PK PD of EST73502 in HV and patients with chronic osteoarthritis pain
Research type
Research Study
Full title
An exploratory, randomised, double-blind, placebo and active therapy-controlled, Phase I study, to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and food-effect of single and multiple ascending oral doses of EST73502 in healthy adults and patients with chronic, moderate to severe osteoarthritis pain.
IRAS ID
248503
Contact name
Ulrike Lorch
Contact email
Sponsor organisation
ESTEVE PHARMACEUTICALS, S.A.
Eudract number
2018-000258-23
Duration of Study in the UK
1 years, 2 months, 21 days
Research summary
We are conducting a first-in-human clinical study of EST75302 in healthy and patient volunteers. EST75302 is being developed by Esteve as a novel analgesic. Opioids (e.g. morphine, oxycodone) are the mainstay of moderate and severe pain management, but produce many adverse events including addiction and tolerance which seriously limit their usage. In animal models EST75302 has shown similar efficacy to the opioids oxycodone and morphine but with an improved safety profile (fewer effects on the digestive system, central nervous system and reduced tolerance of analgesic effects).\n\nThis is a randomised, doubled-blinded, placebo-controlled phase I study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and food effect of single and multiple oral doses of EST73502. The study will be performed in four parts: Part 1; single ascending doses (up to 9 cohorts of 8 healthy adult Caucasian subjects); Part 2; food effect (1 cohort of 8 healthy adult Caucasian subjects); Part 3; multiple ascending doses (5 cohorts of 19 healthy adult Caucasian subjects) and Part 4; multiple doses in patients with chronic moderate to severe osteoarthritis pain (2 cohorts of 10 patients). In Parts 3 and 4 the safety, tolerability, pharmacokinetic and pharmacodynamics of EST75302 will be compared to the marketed opioid oxycodone. \n\nWe will collect blood and urine samples for pharmacokinetic measurements. We will assess safety parameters including physical examination, vital sign measurements, opioid withdrawal scales, laboratory evaluations, electrocardiogram (ECG) and monitoring of adverse events (AEs). Pharmacodynamic assessments will include pupil size monitoring, bowel function monitoring and bowel transit time, cognitive tests and drug-liking/performance questionnaires. Blood samples for an optional pharmacogenomic assessment will also be collected.\n\nDose escalation to the following scheduled dose or progression to a consecutive part of the study will only occur after satisfactory review of all relevant safety, tolerability and pharmacokinetic data by the Safety Review Committee.\n
REC name
South Central - Berkshire B Research Ethics Committee
REC reference
18/SC/0302
Date of REC Opinion
19 Sep 2018
REC opinion
Further Information Favourable Opinion