Safety Study of Fenretinide in Adult Patients With Cystic Fibrosis

NCT ID: NCT02141958

Last Updated: 2016-07-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2015-02-28

Brief Summary

The purpose of this study is to assess the safety and tolerability of ascending doses of a novel oral formulation of Fenretinide to adult cystic fibrosis (CF) patients, once-daily for 21 days (treatment cycle). This study will include up to three (3) dose levels with minimum 7 day breaks in between treatment cycles. For each dose level, blood samples will be collected for exploratory pharmacokinetic (PK) and pharmacodynamic (PD) evaluation.

Detailed Description

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).

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Fenretinide

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.

Group Type: EXPERIMENTAL

Fenretinide

Intervention Type: DRUG

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

Four (4) patients will be on Placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

A matching placebo will be used to keep the study double-blind.

Interventions

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.

Intervention Type: DRUG

Placebo

A matching placebo will be used to keep the study double-blind.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Signed Informed Consent
• Males or females
• 18 years and older
• Diagnosis: Patients must have a diagnosis of cystic fibrosis (positive sweat chloride test) or confirmation of two genetic mutations, one mutation on each of the two alleles of the Cystic fibrosis transmembrane conductance regulator (CFTR) gene causing Cystic Fibrosis
• Chronic cystic fibrosis lung disease with baseline Forced Exploratory Volume in one second equal or superior to 40% predicted value for age, gender and height
• Clinically stable patients will be enrolled in the study, i.e. stable at least one month after successful treatment of pulmonary exacerbation
• Chronic pulmonary Pseudomonas aeruginosa colonization and/or infection (sustained microbiological evidence from sputum for the past 6 months, prior to enrollment)
• Pancreatic function: Patient must take pancrelipase supplementation if diagnosed with pancreatic insufficiency as prescribed by a physician. Enzyme supplementation should not be modified during the trial
• Female patients should be on an effective contraceptive method during the study.

Exclusion Criteria

• Pregnancy : due to the potential teratogenic effects of retinoids, pregnant women are NOT eligible
• Breastfeeding by study patient is NOT allowed
• Clinically abnormal renal function: Serum Creatinine > 132 micromoles/L
• Clinically abnormal liver function: Total bilirubin >1.5 x Upper Limit of the Normal range (ULN), Alanine Aminotransferase (ALT) and/or Aspartate AminoTransferase (AST) > 3 x ULN and Alkaline Phosphatase (ALP) > 2 x ULN
• Known history of a severe allergy or sensitivity to retinoids
• Presence of a cancerous tumor, active or in remission, treated or not
• Presence of nyctalopia or hemeralopia at enrolment, or any other serious retinal, ophthalmological condition (eg: retinitis pigmentosa, choroidoretinitis and xerophthalmia), including glaucoma
• Presence of serious dermatological conditions at entry, including inflammatory or xerotic pathologies such as psoriasis or ichthyosis
• Prior therapy with Fenretinide. Other retinoids (eg: vitamin A supplements) are allowed, but their dosing regimen should remain constant throughout the study
• Participation in another drug clinical trial within 30 days prior to the enrollment
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
• Patients unable to comply with the study protocol and follow-up schedule for any psychological, familial, sociological or geographical reason.
• Patients with known allergies to excipients in the oral capsule formulation proposed to be used in the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Elias Matouk

OTHER

Sponsor Role: lead

Responsible Party

Elias Matouk

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Elias Matouk, MD

Role: PRINCIPAL_INVESTIGATOR

Montreal Chest Institute

Locations

Montreal Chest Institute

Montreal, Quebec, Canada

Countries

Canada

Other Identifiers

MGU-4HPR-13-01

Identifier Type: -

Identifier Source: org_study_id