Carcinoma, Non-Small-Cell LungPhase 1NCT02751385

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

A Phase 1 study testing Microgynon and Nintedanib in people with Carcinoma, Non-Small-Cell Lung, run by Boehringer Ingelheim at 1 site in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

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

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Carcinoma, Non-Small-Cell Lung
What is being tested?: Microgynon and Nintedanib
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 2 participants
Where: 1 siteGermany
Study dates: 20 May 2016to 28 Nov 2017
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 11Show fewer

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

Trial locations and contacts

1 site in 1 country.

Germany1 site

Klinikum Chemnitz gGmbH
Chemnitz, 09116

Other trials in Germany

About this study

Official title: 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

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

Read the detailed description

Purpose:

Conditions: Carcinoma, Non-Small-Cell Lung
Being tested: Microgynon, Nintedanib
Medical subject headings: Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MicrogynonDrug
NintedanibDrug

Study groups in NCT02751385
Study group	Role	What they receive
All Patients	Experimental	Microgynon alone in Period 1 then with Nintedanib in Period 2 Receives: Drug: Microgynon; Drug: Nintedanib

What is being measured

The primary outcome is the main question the study is designed to answer.

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®.
Measured: 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®.
Measured: 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).
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®.
Measured: Please refer to description section for the details about the actual sampling time points

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 May 201628 Nov 2017

First posted26 Apr 2016 (estimated)
Study start20 May 2016
Primary completion28 Nov 2017
Study completion28 Nov 2017

Why it stopped: Terminated- Study halted due to low recruitment.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 2 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02751385
Sponsor's protocol ID: 1199.238
Other IDs: 2015-005664-41, 2015
Status last verified: Nov 2018
First submitted: 22 Apr 2016
Last updated: 14 Mar 2019
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 14 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT02751385
Acronym / sponsor ID: 1199.238
Conditions: Carcinoma, Non-Small-Cell Lung
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Terminated- Study halted due to low recruitment.
Enrolment: 2 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 20 May 2016 (actual)
Primary completion: 28 Nov 2017 (actual)
Study completion: 28 Nov 2017 (actual)
First posted: 26 Apr 2016 (estimated)
Results: Posted 14 Mar 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Purpose:

Study design

Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
All Patients	Experimental	Drug: Microgynon, Drug: NintedanibMicrogynon alone in Period 1 then with Nintedanib in Period 2

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Microgynon	Drug	All Patients
Nintedanib	Drug	All Patients

Primary outcome

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)
Time frame: Please refer to description section for the details about the actual sampling time points
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®.
Maximum Measured Concentration (Cmax) of Ethinylestradiol and Levonorgestrel
Time frame: Please refer to description section for the details about the actual sampling time points
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®.

1 secondary outcome

Area Under the Concentration-time Curve of the Ethinylestradiol and Levonorgestrel in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity).
Time frame: Please refer to description section for the details about the actual sampling time points

Results and safety

Results posted to the registry on 14 Mar 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Microgynon®	2	2
Microgynon® With Nintedanib	0	0

Primary outcome: 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)

Time frame: Please refer to description section for the details about the actual sampling time points. Geometric mean (Geometric Coefficient of Variation). Unit: picogram*hour/mililiter

Measure	Microgynon® n = 2	Microgynon® With Nintedanib n = 2
Ethinylestradiol	410 (6.61)	348 (NA)
Levonorgestrel	41500 (11.0)	43600 (NA)

Population analysed: Pharmacokinetic Set (PKS): This analysis set includes all patients in the Treated Set (TS) who contributes only one PK parameter value for one period to the statistical assessment.

Primary outcome: Maximum Measured Concentration (Cmax) of Ethinylestradiol and Levonorgestrel

Time frame: Please refer to description section for the details about the actual sampling time points. Geometric mean (Geometric Coefficient of Variation). Unit: picogram/milliliter[pg/mL]

Measure	Microgynon® n = 2	Microgynon® With Nintedanib n = 2
Ethinylestradiol	32.6 (3.04)	36.9 (NA)
Levonorgestrel	2680 (23.2)	1630 (NA)

Population analysed: Pharmacokinetic Set (PKS): This analysis set includes all patients in the TS who contributes only one PK parameter value for one period to the statistical assessment.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: From first drug administration until 3 days after the last drug administration. Up to 13 days for Microgynon. From first drug administration until 30 days after the last drug administration. Up to 34 days for nintedanib.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Microgynon®	0 of 2 (0%)	1 of 2 (50%)	0 of 2
Loading Nintedanib	0 of 2 (0%)	1 of 2 (50%)	0 of 2
Nintedanib+Microgynon®	0 of 2 (0%)	1 of 2 (50%)	0 of 2
Nintedanib	0 of 2 (0%)	0 of 2 (0%)	0 of 2

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Boehringer Ingelheim study chair

Boehringer Ingelheim

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Microgynon and Nintedanib in people with Carcinoma, Non-Small-Cell Lung, run by Boehringer Ingelheim at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: Please refer to description section for the details about the actual sampling time points). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02751385.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2019; AzTrials last refreshed its copy on 8 Nov 2026.