Ph2 Study to assess temanogrel effect in patients undergoing PCI
Research type
Research Study
Full title
A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, and Effect on Microvascular Obstruction of Temanogrel in Subjects Undergoing Percutaneous Coronary Intervention.
IRAS ID
291769
Contact name
Diana Gorog
Contact email
Sponsor organisation
Arena Pharmaceuticals, Inc.
Eudract number
2020-000238-16
Duration of Study in the UK
1 years, 3 months, 0 days
Research summary
The purpose of the study is to assess whether an investigational drug called temanogrel (also referred to as the ‘study drug’) works to prevent or reduce blockages in the small blood vessel(s) that supply the heart with blood, termed microvascular obstruction (MVO). These small blockages can occur during or after an interventional procedure, called percutaneous coronary intervention (PCI), that is performed in order to resolve the existing blockage in the coronary arteries i.e. bigger blood vessel(s) of the heart.
The presence of MVO post-PCI has been associated with worse clinical outcomes including mortality and hospitalization for heart failure, related to suboptimal cardiac function and recovery in the days and months following the PCI procedure
Several treatment options have been explored including the use of vasodilators and antiplatelet agents; however, clinical efficacy data from these interventions is limited and currently no treatment has been demonstrated to be beneficial for prevention or treatment of MVO following PCI. Therefore, there is an unmet need for safe and effective agents to prevent and treat MVO in the PCI setting, resulting in improved cardiac functional recovery and clinical outcomes.
Temanogrel, the study drug, is designed to prevent or stop serotonin from narrowing blood vessels and forming clumps of platelets leading to blood clots during and after PCI. It is hoped that by stopping these actions of serotonin, MVO can be prevented/treated and there will be an improvement in blood flow within the heart, therefore improving recovery outcomes following PCI.
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study to be conducted in 2 stages (Stage A and Stage B). Approximately 99 subjects are planned to be enrolled in this study. In Stage A, 2 cohorts are planned and 6 subjects will be enrolled in each cohort (4 temanogrel:2 placebo per cohort). One additional cohort (4 temanogrel:2 placebo per cohort) may be enrolled to explore an additional dose if deemed appropriate based upon data reviews of prior cohorts. In Stage B, approximately 87 subjects are planned to be enrolled (29 subjects in each of the 2 temanogrel treatment groups and the placebo group).Summary of Results
A key limitation of the study is small sample size due to early termination of the study. Due to this limitation, efficacy data are inconclusive. PK data were summarized for a small number of subjects. No formal statistical evaluation of primary and key secondary efficacy endpoints has been performed. Plasma exposures of temanogrel increased less than dose proportionally across the 20 and 40 mg IV dose range. Exposures of AR295980 and AR295981 were lower than temanogrel.
Although the study was limited in the assessment of the efficacy and the primary study endpoint as described above, temanogrel (20 mg and 40 mg) appeared to be safe and well tolerated in participants undergoing PCI.REC name
East Midlands - Derby Research Ethics Committee
REC reference
21/EM/0010
Date of REC Opinion
10 Feb 2021
REC opinion
Further Information Favourable Opinion