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) (1199-0340)

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Clinical trial
• Scope of the study:
  Other
• If ‘other’, further details on the scope of the study:
  Drug-drug interaction, pharmacokinetic trial
• Data collection methods:
  Primary data collection

Clinical trials

• Clinical trial regulatory scope:
  Pre-authorisation clinical trial
• Clinical trial phase:
  Human pharmacology (Phase I)
• Clinical trial randomisation:
  Non-randomised clinical trial

Study drug and medical condition

• Name of medicine:
  OFEV
• Name of medicine, other:
  Microgynon
• Medical condition to be studied:
  Systemic sclerosis pulmonary

Population studied

• Short description of the study population:
  Female patients aged 18 years or older with SSc-ILD fulfilling the 2013 ACR/EULAR classification criteria for SSc; extent of fibrotic lung disease ≥10% on high resolution computed tomography (HRCT); forced vital capacity (FVC) ≥40% of predicted;carbon monooxide diffusion capacity of the lung (DLCO) 30 TO 89% predicted. Patients had to be permanently sterilised or postmenopausal or using a highly effective non-hormonal method of birth control in combination with a barrier method.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  Systemic Sclerosis associated Interstitial Lung Disease (SSc-ILD) patients
• Estimated number of subjects:
  21

Study design details

• Main study objective:
  To investigate the effect of multiple oral doses of nintedanib on the single dose kinetics of a combination of ethinylestradiol and levonorgestrel (Microgynon®)
• Outcomes:
  AUC0-tz and Cmax for ethinylestradiol and levonorgestrel, AUC0-infinity for ethinylestradiol and levonorgestrel
• Data analysis plan:
  Relative exposure of ethinylestradiol and levonorgestrel will be estimated based on the ratios (test to reference treatment) of the geometric means (gMeans) of the primary and secondary endpoints. Additionally, their 2-sided 90% confidence intervals (CIs) will be provided. The statistical model will be an analysis of variance (ANOVA) on the logarithmic scale, including effects for 'subject' and 'treatment'. CIs will be calculated based on the residual error from ANOVA. Descriptive statistics will be calculated for all endpoints.