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

NCT02751385 | Terminated Phase 1 Results

• 2 other identifiers: 1199.2382015-005664-41
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Area Under the Concentration-time Curve of the Ethinylestradiol and Levonorgestrel in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity).

  Please refer to description section for the details about the actual sampling time points

Study Arms (1)

All Patients

EXPERIMENTAL

Microgynon alone in Period 1 then with Nintedanib in Period 2

Drug: Microgynon; Drug: Nintedanib

Interventions

Microgynon DRUG

All Patients

Nintedanib DRUG

All Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

Klinikum Chemnitz gGmbH

Chemnitz, 09116, Germany

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

ethinyl estradiol, levonorgestrel drug combination; nintedanib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2016
• First Posted: April 26, 2016
• Study Start: May 20, 2016
• Primary Completion: November 28, 2017
• Study Completion: November 28, 2017
• Last Updated: March 14, 2019
• Results First Posted: March 14, 2019

Record last verified: 2018-11

Locations

DE (1)