A Medical Research Study to Evaluate the Effects of ACT-246475 in Adults With Heart Attack

Acute Myocardial Infarction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03487445
• Other study ID #: ID-076A202
• Secondary ID: 2018-000765-36
• Status: Completed
• Phase: Phase 2
• Start date: July 10, 2018
• Est. completion date: November 10, 2018

Study information

• Verified date: November 2022
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to find out how fast a drug called selatogrel (ACT-246475) can prevent platelets from binding together. This study will also help to find out more about the safety of this new drug. The drug selatogrel (ACT-246475) will be used in 2 different doses (8 mg or 16 mg) and will be administered in the thigh.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: November 10, 2018
• Est. primary completion date: November 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Infarction
• Myocardial Infarction

Intervention

Drug:
• Selatogrel 8 mg
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%.
• Selatogrel 16 mg
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.

Locations

Country	Name	City	State
Belgium	OLV Ziekenhuis Aalst	Aalst
Belgium	UZLeuven	Leuven
Israel	Galilee Medical Center	Nahariya
Switzerland	Universitätsspital Basel	Basel
Switzerland	University Hospital Bern	Bern
Switzerland	Cardiocentro Ticino	Lugano

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Countries where clinical trial is conducted

Belgium,  Israel,  Switzerland, 

References & Publications (3)

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. — View Citation

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. Epub 2006 Apr 18. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants (Per-protocol Subgroup) With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation	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.	30 minutes after the administration of the subcutaneous injection
Other	Number of Participants With a Pharmacodynamic Response Within the First Hour as Assessed by the Inhibition of Platelet Aggregation	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.	pre-dose, 15, 30 and 60 minutes after the administration of the subcutaneous injection
Other	Absolute Platelet Reactivity (P2Y12 Reaction Units) Over Time	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).	pre-dose, 15, 30 and 60 minutes after administration of the subcutaneous injection
Other	Maximum Selatogrel Plasma Concentration (Cmax)	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
Other	Time to Reach Maximum Selatogrel Plasma Concentration (Tmax)	Time after subcutaneous injection to reach the maximum observed selatogrel plasma concentration (Cmax).	pre-dose, 15, 30 and 60 minutes and 8 hours after the administration of the subcutaneous injection
Primary	Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation	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.	30 minutes after the administration of the subcutaneous injection