A Phase II, dose ranging, multicenter, double-blind, placebo controlled study to evaluate safety and efficacy of (R)-roscovitine in subjects with Cystic Fibrosis.
- Conditions
- Cystic Fibrosis treated by 'roscovitine' in subjects homozygous for the F508del-CFTR mutation and chronically infected with Pseudomonas aeruginosa.MedDRA version: 18.0Level: PTClassification code 10011762Term: Cystic fibrosisSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2015-002911-13-FR
- Lead Sponsor
- CHRU de Brest
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 36
Patients eligible for inclusion in this study have to fulfill all of the following criteria:
– Male or female aged over 18 years of age on the date of informed consent
– Diagnosed CF patients. Confirmed diagnosis of CF is defined as (Rosenstein and Cutting, 1998):
o A sweat chloride value > or = 60 mmol/L by quantitative pilocarpine iontophoresis OR 2 CF-causing mutations
o AND chronic sinopulmonary disease OR gastrointestinal/nutritional abnormalities
– Homozygous for the F508del-CFTR mutation, genotype to be confirmed at screening;
– Positive sweat test (sweat chloride > or = 60 mmol/L) at screening;
– Forced expiratory volume at 1 second (FEV1) > or = 40% of normal predicted values for age, sex and height based on the Knudson equation;
– FEV1 at Day 1 must be within 15% of FEV1 at Screening. If FEV1 at Day 1 is not within 15% of FEV1 at Screening, Visit 2 can be repeated within 7 days and rescheduled once;
– Chronic lung Pseudomonas aeruginosa infection according to the definition from the French Consensus Conference as recommended by the Committee for Medicinal Products for Human use (CMPH) of the European Medicines Agency (EMA).Clinically stable CF disease in the opinion of the investigator;
– Able to understand and comply with all protocol requirements, restrictions and instructions and likely to complete the study as planned (as judged by the investigator);
– Provide written informed consent prior to the performance of any study-related procedure;
– Be affiliated to health insurance;
– Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
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 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6
Patients fulfilling any of the following criteria are not eligible for inclusion in this study:
– Acute upper or lower respiratory infection, pulmonary exacerbation or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before V2
– Recent patient reported history of
o non recovered viral upper respiratory tract infection
o solid organ or hematological transplantation
– Undergone major surgery within 1 month prior to screening
– Currently treated allergic broncho-pulmonary aspergillosis (ABPA)
– Diabetic patients whose blood glucose is poorly controlled as evidenced by HbA1C >8%
– Hemoptysis more than 60 mL at any time within 4 weeks prior to first study drug administration (V2)
– History of any other comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject.
– Any other clinically significant conditions (not associated with the study indication) at Screening (V1) which might interfere with the assessment of this study
– Any of the following abnormal laboratory values at screening:
o Hemoglobin <10 g/dL
o Abnormal liver function defined as any 3 or more of the following:
> or = 3 x upper limit of normal (ULN) aspartate aminotransferase (AST)
> or = 3 x ULN alanine aminotransferase (ALT)
> or = 3 x ULN gamma-glutamyl transpeptidase
> or = 3 x ULN alkaline phosphatase
Or > or = 2 x ULN total biliburin
o Serum K+ <3,5 mmol/L
o Abnormal renal function defined as a creatinine clearance <50 mL/min/m2 / glomerular filtration rate < or = 50 mL/min/1,73 m2 (calculated by the Modification of Diet in Renal Disease Study Equation) (Levey et al, 1999, 2006)
– Any clinically significant laboratory abnormalities (not associated with the study indication) at screening that would interfere with the study assessment or pose an undue risk for the subject (as judged by the investigator)
– Patients who have clinically significant impairment in cardiovascular function or are at risk thereof, as evidenced by:
o Congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, clinically significant bradycardia, high grade AV block, history of acute MI less than one year prior to study entry
o A 12- lead ECG at screening demonstrating QTcF>450 or showing clinically significant abnormality including prolonged QT. If the QTcF exceeds 450 msec for the screening ECG, the ECG should be repeated 2 more times during the screening period, and the average of the 3 QTcF values should be used to determine the subject’s eligibility.
o History of syncope or family history of idiopathic sudden death
o Risk factors for Torsades de Pointes such as uncorrected hypokalemia, uncorrected hypomagnesemia, cardiac failure
– Concomitant disease(s) that could prolong the QT interval.
– Patients with a history of alcohol or drug abuse in the past year, including but not limited to tobacco, cannabis, cocaine, and opiates as deemed by investigator
– Patients with a history of noncompliance to medical regimens and patients or caregivers who are considered potentially unreliable
– Use of one (or several) prohibited medications and/or food within 30 days prior to Screening (V1)
– Administration of any investigational drug within 30 days prior to Screening (V1) or 5 half-lives, whichever is longer
– Use of systemic anti-pseudomonal antibiotics within 28 days prior to
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method