Safety Study of Fenretinide in Adult Patients With Cystic Fibrosis
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|ClinicalTrials.gov Identifier: NCT02141958|
Recruitment Status : Completed
First Posted : May 20, 2014
Last Update Posted : July 12, 2016
|Condition or disease||Intervention/treatment||Phase|
|Cystic Fibrosis||Drug: Fenretinide Drug: Placebo||Phase 1|
Patients with cystic fibrosis have an innate imbalance of essential fatty acids, with increased arachidonic acid (AA) levels, decreased docosahexanoic acid (DHA) levels, and elevated AA/DHA ratio. An increasing amount of evidence suggests that this lipid imbalance is a primary effect in CF, playing a major role in the infection-inflammation vicious cycle that leads to respiratory failure. Fenretinide, a derivative of vitamin A, was shown to correct the AA/DHA imbalance in lungs and blood plasma in specific animal model of CF, resulting in reduced lung inflammation and decrease in the severity of pulmonary infections with Pseudomonas aeruginosa.
This is a single center, randomized, double-blinded, placebo-controlled Phase 1 clinical study to evaluate the safety and tolerability of up to 3 increasing oral doses of Fenretinide compared to placebo, and to evaluate the pharmacokinetics of Fenretinide in adult CF patients chronically infected with Pseudomonas aeruginosa. A single cohort of 16 clinically stable adult patients will be randomized to either Fenretinide or placebo, in a 3:1 randomization scheme (12 active, 4 placebo).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||An Adaptive Phase I Intra-patient Dose Escalation Study of Fenretinide in Adult Cystic Fibrosis Patients|
|Study Start Date :||April 2014|
|Actual Primary Completion Date :||February 2015|
|Actual Study Completion Date :||February 2015|
Fenretinide will be administrated orally once per day for 21 consecutive days, in up to three treatment cycles of ascending doses, with a minimum of 7-day drug-free period between cycles. Twelve (12) patients will be on Fenretinide.
Fenretinide oral capsules of 100mg, each selected dose being administered once daily for 21 days (treatment cycle). Up to three total daily dose levels will be assessed in the study, as follows: 100mg of Fenretinide (one capsule) for the first treatment cycle, 200mg of Fenretinide (two capsules) in the second treatment cycle, and 300mg or 400mg of Fenretinide (3 or 4 capsules) will be selected for the third treatment cycle, based on safety and PK data collected.
Placebo Comparator: Placebo
Four (4) patients will be on Placebo.
A matching placebo will be used to keep the study double-blind.
- Assessment of the safety and tolerability of ascending doses of oral Fenretinide, each dose to be administered to adult cystic fibrosis (CF) patients once-daily (QD) during a 21 days treatment cycle. [ Time Frame: During a 21 days treatment cycle, from time taking first dose (Day 1) through last day of each treatment cycle (Day 21) ]Changes in clinical signs and symptoms of safety data during a 21 days treatment cycle, such safety data assessment including physical examinations, ECGs, vital signs, pulmonary function (spirometry), clinical laboratory results, assessment of ophthalmological condition, and adverse events reported. The safety data will be used to authorize dose escalations. Up to three (3) doses of Fenretinide will be assessed in up to three (3) treatment cycles of 21 days.
- Pharmacokinetic profile of the drug, measuring Cmax, Tmax, T1/2, AUC (area under the curve) and Css (steady state concentration), for each dose level [ Time Frame: Day 1 and 21 of each treatment cycle ]Cmax, Tmax, T 1/2, and Css (steady state concentration) with target plasma levels of Fenretinide 1-2 µM as a pharmacokinetic / pharmacodynamic biological activity
- Pharmacodynamic lipid markers: plasma Arachidonic Acid (AA) and Docosahexaenoic Acid (DHA) [ Time Frame: At baseline and Day 21 of each treatment cycle ]Arachidonic Acid as omega-6 proinflammatory fatty acid and Docosahexaenoic Acid (DHA) as an omega-3 anti-inflammatory fatty acid.
- Pharmacodynamic inflammatory markers: Immunoglobulin G, Interleukin 1β, Interleukin 6, Interleukin 8, Interleukin 10, Macrophage inflammatory protein-1β, Tumor necrosis factors and Vascular endothelial growth factor [ Time Frame: At baseline and Day 21 of each treatment t cycle ]
- Pre-specified exploratory parameter: pulmonary function using the Forced Expiratory Volume in 1 second test [ Time Frame: At baseline and Day 21 of each treatment cycle ]Forced expired volume in 1 second as percent predicted according to age, gender and height
- Pre-specified exploratory parameter: quality of life using the Cystic Fibrosis Quality of life Questionnaire Revised (CFQ-R) [ Time Frame: At baseline and Day 21 of each treatment cycle ]respiratory symptom score, physical domain and health perception domain
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02141958
|Montreal Chest Institute|
|Montreal, Quebec, Canada, H2X 2P4|
|Principal Investigator:||Elias Matouk, MD||Montreal Chest Institute|