E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Microvascular Obstruction |
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E.1.1.1 | Medical condition in easily understood language |
Microvascular Obstruction |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10079682 |
E.1.2 | Term | Microvascular occlusion |
E.1.2 | System Organ Class | 100000004866 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To assess the effect of temanogrel on MVO following PCI |
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E.2.2 | Secondary objectives of the trial |
1. To assess the effect of temanogrel on selected coronary physiology indices and angiographic measures following PCI 2. To assess the effect of temanogrel on myocardial injury following PCI; 3. To assess the pharmacokinetics (PK) of temanogrel and its active metabolites AR295980 (M1) and AR295981 (M2) in subjects undergoing PCI; 4. To assess the safety and tolerability of temanogrel in subjects undergoing PCI |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
APD791-202 Amendment 2.0, Substudy A-Phase 2 (SSA-P2), Site Specific Addendum 1.0: - The primary endpoint of Study APD791-202 is based on a quantitative assessment of the coronary microcirculation using index of microcirculatory resistance (IMR). IMR is based on thermodilution curves obtained in triplicate from rapid injections of room temperature saline in the coronary artery during hyperemia, which is induced by intravenous administration of adenosine.
- The aim of this substudy is to investigate changes in R and MRR from Baseline (prior to percutaneous coronary intervention [PCI] and administration of study treatment) to Pre-PCI (following study treatment administration ie, post-drug but pre-PCI) and Post-PCI (following PCI). These assessments will be performed immediately following measurements of IMR at sites participating in this substudy using the same Coroventis software utilized in the parent APD791-202 study. It is anticipated this may provide assessment of the coronary microcirculation that is complementary to, but distinct from, IMR. Specifically, these measures may provide insight into the effect of temanogrel on microcirculation at resting conditions, which may not be apparent during adenosine-induced hyperemia utilized when performing IMR assessments, as well as providing an absolute assessment of microvascular resistance.
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E.3 | Principal inclusion criteria |
- Stable angina patients referred for elective percutaneous coronary intervention (PCI), or non-ST-elevation myocardial infarction (NSTEMI) and unstable angina (UA) patients undergoing PCI at least 12 hours after diagnosis for NSTEMI/UA. NSTEMI/UA patients are to be consistently hemodynamically stable until the time of PCI and have a thrombolysis in myocardial infarction Grade 3 on the diagnostic angiography prior to PCI - Target lesions for PCI must appear suitable for stenting as confirmed on the diagnostic angiography prior to PCI. The lesion must be located in a ≥2.75 millimeter (mm) diameter coronary artery; the lesion must also be ≥18 mm long and require the use of one or more stents that in total must be ≥20 mm long. Acceptable lesions cannot be in the left main artery or in a vein or arterial graft, or be a chronic total occlusion or in-stent restenosis. Two or more sequential lesions may be treated in the same artery, as long as they are treated in the same session and at least one of the lesions meets inclusion criteria - Both men and women participants agree to use a highly effective method of birth control throughout the entire study period, from informed consent through the adverse event reporting period, if the possibility of conception exists |
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E.4 | Principal exclusion criteria |
- Planned or anticipated use of rotational atherectomy/ablation or shockwave therapies during the PCI procedure; - Any history of stroke, head injury, seizure, intracranial bleeding, or intracranial aneurysm; - Transient ischemic attack within the 6 months prior to Screening; - History of major trauma, major surgery, and/or clinically significant hemorrhage within the last 6 months of Screening; - NSTEMI/UA with subsequent cardiac troponin levels that are increasing (not stable or dropping) as shown by the 2 most recent measures after diagnosis of NSTEMI/UA and prior to randomization; - Any ST-elevation myocardial infarction (STEMI) within 10 days of Screening or STEMI within the target vessel territory within the last 6 months of Screening (eg, a patient with a NSTEMI because of a lesion in a diagonal may not be included if there is a history of anterior STEMI due to left anterior descending artery lesion that occurred within the last 6 months); - Known history of heart failure. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change in IMR from Baseline to Post-PCI
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Baseline, pre-PCI, post-PCI. |
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E.5.2 | Secondary end point(s) |
1. Change from Baseline to Post-PCI for the following assessments: • Coronary physiology indices (coronary flow reserve [CFR], fractional flow reserve [FFR]), • Angiographic measures (corrected thrombolysis in myocardial infarction frame count [cTFC], TFG, thrombolysis in myocardial infarction myocardial perfusion grade [TMPG]), • Myocardial injury markers (creatine kinase [CK], creatine kinase-myocardial band [CK-MB], cTn); 2. Incidence of Procedural Myocardial Injury; 3. Observed Maximum Plasma Concentration (Cmax) of Temanogrel and its Metabolites; 4. Safety and tolerability of temanogrel |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-4. Baseline, pre-PCI, post-PCI. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
United States |
Sweden |
Netherlands |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |