Safety and tolerability of BAY63-2521 in Cystic Fibrosis patients

Phase 1

• Conditions: Cystic Fibrosis; MedDRA version: 19.1Level: 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-GB
• Lead Sponsor: Bayer AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-05-16
• Last Update Posted: 11 June 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 63

Inclusion Criteria

1. Signed informed consent available before any study specific tests or procedures are performed
2. Patients must be at least 18 years of age at time of inclusion (i.e. upon signature of informed consent)
3. Patient diagnosed with Cystic Fibrosis according to standard criteria (i.e. either elevated sweat chloride content above 60 mmol/ L and/ or genetic testing)
4. Patient is homozygous for the deltaF508 mutation
5. Patient has a mild-to-moderate stage of lung disease as determined by FEV1 (FEV1 between 40 and 100% predicted)
6. 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
7. Ability and willingness to understand and follow study procedures for the entire study
8. 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
9. Body mass index (BMI): = 16 kg/ m²
Inclusion criterion valid for study part 1 only: 10. 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 criterion valid for study part 2 only: 11. Women of childbearing potential must agree to use adequate contraception when sexually active. 'Adequate contraception' is defined as one highly effective form on contraception (intrauterine devices [IUD], contraceptive implants or tubal sterilisation) 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.
Inclusion criterion valid for study part 2 only: 12. 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
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 61
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion Criteria

1. Patients with Cystic Fibrosis with any background other than homozygous delta F508 mutation
2. Exclusion criterion 2 only valid for study part 1: Patients receiving treatment with Lumacaftor and/or Ivacaftor
3. 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
4. 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
5. A positive sputum culture for Burkholderia cenocepacia, Burkholderia dolosa and/ or Mycobacterium absessus either currently or within the previous year.
6. Active allergic broncho-pulmonary aspergillosis
7. Current pulmonary exacerbation
8. Known history of solid organ transplantation
9. Known history of any form of pulmonary hypertension
10. Known or suspected malignant tumors or a history of malignant tumors
11. 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)
12. Patients with severe hepatic impairment (Child Pugh C) should be excluded
13. Recent evidence (within 12 months prior to inclusion) of distal intestinal obstruction syndrome
14. Patients with creatinine clearance <15 mL/ min or on dialysis need to be excluded.
15. Known history of cardiovascular disease unless stable and without therapy changes in the previous 3 months
16. Known history of clinically relevant arterial hypotension or clinically relevant orthostatic reactions (e.g. as indicated by syncopes, dizziness)
17. Venous/ arterial thromboembolic diseases (particularly deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction)
18. Known current thyroid disorders which require treatment (patients with an euthyroid struma who do not need any treatment can participate)
19. Known hypersensitivity to the study medication (active substances or excipients of the preparations)
20. Documented severe or clinically significant allergic reactions including anaphylaxis or hives
21. Intolerance to lactose requiring strictly lactose-free diet and restriction to lactose-free oral medicines (hereditary galactose intolerance, galactose-glucose malabsorption, lactase deficiency)
22. Recent history (i.e. in the last 12 months prior to screening) of severe hypoglycemic events in patients with severe Cystic Fibrosis diabetes
23. 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
24. Smoking (former smokers who have stopped smoking at least 3 months prior to the first screening visit may be included)
25. Suspicion of drug or alcohol abuse or recent (i.e. within 2 years) history of drug, medicine or alcohol abuse
26. Donation of blood or plasmapheresis after or within 4 weeks of signing the informed consent form
27. 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 (e.g. ketoconazole, itraconazole) or

Study & Design

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