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)
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 17
- Locations
- 10
- Primary Endpoint
- Area Under the Concentration-time Curve of Ethinylestradiol in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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
Exclusion Criteria
- Not provided
Arms & Interventions
All subjects
Intervention: Microgynon (Drug)
All subjects
Intervention: Nintedanib (Drug)
Outcomes
Primary Outcomes
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.
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.
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.
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
- 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.)