A Study to Test Whether Nintedanib Influences the Components of Birth-control Pills in Women With Systemic Sclerosis Associated Interstitial Lung Disease (SSc-ILD)

NCT03675581 | Completed Phase 1 Results

• 2 other identifiers: 1199-03402018-001177-24
• Study Type: interventional
• Target: 17
• Locations: 6 countries
• Sites: 10

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.

Conditions

Scleroderma, Systemic

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  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 Outcomes (2)

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

  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-∞)

  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.

Study Arms (1)

All subjects

EXPERIMENTAL

Drug: Microgynon; Drug: Nintedanib

Interventions

Microgynon DRUG

fixed sequence trial

All subjects

Nintedanib DRUG

fixed sequence trial

All subjects

Eligibility Criteria

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

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (10)

UNIV UZ Gent

Ghent, 9000, Belgium

Location

HOP Avicenne

Bobigny, 93009, France

Location

HOP Bichat

Paris, 75018, France

Location

Universitätsklinikum Erlangen

Erlangen, 91054, Germany

Location

Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg

Heidelberg, 69126, Germany

Location

Radboud Universitair Medisch Centrum

Nijmegen, 6525 GL, Netherlands

Location

Hospital Garcia de Orta, EPE

Almada, 2801-951, Portugal

Location

Hospital Fernando Fonseca, EPE

Amadora, 2720-276, Portugal

Location

Hospital Santa Creu i Sant Pau

Barcelona, 08026, Spain

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Related Publications (1)

• 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.

  PMID: 34664183 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Scleroderma, Systemic

Interventions

ethinyl estradiol, levonorgestrel drug combination; nintedanib

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Results Point of Contact

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

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

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: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2018
• First Posted: September 18, 2018
• Study Start: November 8, 2018
• Primary Completion: October 9, 2019
• Study Completion: October 10, 2019
• Last Updated: November 9, 2020
• Results First Posted: November 9, 2020

Record last verified: 2020-11

Locations

NL (1); ES (2); BE (1); FR (2); DE (2); PT (2)