(resubmission)Safety, tolerability, PK and PD of Ulimorelin (117426)
Research type
Research Study
Full title
A Phase I, Randomised, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Ulimorelin (LP101) after Single and Multiple Intravenous Doses in Healthy Adult Subjects.
IRAS ID
182312
Contact name
Joyce James
Sponsor organisation
Lyric Pharmaceuticals Inc.
Eudract number
2015-001257-32
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
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Duration of Study in the UK
0 years, 4 months, 29 days
Research summary
Most ICU patients receive required nutrition via a feeding tube (enteral feeding). Up to 30% develop impaired gastric emptying such that delivered protein and calories remains in the stomach rather than being absorbed, leading to malnutrition. This condition is known as enteral feeding intolerance (EFI).\n\nUlimorelin is being redeveloped for the treatment of EFI in Intensive Care Unit (ICU) patients. After showing promise in earlier trials, it failed in two late-stage studies in other disease conditions. Greater understanding is needed of underlying PK-PD relationships than currently exists in order to correct deficits in prior studies and to design effective doses for ICU patients. This study seeks to assess fundamental pharmacokinetics (PK; how the body affects the drug), pharmacodynamics (PD; how the drug affects the body), tolerability, and safety of ulimorelin. This study in being done in healthy volunteers where greater information can be obtained than in a heterogeneous and sick patient population. Unlike prior studies, this study will provide data on the activity of sustained, higher, and more frequent drug doses, and most importantly, will specifically elucidate the required free drug concentrations to produce an increase in growth hormone and gastric emptying (the PD effects). Complex protein binding in the blood inactivates ulimorelin, as only free drug exerts an effect. Prior studies incorrectly focused on the levels of total drug, leading to incorrect dose selection. \n\nUlimorelin is expected to restore normal stomach emptying and re-enable enteral feeding. The study will be conducted at Quotient Clinical, a clinical research organisation on behalf of Lyric Pharmaceuticals Inc and will consist of single increasing doses between 600 and 2400 μg/kg of study drug or matching placebo, and multiple increasing doses of between 300 and 1200 μg/kg of study drug or matching placebo, every 8 hours for 7 days.\n
REC name
Wales REC 1
REC reference
15/WA/0195
Date of REC Opinion
15 Jun 2015
REC opinion
Further Information Favourable Opinion