Investigation of the Effect of Nintedanib on the Pharmacokinetics of a Combination of Ethinylestradiol and Levonorgestrel in Patients With Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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Investigate the effect of multiple oral doses of nintedanib on the single dose kinetics of a combination of ethinylestradiol and levonorgestrel (Microgynon®)

Detailed Description
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Purpose:

Official Title
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A Phase I Trial to Investigate the Effect of Nintedanib on the Pharmacokinetics of a Combination of Ethinylestradiol and Levonorgestrel in Patients With Non-small Cell Lung Cancer

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: Microgynon
* Drug: Nintedanib


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Female patients 18 years or older at screening Female patient is postmenopausal or surgically sterilised Patient with locally advanced, metastatic or locally recurrent non-small cell lung cancer with histology of adenocarcinoma Nintedanib (Vargatef®) is planned to be prescribed in accordance with the marketing authorisation (SmPC) Signed and dated written informed consent in accordance with Good Clinical Practice (GCP) and local legislation prior to admission to the trial Exclusion criteria: Any contraindication to nintedanib (Vargatef®), ethinylestradiol or levonorgestrel (Microgynon®), as specified in the respective labels Use of hormone containing contraceptives (including vaginal and intrauterine devices and including hormone replacement therapy) within 30 days prior to first administration of Microgynon® Systemic use of drugs known to induce (e.g. rifampicin, St. John's Wort, carbamazepine) or to inhibit (e.g. azole antimycotics, macrolides) CYP3A4 within 7 days prior to first trial drug administration until last pharmacokinetic(PK)-sampling in the trial. Exception: allowed is the intake of corticosteroids as docetaxel (pre)medication History of major thrombotic or clinically relevant major bleeding event in the past 6 months Persistence of clinically relevant therapy related toxicities (i.e. > Common Terminology Criteria for Adverse Events [CTCAE] grade 2) from previous chemotherapy and/or radiotherapy Treatment with other investigational drugs or treatment in another clinical trial within the past four weeks before start of therapy or concomitantly with this trial Gastrointestinal disorders or abnormalities that would interfere with absorption of the trial drugs Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to first treatment within the trial and without complete wound healing Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial Patients unable to comply with the protocol Previous enrolment in this trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All Patients<br>Microgynon alone in Period 1 then with Nintedanib in Period 2 | Drug: Microgynon<br> <br> Drug: Nintedanib<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-time Curve of the the Ethinylestradiol and Levonorgestrel in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Area under the concentration-time curve in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC 0-tz) for ethinylestradiol and levonorgestrel after a single dose of the combination of ethinylestradiol and levonorgestrel. In Period 1, blood samples were collected at pre-dose at 0.35 hour (h) and at 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 48h and 72h after drug administration of Microgynon®. Nintedanib in Period 2 was started at least 7 days before Microgynon® administration. In Period 2, blood samples were collected at pre-dose at 0.35 hour (h) and at 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 11.55h, 23.55h, 47.55h and 71.55h after drug administration of Microgynon®. | Please refer to description section for the details about the actual sampling time points | 
| Maximum Measured Concentration (Cmax) of Ethinylestradiol and Levonorgestrel | Maximum blood concentrations (Cmax) for ethinylestradiol and levonorgestrel after a single dose of the combination of ethinylestradiol and levonorgestrel. In Period 1, blood samples were collected at pre-dose at 0.35 hour (h) and at 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 48h and 72h after drug administration of Microgynon®. Nintedanib in Period 2 was started at least 7 days before Microgynon® administration. In Period 2, blood samples were collected at pre-dose at 0.35 hour (h) and at 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 11.55h, 23.55h, 47.55h and 71.55h after drug administration of Microgynon®. | Please refer to description section for the details about the actual sampling time points | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-time Curve of the Ethinylestradiol and Levonorgestrel in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity). | Area under curve from zero to infinity (AUC0-∞) for ethinylestradiol and for levonorgestrel after intake of a single dose of the combination of ethinylestradiol and levonorgestrel. In Period 1, blood samples were collected at pre-dose at 0.35 hour (h) and at 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 48h and 72h after drug administration of Microgynon®. Nintedanib in Period 2 was started at least 7 days before Microgynon® administration. In Period 2, blood samples were collected at pre-dose at 0.35 hour (h) and at 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 11.55h, 23.55h, 47.55h and 71.55h after drug administration of Microgynon®. | Please refer to description section for the details about the actual sampling time points |