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 defined as platelet count below 75.0 10*9/L, von Willebrand disease). 8. Pregnant or breastfeeding women. 9. Known and documented moderate or severe hepatic impairement (e.g. Child-Pugh Score B or C). 10. Concomitant diseases (e.g. advanced liver cirrhosis, mental illness, neurodegenerative disease, terminal malignancy, etc.) or conditions (e.g. inability to communicate well with the investigator in the local language, inability to consent) that in the opinion of the investigator, may prevent subject from complying with study requirements or may be a confounder for the study interpretation. |
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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
| 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 | 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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End of Study will be a site visit scheduled 30-37 days after study treatment administration |
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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 | 2 |
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 |