Back to resultsA Study to Test Whether Nintedanib Influences the Components of Birth-control Pills in Women With Systemic Sclerosis Associated Interstitial Lung Disease (SSc-ILD)
Primary Purpose
Scleroderma, Systemic
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Microgynon
Nintedanib
Sponsored by
About this trial
This is an interventional treatment trial for Scleroderma, Systemic
Eligibility Criteria
Inclusion Criteria:
- Age >= 18 years
- A woman of non-child bearing potential, i.e. being postmenopausal1 or permanently sterilised (e.g. hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or a woman of childbearing potential correctly and consistently using a highly effective method of non-hormonal birth control (i.e. IUD or bilateral tubal ligation) together with barrier methods at least 30 days prior to first administration of Microgynon® (Visit 2), during the trial and for 3 months after last intake of nintedanib.
- 2013 American College of Rheumatology (ACR) / European League against Rheumatism (EULAR) classification criteria for Systemic Sclerosis associated Interstitial Lung Disease (SSc) fulfilled
- SSc related Interstitial Lung Disease confirmed by High Resolution Computer Tomography (HRCT); Extent of fibrotic disease in the lung >= 10%
- Forced Vital Capacity (FVC) >= 40% of predicted normal
- Carbon Monoxide Diffusion Capacity (DLCO) 30% to 89% of predicted normal
- Further inclusion criteria apply
Exclusion criteria:
- Aspartate Transaminase (AST), Alanine Transaminase (ALT) >1.5 x Upper Level of Normal (ULN).
- Bilirubin >1.5 x ULN
- Creatinine clearance <30 mL/min
- Clinically relevant anaemia at investigators discretion
- Airway obstruction (pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity (FVC) <0.7)
- Other clinically significant pulmonary abnormalities
- Significant Pulmonary Hypertension (PH)
- Cardiovascular diseases
- More than 3 digital fingertip ulcers or a history of severe digital necrosis requiring hospitalization or severe other ulcers
- Bleeding risk (such as predisposition to bleeding, fibrinolysis, full-dose anticoagulation, high dose antiplatelet therapy, history of hemorrhagic central nervous system (CNS) event within last year
- International normalised ratio (INR) >2, prolongation of prothrombin time (PT) and partial thromboplastin time (PTT) by >1.5 x ULN)
- History of thrombo-embolic event within last year
- Previous or planned hematopoietic stem cell transplantation
- Clinical signs of malabsorption or needing parenteral nutrition
- Patients with underlying chronic liver disease (Child Pugh A, B, C hepatic impairment)
- Previous treatment with nintedanib or pirfenidone
- Further exclusion criteria apply
Sites / Locations
- UNIV UZ Gent
- HOP Avicenne
- HOP Bichat
- Universitätsklinikum Erlangen
- Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg
- Radboud Universitair Medisch Centrum
- Hospital Garcia de Orta, EPE
- Hospital Fernando Fonseca, EPE
- Hospital Santa Creu i Sant Pau
- Hospital Vall d'Hebron
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
All subjects
Arm Description
Outcomes
Primary Outcome Measures
Area Under the Concentration-time Curve of Ethinylestradiol in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of ethinylestradiol in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz).
For Microgynon (ethinylestradiol + levonorgestrel) alone (Reference treatment, R) and Microgynon (ethinylestradiol + levonorgestrel) + nintedanib (Test treatment, T) plasma concentrations of ethinylestradiol were measured 35 minutes (min) before and at 30 min, 1 hour (h), 1h 30 min, 2h, 3h, 4h, 6h, 8h, 11h 55 min, 23h 55 min, 47h 55 min after Microgynon administration alone or in combination with nintedanib.
Area Under the Concentration-time Curve of Levonorgestrel in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of levonorgestrel in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz).
For Microgynon (ethinylestradiol + levonorgestrel) alone (Reference treatment, R) and Microgynon (ethinylestradiol + levonorgestrel) + nintedanib (Test treatment, T) plasma concentrations of levonorgestrel were measured 35 minutes (min) before and at 30 min, 1 hour (h), 1h 30 min, 2h, 3h, 4h, 6h, 8h, 11h 55 min, 23h 55 min, 47h 55 min after Microgynon administration alone or in combination with nintedanib.
Maximum Measured Concentration of Ethinylestradiol in Plasma (Cmax)
Maximum measured concentration of ethinylestradiol in plasma (Cmax). For Microgynon (ethinylestradiol + levonorgestrel) alone (Reference treatment, R) and Microgynon (ethinylestradiol + levonorgestrel) + nintedanib (Test treatment, T) plasma concentrations of ethinylestradiol were measured 35 minutes (min) before and at 30 min, 1 hour (h), 1h 30 min, 2h, 3h, 4h, 6h, 8h, 11h 55 min, 23h 55 min, 47h 55 min after Microgynon administration alone or in combination with nintedanib.
Maximum Measured Concentration of Levonorgestrel in Plasma (Cmax)
Maximum measured concentration of levonorgestrel in plasma (Cmax). For Microgynon (ethinylestradiol + levonorgestrel) alone (Reference treatment, R) and Microgynon (ethinylestradiol + levonorgestrel) + nintedanib (Test treatment, T) plasma concentrations of levonorgestrel were measured 35 minutes (min) before and at 30 min, 1 hour (h), 1h 30 min, 2h, 3h, 4h, 6h, 8h, 11h 55 min, 23h 55 min, 47h 55 min after Microgynon administration alone or in combination with nintedanib.
Secondary Outcome Measures
Area Under the Concentration-time Curve of Ethinylestradiol in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Area under the concentration-time curve of ethinylestradiol in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).
For Microgynon (ethinylestradiol + levonorgestrel) alone (Reference treatment, R) and Microgynon (ethinylestradiol + levonorgestrel) + nintedanib (Test treatment, T) plasma concentrations of ethinylestradiol were measured 35 minutes (min) before and at 30 min, 1 hour (h), 1h 30 min, 2h, 3h, 4h, 6h, 8h, 11h 55 min, 23h 55 min, 47h 55 min after Microgynon administration alone or in combination with nintedanib.
Area Under the Concentration-time Curve of Levonorgestrel in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Area under the concentration-time curve of levonorgestrel in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).
For Microgynon (ethinylestradiol + levonorgestrel) alone (Reference treatment, R) and Microgynon (ethinylestradiol + levonorgestrel) + nintedanib (Test treatment, T) plasma concentrations of levonorgestrel were measured 35 minutes (min) before and at 30 min, 1 hour (h), 1h 30 min, 2h, 3h, 4h, 6h, 8h, 11h 55 min, 23h 55 min, 47h 55 min after Microgynon administration alone or in combination with nintedanib.
Full Information
NCT ID
NCT03675581
First Posted
September 17, 2018
Last Updated
November 5, 2020
Sponsor
Boehringer Ingelheim
1. Study Identification
Unique Protocol Identification Number
NCT03675581
Brief Title
A Study to Test Whether Nintedanib Influences the Components of Birth-control Pills in Women With Systemic Sclerosis Associated Interstitial Lung Disease (SSc-ILD)
Official Title
A Phase I Trial to Investigate the Effect of Nintedanib on the Pharmacokinetics of a Combination of Ethinylestradiol and Levonorgestrel in Female Patients With Systemic Sclerosis Associated Interstitial Lung Disease (SSc-ILD)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
November 8, 2018 (Actual)
Primary Completion Date
October 9, 2019 (Actual)
Study Completion Date
October 10, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The main objective is to assess the potential influence of continuous intake of nintedanib on the systemic exposure of ethinylestradiol and levonorgestrel when administered in combination.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Scleroderma, Systemic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
17 (Actual)
8. Arms, Groups, and Interventions
Arm Title
All subjects
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Microgynon
Intervention Description
fixed sequence trial
Intervention Type
Drug
Intervention Name(s)
Nintedanib
Intervention Description
fixed sequence trial
Primary Outcome Measure Information:
Title
Area Under the Concentration-time Curve of Ethinylestradiol in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Description
Area under the concentration-time curve of ethinylestradiol in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz).
For Microgynon (ethinylestradiol + levonorgestrel) alone (Reference treatment, R) and Microgynon (ethinylestradiol + levonorgestrel) + nintedanib (Test treatment, T) plasma concentrations of ethinylestradiol were measured 35 minutes (min) before and at 30 min, 1 hour (h), 1h 30 min, 2h, 3h, 4h, 6h, 8h, 11h 55 min, 23h 55 min, 47h 55 min after Microgynon administration alone or in combination with nintedanib.
Time Frame
35 minutes (min) before and at 30 min, 1 hour (h), 1h 30 min, 2h, 3h, 4h, 6h, 8h, 11h 55 min, 23h 55 min, 47h 55 min after microgynon administration alone or in combination with nintedanib.
Title
Area Under the Concentration-time Curve of Levonorgestrel in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Description
Area under the concentration-time curve of levonorgestrel in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz).
For Microgynon (ethinylestradiol + levonorgestrel) alone (Reference treatment, R) and Microgynon (ethinylestradiol + levonorgestrel) + nintedanib (Test treatment, T) plasma concentrations of levonorgestrel were measured 35 minutes (min) before and at 30 min, 1 hour (h), 1h 30 min, 2h, 3h, 4h, 6h, 8h, 11h 55 min, 23h 55 min, 47h 55 min after Microgynon administration alone or in combination with nintedanib.
Time Frame
35 minutes (min) before and at 30 min, 1 hour (h), 1h 30 min, 2h, 3h, 4h, 6h, 8h, 11h 55 min, 23h 55 min, 47h 55 min after microgynon administration alone or in combination with nintedanib.
Title
Maximum Measured Concentration of Ethinylestradiol in Plasma (Cmax)
Description
Maximum measured concentration of ethinylestradiol in plasma (Cmax). For Microgynon (ethinylestradiol + levonorgestrel) alone (Reference treatment, R) and Microgynon (ethinylestradiol + levonorgestrel) + nintedanib (Test treatment, T) plasma concentrations of ethinylestradiol were measured 35 minutes (min) before and at 30 min, 1 hour (h), 1h 30 min, 2h, 3h, 4h, 6h, 8h, 11h 55 min, 23h 55 min, 47h 55 min after Microgynon administration alone or in combination with nintedanib.
Time Frame
35 minutes (min) before and at 30 min, 1 hour (h), 1h 30 min, 2h, 3h, 4h, 6h, 8h, 11h 55 min, 23h 55 min, 47h 55 min after microgynon administration alone or in combination with nintedanib.
Title
Maximum Measured Concentration of Levonorgestrel in Plasma (Cmax)
Description
Maximum measured concentration of levonorgestrel in plasma (Cmax). For Microgynon (ethinylestradiol + levonorgestrel) alone (Reference treatment, R) and Microgynon (ethinylestradiol + levonorgestrel) + nintedanib (Test treatment, T) plasma concentrations of levonorgestrel were measured 35 minutes (min) before and at 30 min, 1 hour (h), 1h 30 min, 2h, 3h, 4h, 6h, 8h, 11h 55 min, 23h 55 min, 47h 55 min after Microgynon administration alone or in combination with nintedanib.
Time Frame
35 minutes (min) before and at 30 min, 1 hour (h), 1h 30 min, 2h, 3h, 4h, 6h, 8h, 11h 55 min, 23h 55 min, 47h 55 min after microgynon administration alone or in combination with nintedanib.
Secondary Outcome Measure Information:
Title
Area Under the Concentration-time Curve of Ethinylestradiol in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Description
Area under the concentration-time curve of ethinylestradiol in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).
For Microgynon (ethinylestradiol + levonorgestrel) alone (Reference treatment, R) and Microgynon (ethinylestradiol + levonorgestrel) + nintedanib (Test treatment, T) plasma concentrations of ethinylestradiol were measured 35 minutes (min) before and at 30 min, 1 hour (h), 1h 30 min, 2h, 3h, 4h, 6h, 8h, 11h 55 min, 23h 55 min, 47h 55 min after Microgynon administration alone or in combination with nintedanib.
Time Frame
35 minutes (min) before and at 30 min, 1 hour (h), 1h 30 min, 2h, 3h, 4h, 6h, 8h, 11h 55 min, 23h 55 min, 47h 55 min after microgynon administration alone or in combination with nintedanib.
Title
Area Under the Concentration-time Curve of Levonorgestrel in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Description
Area under the concentration-time curve of levonorgestrel in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).
For Microgynon (ethinylestradiol + levonorgestrel) alone (Reference treatment, R) and Microgynon (ethinylestradiol + levonorgestrel) + nintedanib (Test treatment, T) plasma concentrations of levonorgestrel were measured 35 minutes (min) before and at 30 min, 1 hour (h), 1h 30 min, 2h, 3h, 4h, 6h, 8h, 11h 55 min, 23h 55 min, 47h 55 min after Microgynon administration alone or in combination with nintedanib.
Time Frame
35 minutes (min) before and at 30 min, 1 hour (h), 1h 30 min, 2h, 3h, 4h, 6h, 8h, 11h 55 min, 23h 55 min, 47h 55 min after microgynon administration alone or in combination with nintedanib.
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age >= 18 years
A woman of non-child bearing potential, i.e. being postmenopausal1 or permanently sterilised (e.g. hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or a woman of childbearing potential correctly and consistently using a highly effective method of non-hormonal birth control (i.e. IUD or bilateral tubal ligation) together with barrier methods at least 30 days prior to first administration of Microgynon® (Visit 2), during the trial and for 3 months after last intake of nintedanib.
2013 American College of Rheumatology (ACR) / European League against Rheumatism (EULAR) classification criteria for Systemic Sclerosis associated Interstitial Lung Disease (SSc) fulfilled
SSc related Interstitial Lung Disease confirmed by High Resolution Computer Tomography (HRCT); Extent of fibrotic disease in the lung >= 10%
Forced Vital Capacity (FVC) >= 40% of predicted normal
Carbon Monoxide Diffusion Capacity (DLCO) 30% to 89% of predicted normal
Further inclusion criteria apply
Exclusion criteria:
Aspartate Transaminase (AST), Alanine Transaminase (ALT) >1.5 x Upper Level of Normal (ULN).
Bilirubin >1.5 x ULN
Creatinine clearance <30 mL/min
Clinically relevant anaemia at investigators discretion
Airway obstruction (pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity (FVC) <0.7)
Other clinically significant pulmonary abnormalities
Significant Pulmonary Hypertension (PH)
Cardiovascular diseases
More than 3 digital fingertip ulcers or a history of severe digital necrosis requiring hospitalization or severe other ulcers
Bleeding risk (such as predisposition to bleeding, fibrinolysis, full-dose anticoagulation, high dose antiplatelet therapy, history of hemorrhagic central nervous system (CNS) event within last year
International normalised ratio (INR) >2, prolongation of prothrombin time (PT) and partial thromboplastin time (PTT) by >1.5 x ULN)
History of thrombo-embolic event within last year
Previous or planned hematopoietic stem cell transplantation
Clinical signs of malabsorption or needing parenteral nutrition
Patients with underlying chronic liver disease (Child Pugh A, B, C hepatic impairment)
Previous treatment with nintedanib or pirfenidone
Further exclusion criteria apply
Facility Information:
Facility Name
UNIV UZ Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
HOP Avicenne
City
Bobigny
ZIP/Postal Code
93009
Country
France
Facility Name
HOP Bichat
City
Paris
ZIP/Postal Code
75018
Country
France
Facility Name
Universitätsklinikum Erlangen
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
69126
Country
Germany
Facility Name
Radboud Universitair Medisch Centrum
City
Nijmegen
ZIP/Postal Code
6525 GL
Country
Netherlands
Facility Name
Hospital Garcia de Orta, EPE
City
Almada
ZIP/Postal Code
2801-951
Country
Portugal
Facility Name
Hospital Fernando Fonseca, EPE
City
Amadora
ZIP/Postal Code
2720-276
Country
Portugal
Facility Name
Hospital Santa Creu i Sant Pau
City
Barcelona
ZIP/Postal Code
08026
Country
Spain
Facility Name
Hospital Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). Requestors can use the following link http:// trials.boehringer-ingelheim.com/ to:
find information in order to request access to clinical study data, for listed studies.
request access to clinical study documents that meet criteria, and upon a signed 'Document Sharing Agreement'.
Citations:
PubMed Identifier
34664183
Citation
Vonk MC, Guillen-Del-Castillo A, Kreuter M, Avis M, Marzin K, Mack SR, Wind S, Gahlemann M. A Drug-Drug Interaction Study to Investigate the Effect of Nintedanib on the Pharmacokinetics of Microgynon (Ethinylestradiol and Levonorgestrel) in Female Patients with Systemic Sclerosis-Associated Interstitial Lung Disease. Eur J Drug Metab Pharmacokinet. 2022 Jan;47(1):81-89. doi: 10.1007/s13318-021-00728-7. Epub 2021 Oct 18.
Results Reference
derived
Links:
URL
https://trials.boehringer-ingelheim.com/
Description
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A Study to Test Whether Nintedanib Influences the Components of Birth-control Pills in Women With Systemic Sclerosis Associated Interstitial Lung Disease (SSc-ILD)
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