early signs of efficacy study with riociguat in adult homozygous delta f508 cystic fibrosis patients

Conditions: Cystic Fibrosis

Summary: assessment of the safety, tolerability and early signs of efficacy of three times a day orally administered bay63-2521 in adult delta f508 homozygous cystic fibrosis patients not on treatment with orkambi

the study consists of two parts. the first part is double-blind, randomized and placebo-controlled. the second part has an open-label study design. in part 1 patients on orkambi or other cftr-modulators are excluded. in part 2 patients on orkambi are allowed to be included under certain conditions.

Eligibility criteria:
inclusion criteria: * signed informed consent available before any study specific tests or procedures are performed * patients must be at least 18 years of age at time of inclusion (i.e. upon signature of informed consent) * patient diagnosed with cystic fibrosis according to standard criteria (i.e. either elevated sweat chloride content above 60 mmol/ l and/ or genetic testing) * patient is homozygous for the deltaf508 mutation * patient has a mild-to-moderate stage of lung disease as determined by fev1 (fev1 between 40 and 100% predicted) * patient has a stable condition of lung disease (no ongoing or recent pulmonary exacerbation and no change in current treatment) within the last 4 weeks prior to screening * ability and willingness to understand and follow study procedures for the entire study * patients do not smoke. patients with a history of smoking can be included, if they have refrained from smoking for the last 3 months. if a patients starts smoking during the study participation, he/ she needs to be excluded and considered to be a drop out * body mass index (bmi): ≥ 16 kg/ m² (calculated by dividing the patient's weight by the square of his/ her height \[kg/ m2\]) inclusion criterion valid for study part 1 only: - women of childbearing potential must agree to use adequate contraception when sexually active. 'adequate contraception' is defined as one highly effective form of contraception (intrauterine devices \[iud\], contraceptive implants or tubal sterilization) or a combination of methods (hormone method with a barrier method ). if a partner's vasectomy is the chosen method of contraception or if a partner has documented azoospermia, a hormone or barrier method must be used in combination. adequate contraception is required from the signing of the informed consent form up until 4 weeks after the last study drug administration inclusion criteria valid for study part 2 only: * women of childbearing potential must agree to use adequate contraception when sexually active. 'adequate contraception' is defined as one highly effective form of contraception (intrauterine devices \[iud\], contraceptive implants or tubal sterilization) or a combination of methods (hormone method with a barrier method). for patients on orkambi hormonal methods (including hormonal oral contraceptives) cannot be accepted in this study. they need to choose non-hormonal methods. if a partner's vasectomy is the chosen method of contraception or if a partner has documented azoospermia, a hormone or barrier method must be used in combination. adequate contraception is required from the signing of the informed consent form up until 4 weeks after the last study drug administration * patients receiving orkambi (lumcaftor + ivacaftor) as part of their standard care need to be on stable orkambi treatment for at least 3 months prior to screening (patients on lumacaftor and/or ivacaftor are excluded in part 1) exclusion criteria: * patients with cystic fibrosis with any background other than homozygous deltaf508 mutation * exclusion criterion only valid for study part 1: patients receiving treatment with lumacaftor and/ or ivacaftor * active state of hemoptysis or pulmonary hemorrhage, including those events managed by bronchial artery embolization. also any history of moderate hemoptysis within the 3 months prior to inclusion * any history of pneumothorax, bronchial artery embolization or massive hemoptysis. massive hemoptysis being defined as acute bleeding \>240 ml in a 24-hour period or recurrent bleeding \>100 ml/ d over several days * a positive sputum culture for burkholderia cenocepacia, burkholderia dolosa, and/ or mycobacterium abscessus either currently or within the previous year * active allergic broncho-pulmonary aspergillosis * current pulmonary exacerbation * known history of solid organ transplantation * known history of any form of pulmonary hypertension * clinically relevant deviations of the screened laboratory parameters from reference ranges outside of expected changes for cystic fibrosis patients, especially a hemoglobin value below 110 g/l or a creatinine clearance based on the cockcroft-gault formula \< 15 ml/ min

Keywords: cystic fibrosis delta f508 safety tolerability sweat chloride pharmacokinetics