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Completed

NCT Number: NCT03675581

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

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.

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Key information

Conditions

Scleroderma, Systemic Connective Tissue Diseases Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1

Primary location

UNIV UZ Gent, Ghent, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Microgynon

Drug

fixed sequence trial

Nintedanib

Drug

fixed sequence trial

Primary outcomes

  1. Area Under the Concentration-time Curve of Ethinylestradiol in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)

    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.

    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.

  2. Area Under the Concentration-time Curve of Levonorgestrel in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)

    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.

    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.

  3. Maximum Measured Concentration of Ethinylestradiol in Plasma (Cmax)

    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.

    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.

  4. Maximum Measured Concentration of Levonorgestrel in Plasma (Cmax)

    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.

    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 outcomes

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

    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.

    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.

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

    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.

    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.

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study 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)

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Sep 18, 2018
Registry last updated
Nov 9, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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