single dose 1 hour (h) after the ketoconazole administration with ketoconazole under steady-state conditions (Treatment B). Following a wash out period of at least 14 days, nintedanib 50mg was given as a single dose (Treatment A). |
| FG002 | Nintedanib (Main Part)/ Nintedanib+Ketoconazole (Main Part) | Based on the results from the Pilot part, nintedanib 50mg was given as a single dose (Treatment C). Following a wash out period of at least 14 days, ketoconazole 400mg was given once daily for 3 days followed by administration of nintedanib 50mg as a single dose 1h after administration of ketoconazole, based on the results from the Pilot part. Nintedanib administration was done under steady state ketoconazole (Treatment D) |
| FG003 | Nintedanib+Ketoconazole (Main Part)/ Nintedanib (Main Part) | Ketoconazole 400mg was given once daily for 3 days followed by administration of nintedanib 50mg as a single dose 1h after administration of ketoconazole, based on the results from the Pilot part. Nintedanib administration was done under steady state ketoconazole (Treatment D). Following a wash out period of at least 14 days, nintedanib 50mg was given as a single dose, based on the results from the Pilot part (Treatment C). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
The treated set (TS) includes all subjects who were dispensed study medication and were documented to have taken at least one dose of study medication (nintedanib or ketoconazole).
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| ID | Title | Description |
|---|---|---|
| BG000 | Overall Study | This was a randomised, open-label trial in healthy male subjects with a 2-way cross-over Pilot part, followed by a 2-way cross-over Main part. Subjects participated either in the Pilot part with 2 treatments (A and B) given in 1 of the 2 treatment sequences (A_B and B_A) or in the Main part with also 2 treatments (C and D) given in 1 of the 2 treatment sequences (C_D and D_C). Nintedanib administrations of the 2 respective treatments (A and B or C and D) were to be separated by a wash-out period of at least 14 days. The Pilot part was separated from the Main part by at least 3 weeks to allow for interim analysis |
| 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 | Area Under the Curve From 0 Extrapolated to Infinity (AUC0-∞) | AUC0-∞ represents the Area under the concentration-time curve of nintedanib in plasma over the time interval from 0 extrapolated to infinity For this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities | The treated set (TS) includes all subjects who were dispensed study medication and were documented to have taken at least one dose of study medication (nintedanib or ketoconazole). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 1 hour (h) before drug administration and 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h and 72h after the drug administration |
|
From the first trial drug administration until 18 days after the last trial drug administration, up to 32 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 | Ketoconazole | In both parts (Pilot and Main) of the study 400 mg ketoconazole were given once daily for 3 days starting on Day -2 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MEDDRA 15.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim Pharmaceuticals | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| ID | Term |
|---|---|
| C530716 | nintedanib |
| D007654 | Ketoconazole |
| ID | Term |
|---|---|
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Nintedanib |
| Drug |
low dose oral administration |
|
| Ketoconazole | Drug | oral administration |
|
| Nintedanib | Drug | low dose oral administration |
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| Nintedanib | Drug | low or medium dose depending on pilot part |
|
| Ketoconazole | Drug | oral administration |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Nintedanib + Ketoconazole | In both parts (Pilot and Main) of the study 400 mg ketoconazole were given once daily for 3 days starting on Day -2 and 50 mg nintedanib were given as a single dose 1 h after the ketoconazole administration on Day 1, with ketoconazole under steady-state conditions. In the Main part, alternatively, a single dose of 100mg could have been given 1 h after the ketoconazole administration or 4 h before the ketoconazole administration on Day 1. The chosen dosing scheme depended on the increase in nintedanib exposure due to ketoconazole co-administration observed in the Pilot part. |
|
|
|
| Primary | Maximum Measured Concentration (Cmax) | Cmax represents the maximum concentration of nintedanib in plasma For this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities | TS | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 1 hour (h) before drug administration and 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h and 72h after the drug administration |
|
|
|
|
| Secondary | Area Under the Curve From 0 to the Last Quantifiable Concentration (AUC0-tz) | AUC0-tz represents the area under the plasma concentration-time curve of nintedanib from time 0 to the last quantifiable nintedanib plasma concentration. For this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities | TS | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 1 hour (h) before drug administration and 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h and 72h after the drug administration |
|
|
|
|
| 0 |
| 34 |
| 2 |
| 34 |
| EG001 | Nintedanib | In both parts (Pilot and Main) 50 mg of nintedanib were given as a single dose on Day 1. In the Main part, alternatively, a single dose of 100mg could have been given. The chosen dosing scheme depended on the increase in nintedanib exposure due to ketoconazole co-administration observed in the Pilot part. | 0 | 31 | 6 | 31 |
| EG002 | Nintedanib + Ketoconazole | In both parts (Pilot and Main) of the study 400 mg ketoconazole were given once daily for 3 days starting on Day -2 and 50 mg nintedanib were given as a single dose 1 h after the ketoconazole administration on Day 1, with ketoconazole under steady-state conditions. In the Main part, alternatively, a single dose of 100mg could have been given 1 h after the ketoconazole administration or 4 h before the ketoconazole administration on Day 1. The chosen dosing scheme depended on the increase in nintedanib exposure due to ketoconazole co-administration observed in the Pilot part. | 0 | 29 | 6 | 29 |
| Headache | Nervous system disorders | MEDDRA 15.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MEDDRA 15.1 | Systematic Assessment |
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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