Safety, tolerability, pharmacokinetics and preliminary pharmacodynamics of QBW251 in healthy subjects and cystic fibrosis patients.

• Conditions: cystic fibrosis; MedDRA version: 18.0Level: PTClassification code 10011762Term: Cystic fibrosisSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2011-005085-37-FR
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-06-17
• Last Update Posted: 25 January 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

For Parts 3 and 4
1.Written informed consent must be obtained before any assessment is performed.
2.Male and female patients of 18 to 55 years of age (included) with a confirmed diagnosis of cystic fibrosis as per the Cystic Fibrosis Foundation (CFF) consensus guidelines .
3.A documented CFTR genotype defined as a class III, IV, V, or VI mutation on one allele and on the other allele any other CFTR mutation with the exception of F508del/F508del due to its designation as either a class II or III mutation.
4. Patients must be willing to undergo genetic testing to confirm the CFTR genotype.
5.At screening and baseline, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position after the subject has rested for at least three minutes and again after three minutes in the standing position. Sitting vital signs should be within the following ranges:
•oral body temperature between 35.0-37.5°C
•systolic blood pressure, 90-140 mm Hg
•diastolic blood pressure, 50-90 mm Hg
•pulse rate, 40 - 90 bpm
Patients should be excluded if their standing vital signs (relative to sitting) show findings which, in the opinion of the Investigator, are associated with clinical manifestation of postural hypotension (i.e. absence of any other cause).
6.Patients must have a body mass index (BMI) within the range of 15 -35 kg/m2.
7.FEV1 at Screening must be 50 to 90% predicted (inclusive) for Part 3 and 40 to 100% predicted (inclusive) for Part 4 by NHANES/Hankinson standards.
8.Oxygen saturation (O2) at screening must be = 90 % on room air.
9.Able to perform reliable, reproducible pulmonary function test maneuvers per American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines (Miller et al 2005) at screening.
10.Able to perform reliable, reproducible Lung Clearance Index test maneuvers as evaluated by over reading by EcoMedics at screening.
11.Able to communicate well with the investigator, to understand and comply with the requirements of the study. Subjects should be able to understand and sign the written informed consent.
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 156
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

For Part 3 and 4
1.Use of other investigational drugs at the time of enrollment; or within 5 half-lives or within 30 days of enrollment, or until the expected PD effect has returned to baseline.
2.History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
3.A history of clinically significant ECG abnormalities, or ECG abnormalities at screening
4. History or presence of prolonged QT syndrome.
5.History of malignancy of any organ system (other than localized basal cell carcinoma of the skin) within the past 5 years.
6.Pregnant or nursing (lactating) women.
7.Women of child-bearing potential, unless they are using contraception during the study and until study completion.
8.Sexually active males must use a condom during intercourse while taking drug and for 2 weeks after stopping study medication and should not father a child in this period.
9.Use of any herbal supplements within 4 weeks prior to initial dosing.
10.Smokers
11.Use of prescription drugs prohibited in Section 5.4.9.2.
12.Donation or loss of 400 mL or more of blood within 8 weeks prior to
initial dosing, or longer if required by local regulation.
13.Plasma donation (>400 mL) within 28 days prior to first dosing.
14.Hemoglobin levels below 10.0 g/dl at screening.
15.Clinical instability.
16.Recent and/or recurrent history of autonomic dysfunction.
17.Any surgical or medical condition which might significantly alter the
absorption, distribution, metabolism, or excretion of drugs, or which
may jeopardize the subject in case of participation in the study.
18.History of immunodeficiency diseases, including a positive HIV test result.
19.A positive Hepatitis B surface antigen or Hepatitis C test result.
20.History of drug or alcohol abuse
21.Unwilling to avoid direct sun exposure.
22.Any upper respiratory tract infection.
23.Any changes in concomitant medications for 14 days prior to screening throughout the end of study visit.
24.History of Burkholderia cepacia respiratory tract infection and/or Mycobacterium abbesses and/or other atypical mycobacterial species infection.
25.History of lung transplant.
26.History of clinically significant hemoptysis.
27.Patients with known adrenal dysfunction (+/- adrenal replacement therapy).
28.Patient is currently receiving (or has received within 4 weeks of baseline visit) VX-770/Ivacaftor.
29.Vulnerable subjects

Study & Design

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