E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
stable coronary artery disease |
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E.1.1.1 | Medical condition in easily understood language |
Coronary artery disease is when a plaque builds up inside the coronary arteries. A plaque is made up of fat, white blood cells, and other substances found in the blood. |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011078 |
E.1.2 | Term | Coronary artery disease |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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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 |
The primary objective of the study is to characterize inhibition of platelet aggregation (IPA) relative to placebo after a single s.c. injection of ACT-246475 either in the thigh or in the abdomen at 2 different doses in subjects with stable coronary artery disease (CAD) receiving conventional background oral antiplatelet therapy (e.g., acetylsalicylic acid, P2Y12 receptor antagonists). |
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E.2.2 | Secondary objectives of the trial |
• To assess the pharmacokinetics (PK) of ACT-246475. • To assess the impact of the injection site location (thigh vs abdomen) on the PK and pharmacodynamics (PD) of ACT-246475. • To investigate the impact of concomitant drug use, age, sex, and other covariates on the PK and PD of ACT-246475. • To investigate the safety and tolerability of ACT-246475. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent prior to any study-mandated procedure. 2. Male and female subjects aged from 18–85 years, inclusive. 3. For women of childbearing potential: Negative urine pregnancy test at Visit 1 and at Visit 2 before randomization. 4. Stable CAD defined by the presence of any of the following conditions: a. History of CAD with coronary artery stenosis on coronary angiogram ≥ 50%. b. Previously documented myocardial infarction occurring more than 3 months prior to randomization. 5. Antiplatelet background therapy stable for at least 1 month prior to randomization. 6. Body weight ≥ 40.0 kg (88.2 lbs). |
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E.4 | Principal exclusion criteria |
1. Acute coronary syndrome, percutaneous coronary intervention or any intervention for peripheral artery disease within 3 months prior to randomization. 2. Acute ischemic stroke or transient ischemic attack (TIA) within 3 months prior to randomization. 3. Active internal bleeding, or medical history of recent (< 1 month) bleeding disorders or conditions associated with high risk of bleeding (e.g., clotting disturbances, gastrointestinal bleed, hemoptysis). 4. Hemoglobin ≤ 10 g/dL at screening. 5. Loss of at least 250 mL of blood within 3 months of screening. 6. Use of anticoagulants (oral, parenteral) or fibrinolytic therapy within 24 h prior to screening (Visit 1). 7. Known platelet disorders (e.g., thrombasthenia, thrombocytopenia, von Willebrand disease). 8. Pregnant or breastfeeding women. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary PD endpoint is the PD response that is defined for each subject as a P2Y12 Reaction Units < 100 starting 30 min after injection and lasting for at least 3 h, as measured via the VerifyNow® assay. This corresponds to inhibition of ADP-induced platelet aggregation (IPA) > 80%. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
starting 15 minutes after injection, for 24 h |
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E.5.2 | Secondary end point(s) |
The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles. PK endpoints include: • Cmax. • tmax. • The AUC from time zero to 24 h time point (AUC0–24h). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
starting 15 minutes after injection, for 24 h |
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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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
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 |
Canada |
Denmark |
France |
Germany |
Netherlands |
Singapore |
Sweden |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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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safety follow-up telephone call 28-35 days after LSLV |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |