Safety and tolerability of BAY63-2521 in Cystic Fibrosis patients

Phase 1

• Conditions: Cystic Fibrosis; MedDRA version: 18.0Level: PTClassification code 10011762Term: Cystic fibrosisSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2013-004595-35-NL
• Lead Sponsor: Bayer HealthCare AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-07-09
• Last Update Posted: 23 October 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 40

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 60 and 90% 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 and = 32 kg/ m²
- 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 or two barrier 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 38
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion Criteria

- Patients with Cystic Fibrosis with any background other than homozygous deltaF508 mutation
- Patients receiving treatment with 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 absessus 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 arterial hypertension
- Nasal conditions that would interfere with conducting NPD. Well controlled seasonal allergic rhinitis is not an exclusion criterion.
- Known or suspected malignant tumors or a history of malignant tumors
- Unstable liver disease as indicated by
a.bilirubin >2 times upper limit normal (ULN) and/ or hepatic transaminases >5 times ULN
b.signs of severe hepatic insufficiency (e.g. impaired albumin synthesis with an albumin < 32g/ L, hepatic encephalopathy > Grade 1a)
- Patients with severe hepatic impairment (Child Pugh C) should be excluded
- Recent evidence (within 12 months prior to inclusion) of distal intestinal obstruction syndrome.
- Patients with creatinine clearance <15 mL/ min or on dialysis need to be excluded.
- Known history of cardiovascular disease unless stable and without therapy changes in the previous 3 months
- Known history of clinically relevant arterial hypotension or clinically relevant orthostatic reactions (e.g. as indicated by syncopes, dizziness)
- Venous/ arterial thromboembolic diseases (particularly deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction)
- Known current thyroid disorders which require treatment (patients with an euthyroid struma who do not need any treatment can participate)
- Known hypersensitivity to the study medication (active substances or excipients of the preparations)
- Documented severe or clinically significant allergic reactions including anaphylaxis or hives
- Intolerance to lactose requiring strictly lactose-free diet and restriction to lactose-free oral medicines (hereditary galactose intolerance, galactose-glucose malabsorption, lactase deficiency)
- Recent history (i.e. in the last 12 months prior to screening) of severe hypoglycemic events in patients with severe Cystic Fibrosis diabetes
- Any medical disorder, condition, or history of such that would impair the patient's ability to participate or complete this study in the opinion of the investigator
- Smoking (former smokers who have stopped smoking at least 3 months prior to the first screening visit may be included)
- Suspicion of drug or alcohol abuse or recent (i.e. within 2 years) history of drug, medicine or alcohol abuse
- Donation of blood or plasmapheresis after or within 4 weeks of signing the informed consent form
- Concomitant use of the following medication: nitrates or nitric oxide donors (such as amyl nitrite) in any form, PDE 5 inhibitors (such as sildenafil, tadalafil, vardenafil), strong multi pathway CYP and p-gp/ BCRP inhibitors such as azole antimycotics

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified