A Study to Evaluate the Safety of Fenretinide in Healthy Volunteers

NCT06181760 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: ISLA101-P01-CT001
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial was to learn about a single dose of fenretinide in healthy volunteers, in both a fasted and fed state. The main questions to answer were:

• How well is a single dose of fenretinide tolerated? AND
• How is a single dose of fenretinide metabolized in healthy volunteers? Participants will be asked to:
• Remain confined in a clinical research unit for 5 days after dosing.
• Provide blood samples for intense PK sampling and safety labs.
• Fast for 10 hours prior to administration of study drug (fasted cohorts).
• Consume a high fat meal prior to administration of study drug (fed cohort).
• Return to the clinic for a single follow-up visit for safety assessments. The study will compare active fenretinide to placebo to see if fenretinide is more or less tolerable than placebo.

Conditions

Safety and Tolerability

Outcome Measures

Primary Outcomes (4)

• Number and % of Subjects Experiencing Adverse Events Following a Single Oral Dose of Fenretinide Under Fasted Conditions

  First Intervention (Day 1 to Day 8)

• Number and % of Subjects Experiencing Serious Adverse Events Following a Single Oral Dose of Fenretinide Under Fasted Conditions

  25 total subjects were enrolled in the study.

  First Intervention (Day 1 to Day 8)

• Number and % of Subjects Experiencing Adverse Events Following a Single Oral Dose of Fenretinide Under Fed Conditions

  Subjects in the 600 mg/m\^2 came back to complete the fed cohort, as this was the only group to return based on the recommendations by the Safety Review Committee. Only 4 out of the 6 subjects returned for this cohort (i.e., 3 subjects on ISLA101 and 1 subject on placebo).

  Second Intervention (Day 9 to Day 17)

• Number and % of Subjects Experiencing Serious Adverse Events Following a Single Oral Dose of Fenretinide Under Fed Conditions

  25 total subjects were enrolled in the study. After all fasted cohorts completed (i.e., 300 mg/m\^2, 600 mg/m\^2, 900 mg/m\^2 as well as placebo) data was reviewed by the independent Safety Review Committee. The recommendation was to bring back the 600 mg/m\^2 group to complete the fed cohort and only 4 out of the 6 subjects were available (i.e., 3 subjects on ISLA101 and 1 subject on placebo).

  Second Intervention (Day 9 to 17)

Secondary Outcomes (5)

• Assess the CMax - Observed Maximum Plasma Concentration Following a Single Oral Dose of Fenretinide

  First Intervention (Day 1 to Day 8), washout period, Second Intervention (Day 9-17)

• Assess the TMax - Time to Reach Maximum Concentration Curve Following a Single Oral Dose of Fenretinide in the Fasted and Fed State

  First Intervention (Day 1 to Day 8), washout period, Second Intervention (Day 9-17)

• Assess the AUC-∞ Area Under the Concentration Curve From Zero to Infinite Time Following a Single Oral Dose of Fenretinide in the Fasted and Fed State

  First Intervention (Day 1 to Day 8), washout period, Second Intervention (Day 9-17)

• Assess the AUC(Last) - Area Under the Curve up to the Last Quantifiable Timepoint After a Single Oral Dose of Fenretinide in the Fasted and Fed State

  First Intervention (Day 1 to Day 8), washout period, Second Intervention (Day 9-17)

• Assess the Half Life of a Single Oral Dose of Fenretinide in the Fasted and Fed State

  First Intervention (Day 1 to Day 8), washout period, Second Intervention (Day 9-17)

Study Arms (4)

Fenretinide 300 mg/m^2

ACTIVE COMPARATOR

Single oral dose of fenretinide, 300 mg/m\^2 under fasted conditions (Phase 1)

Drug: Fenretinide

Fenretinide 600 mg/m^2

ACTIVE COMPARATOR

Single oral dose of fenretinide, 600 mg/m\^2 under fasted conditions (Phase 1) Once all groups finish Phase 1, return to complete Phase 2 with a single oral dose of fenretinide, 600 mg/m\^2 under fed conditions per recommendation from the independent Safety Review Committee.

Drug: Fenretinide

Fenretinide 900 mg/m^2

ACTIVE COMPARATOR

Single oral dose of fenretinide, 900 mg/m\^2 under fasted conditions (Phase 1)

Drug: Fenretinide

Placebo

PLACEBO COMPARATOR

Single oral dose of placebo capsules under fasted conditions (Phase 1) Once all groups finish Phase 1, return to complete Phase 2 with a single oral dose of placebo capsules under fed conditions per recommendation from the independent Safety Review Committee.

Drug: Placebo

Interventions

Fenretinide DRUG

Ascending single doses of oral fenretinide

Fenretinide 300 mg/m^2; Fenretinide 600 mg/m^2; Fenretinide 900 mg/m^2

Placebo DRUG

Single oral dose of matching placebo capsules

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male or female volunteers not of childbearing potential, who are 18 years to 65 years of age (inclusive) at the time of signing the informed consent form (ICF).
• Females not of childbearing potential, as defined in the following criteria:
• History of hysterectomy.
• Post-menopausal.
• i. Natural post-menopausal females with at least 12 months from natural spontaneous amenorrhea and a serum follicle-stimulating hormone (FSH) concentration ≥ 40 IU/L.
• ii. Post-surgical females must have undergone bilateral oophorectomy at least 6 weeks prior to study.
• Male subjects with female partners of childbearing potential must agree to practice abstinence or use a combination of 2 of the following acceptable birth control methods during the study and for at least 90 days after dosing:
• Partners have an intrauterine device (IUD) without hormones in place for at least 3 months.
• Barrier method (condom or diaphragm) for at least 14 days prior to screening and 90 days after dosing with study drug.
• Partners using stable hormonal contraceptive for at least 3 months prior to screening and for 90 days after dosing with study drug.
• History of vasectomy at least 3 months prior to signing the ICF.
• Must be able to understand and provide signed informed consent for study participation.
• Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Body mass index (BMI) 18.0 to 32.0 kg/m2 (inclusive), and a body weight ≥ 50 kg.
• Normal renal function, defined as estimated glomerular filtration rate (eGFR) ≥ 70 mL/min/1.73 m2 at screening and Day -1.

You may not qualify if:

• Known or suspected pregnancy (confirmed via a positive serum human chorionic gonadotropin \[hCG\] pregnancy test at screening), planned pregnancy during the study period, nursing, or lactation.
• Women of childbearing potential or men who intend to father a child or donate sperm during the study period and for 3 months after study drug administration.
• Known allergy to fenretinide or any of the components of ISLA101.
• History of severe infectious disease or recurrent infections.
• Aspartate transaminase (AST), alanine aminotransferase (ALT), or total bilirubin above the 1.5 x upper limit of normal (ULN) at screening and Day -1.
• Clinically significant electrocardiogram (ECG) abnormalities or vital sign abnormalities at screening and Day -1, long QT syndrome, or a history of cardiac disease.
• Abnormal diet that may affect absorption, distribution, metabolism, or excretion of drugs, for example, lacking standard nutrients (e.g, cleansing diet 2 weeks before or during the study).
• Positive result for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) at screening.
• History of positive test for tuberculosis (TB) at screening.
• A subject who has donated 1 unit of blood of over 500 mL within 56 days prior to the study drug administration, or donated plasma within 14 days prior to study drug administration.
• Use of systemic antibiotics within 30 days prior to dosing.
• Any use of drugs that inhibit or induce CYP enzymes within 30 days prior to administration of study drug and for the duration of study participation.
• Use of any tobacco products, e-cigarettes, and/or nicotine replacement products in the 3 months preceding screening.
• Any food allergy, intolerance, or restriction that, in the opinion of the Investigator, could contraindicate the subject's participation in this study.
• Recent history of (within the past 12 months), or strong potential for, alcohol or substance abuse. Alcohol abuse will be defined as \> 14 drinks per week (1 drink = 10g of ethanol).

Sponsors & Collaborators

• Island Pharmaceuticals: lead
• Beyond Drug Development: collaborator

Study Sites (1)

Island Site 01

Randwick, New South Wales, 2031, Australia

Location

MeSH Terms

Interventions

Fenretinide

Intervention Hierarchy (Ancestors)

Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors

Results Point of Contact

• Title: David Foster, CEO
• Organization: Island Pharmaceuticals

dfoster@islandpharmaceuticals.com

510-393-6523

Study Officials

• Christopher Argent, MD

  Scientia Clinical Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Identical placebo
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo controlled

Study Record Dates

• First Submitted: October 25, 2023
• First Posted: December 26, 2023
• Study Start: November 22, 2023
• Primary Completion: February 13, 2024
• Study Completion: February 13, 2024
• Last Updated: January 27, 2025
• Results First Posted: January 27, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)