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

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)

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.

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