A Phase I, Single Oral Dose Study
Research type
Research Study
Full title
PRC-4016 (Icosabutate) - A Phase I, Single-Blind, Placebo-Controlled, Single Oral Dose, Safety, Tolerability and Pharmacokinetic Study in Healthy Subjects
IRAS ID
168558
Contact name
Ashley Brooks
Contact email
Sponsor organisation
Pronova BioPharma Norge AS
Eudract number
2014-005051-31
Duration of Study in the UK
0 years, 1 months, 26 days
Research summary
The study drug (PRC-4016) has been developed as a potential treatment for dyslipidaemia (high levels of cholesterol/ fat in the blood).
PRC 4016 is a novel, orally administered, highly potent, structurally enhanced fatty acid which contains the drug substance PRB 01022 (Icosabutate).
In animal studies Icosabutate has demonstrated reductions in blood cholesterol, and prevented the development of atherosclerosis (cholesterol deposition in blood vessels), and improved liver steatosis (cholesterol deposition in liver). Clinical studies have demonstrated reductions in total cholesterol, and different types of cholesterols like low-density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, and Triglycerides.
In the first-in-human (FIH) study, 157 participants (healthy male and female subjects and subjects with dyslipidaemia) were enrolled and received single oral doses of up to 600 mg PRB 01022 and multiple oral doses of up to 300 mg twice daily (bid) or 600 mg once daily (od). There were no clinically relevant changes in any of the safety parameters evaluated, including vital signs, ECG, physical examinations and laboratory safety assessments.
Reporting is still ongoing for the two Phase 2 proof-of-concept studies in the US and no final data or reports are available. These studies both tested treatment with Icosabutate 600 mg od for 12 weeks versus placebo in a total of 198 patients (safety population). Based on draft data, Icosabutate appeared safe and well tolerated. Adverse events were well balanced between the groups and no serious AEs were reported in the Icosabutate arm. The most commonly reported AEs were gastrointestinal disorders, infections and infestations, and musculoskeletal and connective tissue disorders. No clinically meaningful changes in safety laboratory parameters, vital signs, or physical examination findings were noted.
This will be a placebo controlled, single ascending oral dose, sequential group study conducted in healthy male and female subjects to determine the supra-therapeutic dose level that will be used in an upcoming thorough QT (TQT) study.
Twenty four subjects will be studied in 3 groups (Groups A to C), each group consisting of 8 subjects.
Each subject will participate in 1 treatment period only, residing at the clinical research unit (CRU) from Day 1 (the day before dosing) to Day 2 (after completion of the 36 hour assessments). Subjects will receive a single oral dose of either PRC-4016 or placebo.
All subjects will return for a post-study visit 5 to 7 days after dosing.
The expected duration of subject participation (from screening to post-study) is approximately 5 weeks.REC name
North West - Greater Manchester Central Research Ethics Committee
REC reference
14/NW/1452
Date of REC Opinion
19 Dec 2014
REC opinion
Further Information Favourable Opinion