- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03487445
A Medical Research Study to Evaluate the Effects of ACT-246475 in Adults With Heart Attack
A Multi-center, Open-label, Randomized, Study to Assess the Onset of Platelet Aggregation Inhibition After a Single Subcutaneous Injection of ACT-246475 in Adults With Acute Myocardial Infarction
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This study is planned in patients presenting with Acute Myocardial Infarction (AMI) scheduled for an invasive strategy. Platelet activation and thrombus formation play a pivotal role in the pathophysiology of acute coronary syndrome. Early platelet inhibition has been shown to reduce the risk of recurrent events after a myocardial infarction.
The screening period starts when the participant provides informed consent and ends with participant's randomization. Eligible participants had an acute myocardial infarction (AMI; ST-segment elevation myocardial infarction [STEMI] or non-ST-elevation myocardial infarction [NSTEMI]), a life-threatening condition, and will therefore fulfill the ICH-GCP definition of vulnerable subjects ("persons in emergency situations"). Accordingly, a specific process for obtaining consent in compliance with local regulations and approved by the independent ethics committee will be implemented.
The study will be performed during a participant's hospital stay related to the qualifying AMI.
Standard treatment of AMI is allowed including anticoagulants. Ticagrelor will be the only oral P2Y12 receptor antagonist allowed to be initiated during the study and its administration will be possible only after selatogrel administration. Use of fibrinolytics or GPIIb/IIIa inhibitors will be prohibited unless required for bail-out. All other standard-of-care treatments for AMI will be allowed without restriction.
The treatment period starts with the participant's randomization and ends after the end-of-study assessments, approximately 48 hours after the administration of a single study treatment dose.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Aalst, Belgium, 9300
- OLV Ziekenhuis Aalst
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Leuven, Belgium, 3000
- UZLeuven
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Nahariya, Israel, 22100
- Galilee Medical Center
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Basel, Switzerland, 4031
- Universitätsspital Basel
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Bern, Switzerland, 3010
- University Hospital Bern
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Lugano, Switzerland, 6900
- Cardiocentro Ticino
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Main Inclusion Criteria:
- Informed consent obtained prior to any study-mandated procedure,
- Males aged from 18 to 85 and postmenopausal females aged up to 85 years,
- Onset of symptoms of AMI of more than 30 min and less than 6 hours prior to randomization,
- Subjects presenting a type I AMI including STEMI or NSTEMI.
Main Exclusion Criteria:
- Cardiogenic shock or severe hemodynamic instability,
- Cardiopulmonary resuscitation,
- Loading dose of any oral P2Y12 receptor antagonist prior to randomization,
- Planned fibrinolytic therapy or any fibrinolytic therapy administered within 24 h prior to randomization,
- Known platelet disorders (e.g., thromboasthenia, thrombocytopenia, von Willebrand disease).
- Active internal bleeding, or bleeding diathesis or conditions associated with high risk of bleeding.
- Known clinically important anemia.
- Oral anticoagulation therapy within 7 days prior to randomization
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Selatogrel 8 mg
Selatogrel (ACT-246475) is given as a single subcutaneous dose of 8 mg administered in a volume of 0.8 mL.
Administration will be performed at the investigational site by qualified personnel.
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Selatogrel is a reversible P2Y12 receptor antagonist for subcutaneous administration.
It is supplied in sealed glass vials at a strength of 20 mg.
The vials with ACT-246475A (hydrochloride salt of ACT-246475) will be reconstituted with 1 mL of water and further diluted with 1 mL sodium chloride (NaCl) 0.9%.
Other Names:
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Experimental: Selatogrel 16 mg
Selatogrel (ACT-246475) is given as a single subcutaneous dose of 16 mg administered in a volume of 0.8 mL.
Administration will be performed at the investigational site by qualified personnel.
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Selatogrel is a reversible P2Y12 receptor antagonist for subcutaneous administration.
It is supplied in sealed glass vials at a strength of 20 mg.
The vials with ACT-246475A (hydrochloride salt of ACT-246475) will be reconstituted with 1 mL of water for injection.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation
Time Frame: 30 minutes after the administration of the subcutaneous injection
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The pharmacodynamic response was determined by measuring the inhibition of platelet aggregation, using the VerifyNow® assay.
The VerifyNow® is a point-of-care test measuring platelet reactivity.
The results are expressed as P2Y12 reaction units (PRU).The target of 100 PRU corresponds to 80% inhibition of ADP-induced platelet aggregation.
A participant with a PRU less than 100 at 30 minutes post-dose was counted as a participant that had a pharmacodynamic response.
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30 minutes after the administration of the subcutaneous injection
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants (Per-protocol Subgroup) With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation
Time Frame: 30 minutes after the administration of the subcutaneous injection
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The pharmacodynamic response was determined by measuring the inhibition of platelet aggregation, using VerifyNow®.
The VerifyNow® is a point-of-care test measuring platelet reactivity.
The results are expressed as P2Y12 reaction units (PRU).
The target of 100 PRU corresponds to 80% inhibition of ADP-induced platelet aggregation.
A participant with a PRU of less than 100 starting at 30 minutes post-dose was counted as a participant that had a pharmacodynamic response.
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30 minutes after the administration of the subcutaneous injection
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Number of Participants With a Pharmacodynamic Response Within the First Hour as Assessed by the Inhibition of Platelet Aggregation
Time Frame: pre-dose, 15, 30 and 60 minutes after the administration of the subcutaneous injection
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The purpose of this supportive analysis was to assess the effect when relaxing the time of a PRU < 100, i.e., considering as a response a PRU < 100 at 15, 30 or 60 min.
post injection.
The pharmacodynamic response was determined by measuring the inhibition of platelet aggregation, using the VerifyNow® assay.
The VerifyNow® is a point-of-care test measuring platelet reactivity.
The results are expressed as P2Y12 reaction units (PRU).The target of 100 PRU corresponds to 80% inhibition of ADP-induced platelet aggregation.
A participant with a PRU less than 100 post-dose was counted as a participant that had a pharmacodynamic response.
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pre-dose, 15, 30 and 60 minutes after the administration of the subcutaneous injection
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Absolute Platelet Reactivity (P2Y12 Reaction Units) Over Time
Time Frame: pre-dose, 15, 30 and 60 minutes after administration of the subcutaneous injection
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The pharmacodynamic response assessed by the inhibition of adenosine diphosphate (ADP)-mediated platelet aggregation was determined by measuring the inhibition of platelet aggregation, using VerifyNow®.
The VerifyNow® is a point-of-care test.
The results are expressed as P2Y12 reaction units (PRU).
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pre-dose, 15, 30 and 60 minutes after administration of the subcutaneous injection
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Maximum Selatogrel Plasma Concentration (Cmax)
Time Frame: pre-dose, 15, 30 and 60 minutes and 8 hours after the administration of the subcutaneous injection
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The Cmax is the peak concentration of selatogrel in the plasma after subcutaneous injection. The pharmacokinetic parameters of selatogrel (ACT-246475) were derived by non-compartmental analyses of the plasma concentration-time profiles. |
pre-dose, 15, 30 and 60 minutes and 8 hours after the administration of the subcutaneous injection
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Time to Reach Maximum Selatogrel Plasma Concentration (Tmax)
Time Frame: pre-dose, 15, 30 and 60 minutes and 8 hours after the administration of the subcutaneous injection
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Time after subcutaneous injection to reach the maximum observed selatogrel plasma concentration (Cmax).
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pre-dose, 15, 30 and 60 minutes and 8 hours after the administration of the subcutaneous injection
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Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Gurbel PA, Bliden KP, Butler K, Antonino MJ, Wei C, Teng R, Rasmussen L, Storey RF, Nielsen T, Eikelboom JW, Sabe-Affaki G, Husted S, Kereiakes DJ, Henderson D, Patel DV, Tantry US. Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: the RESPOND study. Circulation. 2010 Mar 16;121(10):1188-99. doi: 10.1161/CIRCULATIONAHA.109.919456. Epub 2010 Mar 1.
- Jernberg T, Payne CD, Winters KJ, Darstein C, Brandt JT, Jakubowski JA, Naganuma H, Siegbahn A, Wallentin L. Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease. Eur Heart J. 2006 May;27(10):1166-73. doi: 10.1093/eurheartj/ehi877. Epub 2006 Apr 18.
- Parodi G, Bellandi B, Valenti R, Migliorini A, Marcucci R, Carrabba N, Giurlani L, Gensini GF, Abbate R, Antoniucci D. Comparison of double (360 mg) ticagrelor loading dose with standard (60 mg) prasugrel loading dose in ST-elevation myocardial infarction patients: the Rapid Activity of Platelet Inhibitor Drugs (RAPID) primary PCI 2 study. Am Heart J. 2014 Jun;167(6):909-14. doi: 10.1016/j.ahj.2014.03.011. Epub 2014 Apr 4.
- Sinnaeve P, Fahrni G, Schelfaut D, Spirito A, Mueller C, Frenoux JM, Hmissi A, Bernaud C, Ufer M, Moccetti T, Atar S, Valgimigli M. Subcutaneous Selatogrel Inhibits Platelet Aggregation in Patients With Acute Myocardial Infarction. J Am Coll Cardiol. 2020 May 26;75(20):2588-2597. doi: 10.1016/j.jacc.2020.03.059.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ID-076A202
- 2018-000765-36 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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