Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Selatogrel
ACT-246475 · 7 trials · 6 indications
The clinical status will be assessed using a 6-point ordinal scale after any study treatment self-administration. Only the worst clinical outcome will be retained as the primary efficacy outcome. The 6 mutually exclusive outcomes ranked from worst to best are: 1. Death (all causes), within 7 days after study treatment administration. 2. Acute myocardial infarction with compromised electro-hemodynamics, within 2 days after study treatment administration. 3. ST-Elevation Myocardial Infarction (STEMI), within 2 days after study treatment administration. 4. High-risk Non-ST-Elevation Myocardial Infarction (NSTEMI), within 2 days after study treatment administration. 5. NSTEMI with peak cardiac troponin greater than 10 times upper limit of normal, within 2 days after study drug administration. 6. None of the above
The number of: * Type 3 treatment-emergent bleeding events and * Type 5 treatment-emergent bleeding events will be assessed according to the Bleeding Academic Research Consortium (BARC) definition (Mehran et al. 2011), within 2 days after study treatment administration. The Bleeding Academic Research Consortium (BARC) definitions are: * Type 3, bleeding is divided into 3 categories, a through c, and includes clinical, laboratory, and/or imaging evidence of bleeding with specific healthcare provider responses. * Type 5, bleeding is fatal.
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.
The plasma selatogrel PK parameters will be derived by non compartmental analysis of the concentration-time profiles
The plasma selatogrel PK parameters will be derived by non compartmental analysis of the concentration-time profiles
The measured individual plasma concentrations of selatogrel will be used to directly obtain Cmax
The measured individual plasma concentrations of selatogrel will be used to directly obtain tmax
The plasma selatogrel PK parameters will be derived by non compartmental analysis of the concentration-time profiles
The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles
The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles
The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles
The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles
The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles
Cumulative amount of total 14C-radioactivity excreted in urine and feces will be calculated by summing up the amount of total 14C-radioactivity of the samples excreted in each collection interval
\- IPA%\[MPA\] will be calculated as mean change in percentage from baseline for each time point.
\- IPA%\[PRU\] will be calculated as mean change in percentage from baseline for each time point. Treatment A1: single s.c. dose administration of ACT-246475-matching placebo followed by a single oral dose of clopidogrel (600 mg). Treatment A2: single s.c. dose administration (16 mg) of ACT-246475 followed by a single oral dose of clopidogrel (300 mg). Treatment B1: single s.c. dose administration of ACT-246475-matching placebo followed by a single oral dose of prasugrel (60 mg). Treatment B2: single s.c. dose administration (16 mg) of ACT-246475 followed by a single oral dose of prasugrel (60 mg). Treatment C1: single s.c. dose administration of ACT-246475-matching placebo followed by a single oral dose of ticagrelor (180 mg). Treatment B2: single s.c. dose administration (16 mg) of ACT-246475 followed by a single oral dose of ticagrelor (180 mg).
| Arm | Type | Description |
|---|---|---|
| Selatogrel | EXPERIMENTAL | Study treatment administration may occur at any time between the randomization visit and the final study visit when the participant experiences symptoms suggestive of an acute myocardial infarction. Study treatment administration triggers protocol pre-defined assessments or visits. |
| Placebo | PLACEBO_COMPARATOR | Study treatment administration may occur at any time between the randomization visit and the final study visit when the participant experiences symptoms suggestive of an acute myocardial infarction. Study treatment administration triggers protocol pre-defined assessments or visits. |
| Selatogrel 8 mg | EXPERIMENTAL | 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. |
| Selatogrel 16 mg | EXPERIMENTAL | 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. |
| Treatment period A | EXPERIMENTAL | Treatment A1: saline 0.9% followed by Treatment A2: ACT-246475 |
| Treatment period B | EXPERIMENTAL | Treatment B1: rifampicin followed by Treatment B2: ACT-246475 |
| Treatment and observation period | EXPERIMENTAL | On Day 1, the subjects will receive a single s.c. dose of 16 mg 14C-radiolabeled ACT-246475 in the fasted state. Subjects will be followed by an observation period of 3 days (72 h) during which blood, urine, and feces samples will be collected. |
| Part A: Group 1 | EXPERIMENTAL | Clopidogrel will be administered 0.5 h after ACT-246475 or placebo, i.e., at the time of tmax |
| Part A: Group 2 | EXPERIMENTAL | Clopidogrel will be administered 12 h after ACT-246475 or placebo |
| Part A: Group 3 | EXPERIMENTAL | Any time interval up to 24 h between the administration of ACT-246475 or placebo and clopidogrel may be studied |
| Part B: Group 1 | EXPERIMENTAL | Prasugrel will be administered 12 h after ACT-246475 or placebo |
| Part B: Group 2 | EXPERIMENTAL | Any time interval up to 24 h between the administration of ACT-246475 or placebo and prasugrel may be studied |
| Part B: Group 3 | EXPERIMENTAL | Any time interval up to 24 h between the administration of ACT-246475 or placebo and prasugrel may be studied |
| Part C: Group 1 | EXPERIMENTAL | Ticagrelor will be administered 0.5 h after ACT-246475 or placebo, i.e., at the time of tmax |
| Part C: Group 2 | EXPERIMENTAL | Any time interval up to 24 h between the administration of ACT-246475 or placebo and ticagrelor may be studied |
| Part C: Group 3 | EXPERIMENTAL | Any time interval up to 24 h between the administration of ACT-246475 or placebo and ticagrelor may be studied |
| Name | Type | Description |
|---|---|---|
| Selatogrel | COMBINATION_PRODUCT | Selatogrel is a reversible P2Y12 receptor antagonist for subcutaneous administration. Selatogrel will be administered as a liquid formulation in a sealed prefilled syringe in an autoinjector forming an integral ready-to-use, single-dose drug delivery system. Participants will self-administer 16 mg of selatogrel subcutaneously with the autoinjector upon occurrence of symptoms suggestive of an acute myocardial infarction. Self-administration encompasses the use of the autoinjector by another person (e.g., partner, close relative, friend, caregiver) who may be called for help during the emergency situation of a suspected AMI. |
| Placebo | COMBINATION_PRODUCT | Placebo will be administered as a liquid formulation in a sealed prefilled syringe in an autoinjector forming an integral ready-to-use, single-dose drug delivery system. Participants will self-administer placebo subcutaneously with the autoinjector upon occurrence of symptoms suggestive of an acute myocardial infarction. Self-administration encompasses the use of the autoinjector by another person (e.g., partner, close relative, friend, caregiver) who may be called for help during the emergency situation of a suspected AMI. |
| Selatogrel 8 mg | DRUG | 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 | DRUG | 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. |
| Matching placebo | COMBINATION_PRODUCT | A single dose of placebo will be administered as a liquid formulation from a sealed prefilled syringe in an autoinjector forming an integral ready-to-use, single-dose drug delivery system. |
| Saline | DRUG | Single i.v. infusion of 100 mL saline 0.9% for 30 min |
| ACT-246475 | DRUG | Single s.c. dose of 4 mg ACT-246475 in the thigh under fasting conditions |
| Rifampicin | DRUG | Single i.v. infusion of 600 mg rifampicin (100 mL) for 30 min |
| Clopidogrel | DRUG | Tablet for oral administration (300 or 600 mg) |
| Prasugrel | DRUG | Tablet for oral administration (60 mg) |
| Ticagrelor | DRUG | Tablet for oral administration (180 mg) |
Main Inclusion Criteria: * Confirmed diagnosis of symptomatic type 1 acute myocardial infarction (AMI) ST-Elevation Myocardial Infarction (STEMI) or Non-ST-Elevation Myocardial Infarction (NSTEMI), no longer than 4 weeks prior to randomization. * Diagnosis of multivessel coronary artery disease def...
ACT-246475 is a small molecule drug candidate developed by Viatris Inc. It has been studied in Phase 1 clinical trials involving healthy volunteers. The specific therapeutic indications for ACT-246475 have not been publicly disclosed.
ACT-246475 is being developed by Viatris Inc., which trades on the Nasdaq under the ticker symbol VTRS. Viatris is the sponsor of the clinical program for this small molecule candidate.
ACT-246475 is in Phase 1 clinical development. All three of its recorded trials are Phase 1 studies, and all three have been completed. There are currently no active trials for ACT-246475 listed.
ACT-246475 has been evaluated in three completed Phase 1 trials: NCT03814200, which studied the effect of rifampicin on ACT-246475 in 14 healthy subjects in the Netherlands; NCT03593278, which evaluated ACT-246475 fate in 6 healthy male subjects in Germany; and NCT03430661, which investigated interactions between ACT-246475 and clopidogrel, prasugrel, and ticagrelor in 77 healthy subjects in the United States.
Across the three completed Phase 1 trials of ACT-246475, a total of 97 participants have been enrolled. Enrollment ranged from 6 participants in NCT03593278 to 77 participants in NCT03430661. All trials enrolled healthy volunteers rather than patients with a specific disease.
Yes. The ACT-246475 Phase 1 trials were randomized and double blind, and they used a controlled design. The studies enrolled healthy volunteers, and none of the trials used biomarker-based patient selection.