Multi-center, randomized, double-blind, placebo-controlled phase 2 study to assess the safety, tolerability and early signs of efficacy of tid orally administered BAY63-2521 in adult deltaF508 homozygous Cystic Fibrosis patients
- Conditions
- mucoviscidosis1002766410010613
- Registration Number
- NL-OMON42435
- Lead Sponsor
- Bayer HealthCare AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 5
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 and * 32 kg/ m² (calculated by dividing the patient*s weight by the square of his/ her height [kg/ m2])
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.
1. Patients with Cystic Fibrosis with any background other than homozygous deltaF508
mutation
2. Patients receiving treatment with 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 arterial hypertension;11. Known or suspected malignant tumors or a history of malignant tumors
12. 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)
13. Patients with severe hepatic impairment (Child Pugh C) should be excluded
14. Recent evidence (within 12 months prior to inclusion) of distal intestinal obstruction
syndrome.
15. Patients with creatinine clearance <15 mL/ min or on dialysis need to be excluded.
16. Known history of cardiovascular disease unless stable and without therapy changes in
the previous 3 months
17. Known history of clinically relevant arterial hypotension or clinically relevant
orthostatic reactions (e.g. as indicated by syncopes, dizziness)
18. Venous/ arterial thromboembolic diseases (particularly deep vein thrombosis,
pulmonary embolism, stroke, myocardial infarction)
19. Known current thyroid disorders which require treatment (patients with an euthyroid
struma who do not need any treatment can participate)
20. Known hypersensitivity to the study medication (active substances or excipients of
the preparations)
21. Documented severe or clinically significant allergic reactions including anaphylaxis
or hives
22. Intolerance to lactose requiring strictly lactose-free diet and restriction to lactose-free
oral medicines (hereditary galactose intolerance, galactose-glucose malabsorption,
lactase deficiency)
23. Recent history (i.e. in the last 12 months prior to screening) of severe hypoglycemic
events in patients with severe Cystic Fibrosis diabetes
24. 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
25. Smoking (former smokers who have stopped smoking at least 3 months prior to the
first screening visit may be included)
26. Suspicion of drug or alcohol abuse or recent (i.e. within 2 years) history of drug,
medicine or alcohol abuse
27. Donation of blood or plasmapheresis after or within 4 weeks of signing the informed
consent form
28. 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 m
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To assess the safety and tolerability of oral administration of<br /><br>BAY63-2521versus placebo in homozygous deltaF508 Cystic Fibrosis patients<br /><br>To assess early signs of efficacy of BAY63-2521 versus placebo in homozygous<br /><br>deltaF508 Cystic Fibrosis patients as observed by change from baseline in sweat<br /><br>chloride content</p><br>
- Secondary Outcome Measures
Name Time Method <p>To assess early signs of efficacy of BAY63-2521 versus placebo in homozygous<br /><br>deltaF508 Cystic Fibrosis patients as observed by change from baseline in nasal<br /><br>potential difference (NPD), lung clearance index (LCI) and forced expiratory<br /><br>volume in 1 second (FEV1)<br /><br>To assess the pharmacokinetics (PK) of BAY63-2521 and its main metabolite M1<br /><br>(BAY60 4552) in homozygous deltaF508 Cystic Fibrosis patients<br /><br>Additional objective is to evaluate further biomarkers to investigate the drug<br /><br>(i.e. mode-of-action-related effect and/or safety) and/or the pathomechanism of<br /><br>the disease.</p><br>