Early Signs of Efficacy Study With Riociguat in Adult Homozygous Delta F508 Cystic Fibrosis Patients
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: Riociguat (Adempas, BAY63-2521); Placebo
Intervention description: Participants received 0.5 mg BAY63-2521 three times daily (tid) for 14 days. The dose would be increased to 1 mg BAY63-2521 for an additional 14 days, if this was considered safe and tolerable on the basis of the available data for a given patient.; Participants received matching placebo tid.
Intervention MeSH terms: Riociguat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cystic fibrosis; delta F508; Safety; Tolerability; Sweat Chloride; Pharmacokinetics

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
    

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