Stable Coronary Artery Disease
Conditions
Keywords
Chronic coronary syndrome
Brief summary
The goal of this study is to find out if a drug called selatogrel (ACT-246475) can prevent platelets from binding together when administered by an injection under the skin in the thigh or in the belly. Another goal is to know how fast and for how long selatogrel (ACT-246475) works and if there is a difference if the drug is injected in the thigh or in the belly. This study will also help to find out more about the safety of this new drug.
Detailed description
To investigate the pharmacodynamic (PD) and pharmacokinetic (PK) properties of selatogrel in patients with atherosclerotic disease, the present study will be conducted in patients with chronic coronary syndromes (CCS). Assessment in a population of patients with CCS allows better control and stability of concomitant treatments, and therefore more accurate characterization of the pharmacodynamic and pharmacokinetic profiles of selatogrel in the presence of background antiplatelet therapies. The study will have 3 periods: a screening period of up to 21 days prior to randomization, a treatment period of 2 days from randomization (Day 1) to 24 hours post dose (Day 2), and a follow-up period from Day 3 to the safety follow-up telephone call 28 to 35 days after single administration of study drug (End-of-Study).
Interventions
DRUGSelatogrel
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) or matching placebo will be reconstituted with 1 mL of water for injection. Further dilution with 1 mL sodium chloride (NaCl) 0.9% will be performed for preparation of the dose of 8 mg selatogrel.
DRUGPlacebo
Matching placebo for subcutaneous administration.
Sponsors
Viatris Innovation GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blinding will apply to treatment (ACT-246475 vs placebo). The dose (8 mg vs 16 mg) will be single blinded (subject blinded). The site for the sub-cutaneous injection (thigh vs abdomen) will not be blinded.
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Main 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 Coronary artery disease (CAD) defined by the presence of any of the following conditions: 1. History of CAD with coronary artery stenosis on coronary angiogram ≥50%. 2. 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). Main
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation | From 15 minutes after administration of the subcutaneous injection up to 24 hours | 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 from 30 minutes after the administration of study treatment and lasting for at least 3 hours was considered a "responder". |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Selatogrel Plasma Concentration (Cmax) | Pre-dose, and from 15 minutes after administration of the subcutaneous injection up to 24 hours | 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. |
| Time to Reach Maximum Selatogrel Plasma Concentration (Tmax) | Pre-dose, and from 15 minutes after administration of the subcutaneous injection up to 24 hours | Time after subcutaneous injection to reach the maximum observed selatogrel plasma concentration (Cmax). |
| Area Under the Plasma Concentration-time Curve of Selatogrel From Time Zero to 24 Hour Time Point (AUC0-24) | Pre-dose, and from 15 minutes after administration of the subcutaneous injection up to 24 hours post-dose | The area under the plasma concentration-time curve is the integral of the concentration-time curve after subcutaneous injection of selatogrel. The plasma pharmacokinetic parameters of selatogrel (ACT-246475) were derived by non-compartmental analyses of the plasma concentration-time profiles. |
Countries
Canada, Denmark, Germany, Netherlands, Singapore, Sweden, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Viatris Innovation GmbH
Participant flow
Recruitment details
The study was conducted between 24 Jan and 18 Sep 2018. Twenty sites in 8 countries screened 362 participants and 17 sites randomized 346 participants.
Pre-assignment details
Of the 16 participants not randomized: 9 were ineligible; 4 withdrew consent; 1 was lost to follow-up, 1 was not randomized based on the physician's decision and 1 didn't complete screening within the protocol-defined window.
Participants by arm
| Arm | Count |
|---|---|
| Selatogrel 8 mg Selatogrel (ACT-246475) 8 mg was administered as a single subcutaneous dose. | 114 |
| Selatogrel 16 mg Selatogrel (ACT-246475) 16 mg was administered as a single subcutaneous dose. | 115 |
| Placebo Matching placebo was administered as a single subcutaneous dose. | 116 |
| Total | 345 |
Baseline characteristics
| Characteristic | Selatogrel 8 mg | Total | Placebo | Selatogrel 16 mg |
|---|---|---|---|---|
| Age, Categorical Full analysis set <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Full analysis set >=65 years | 66 Participants | 194 Participants | 61 Participants | 67 Participants |
| Age, Categorical Full analysis set Between 18 and 65 years | 48 Participants | 151 Participants | 55 Participants | 48 Participants |
| Age, Categorical Per-protocol analysis set <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Per-protocol analysis set >=65 years | 55 Participants | 159 Participants | 50 Participants | 54 Participants |
| Age, Categorical Per-protocol analysis set Between 18 and 65 years | 41 Participants | 120 Participants | 43 Participants | 36 Participants |
| Age, Continuous Full analysis set | 64.8 years STANDARD_DEVIATION 9.4 | 65.0 years STANDARD_DEVIATION 9 | 64.9 years STANDARD_DEVIATION 9.1 | 65.2 years STANDARD_DEVIATION 8.5 |
| Age, Continuous Per-protocol analysis set | 64.4 years STANDARD_DEVIATION 9.7 | 64.9 years STANDARD_DEVIATION 9.2 | 65.1 years STANDARD_DEVIATION 9.2 | 65.3 years STANDARD_DEVIATION 8.8 |
| Body Mass Index Full analysis set | 29 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5 | 30 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5 | 31 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5 | 29 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 6 |
| Body Mass Index Per-protocol analysis set | 29 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5 | 29 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5 | 30 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5 | 29 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5 |
| Ethnicity (NIH/OMB) Full analysis set Hispanic or Latino | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Full analysis set Not Hispanic or Latino | 113 Participants | 343 Participants | 116 Participants | 114 Participants |
| Ethnicity (NIH/OMB) Full analysis set Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Per-protocol analysis set Hispanic or Latino | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Per-protocol analysis set Not Hispanic or Latino | 95 Participants | 277 Participants | 93 Participants | 89 Participants |
| Ethnicity (NIH/OMB) Per-protocol analysis set Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Full analysis set American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Full analysis set Asian | 7 Participants | 17 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) Full analysis set Black or African American | 10 Participants | 32 Participants | 9 Participants | 13 Participants |
| Race (NIH/OMB) Full analysis set More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Full analysis set Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Full analysis set Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Full analysis set White | 97 Participants | 296 Participants | 103 Participants | 96 Participants |
| Race (NIH/OMB) Per-protocol analysis set American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Per-protocol analysis set Asian | 7 Participants | 16 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) Per-protocol analysis set Black or African American | 8 Participants | 21 Participants | 7 Participants | 6 Participants |
| Race (NIH/OMB) Per-protocol analysis set More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Per-protocol analysis set Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Per-protocol analysis set Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Per-protocol analysis set White | 81 Participants | 242 Participants | 82 Participants | 79 Participants |
| Region of Enrollment Canada | 1 participants | 6 participants | 4 participants | 1 participants |
| Region of Enrollment Denmark | 0 participants | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Germany | 3 participants | 5 participants | 1 participants | 1 participants |
| Region of Enrollment Netherlands | 25 participants | 65 participants | 21 participants | 19 participants |
| Region of Enrollment Singapore | 4 participants | 8 participants | 2 participants | 2 participants |
| Region of Enrollment Sweden | 7 participants | 30 participants | 10 participants | 13 participants |
| Region of Enrollment United Kingdom | 22 participants | 77 participants | 27 participants | 28 participants |
| Region of Enrollment United States | 52 participants | 153 participants | 51 participants | 50 participants |
| Sex: Female, Male Full analysis set Female | 20 Participants | 69 Participants | 23 Participants | 26 Participants |
| Sex: Female, Male Full analysis set Male | 94 Participants | 276 Participants | 93 Participants | 89 Participants |
| Sex: Female, Male Per-protocol analysis set Female | 16 Participants | 49 Participants | 16 Participants | 17 Participants |
| Sex: Female, Male Per-protocol analysis set Male | 80 Participants | 230 Participants | 77 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 114 | 0 / 115 | 0 / 116 | 1 / 114 | 0 / 115 | 0 / 116 |
| other Total, other adverse events | 36 / 114 | 26 / 115 | 25 / 116 | 13 / 114 | 10 / 115 | 13 / 116 |
| serious Total, serious adverse events | 0 / 114 | 0 / 115 | 0 / 116 | 5 / 114 | 1 / 115 | 1 / 116 |
Outcome results
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 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 from 30 minutes after the administration of study treatment and lasting for at least 3 hours was considered a responder.
Time frame: From 15 minutes after administration of the subcutaneous injection up to 24 hours
Population: Full Analysis Set - all participants that were randomized and who had study treatment administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selatogrel 8 mg | Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation | 102 Count of participants (i.e., responders) |
| Selatogrel 16 mg | Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation | 103 Count of participants (i.e., responders) |
| Placebo | Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation | 18 Count of participants (i.e., responders) |
Comparison: The study aimed at assessing the efficacy of each selatogrel dose versus placebo. The proportion of responders for each of the two doses of selatogrel was compared to placebo.~No imputation was considered for handling missing values.p-value: <0.000197.5% CI: [22.4, 154.8]Chi-squared
Comparison: The study aimed at assessing the efficacy of each selatogrel dose versus placebo. The proportion of responders for each of the two doses of selatogrel was compared to placebo.~No imputation was considered for handling missing values in the main analysis.p-value: <0.000197.5% CI: [23.1, 162.3]Chi-squared
Secondary
Area Under the Plasma Concentration-time Curve of Selatogrel From Time Zero to 24 Hour Time Point (AUC0-24)
The area under the plasma concentration-time curve is the integral of the concentration-time curve after subcutaneous injection of selatogrel. The plasma pharmacokinetic parameters of selatogrel (ACT-246475) were derived by non-compartmental analyses of the plasma concentration-time profiles.
Time frame: Pre-dose, and from 15 minutes after administration of the subcutaneous injection up to 24 hours post-dose
Population: Pharmacokinetic analysis set - all participants that had a selatogrel concentration measurement after administration of study treatment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Selatogrel 8 mg | Area Under the Plasma Concentration-time Curve of Selatogrel From Time Zero to 24 Hour Time Point (AUC0-24) | 716 hours*ng/mL |
| Selatogrel 16 mg | Area Under the Plasma Concentration-time Curve of Selatogrel From Time Zero to 24 Hour Time Point (AUC0-24) | 1358 hours*ng/mL |
Secondary
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.
Time frame: Pre-dose, and from 15 minutes after administration of the subcutaneous injection up to 24 hours
Population: Pharmacokinetic analysis set - all participants that had a selatogrel concentration measurement after administration of study treatment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Selatogrel 8 mg | Maximum Selatogrel Plasma Concentration (Cmax) | 298 ng/mL |
| Selatogrel 16 mg | Maximum Selatogrel Plasma Concentration (Cmax) | 484 ng/mL |
Secondary
Time to Reach Maximum Selatogrel Plasma Concentration (Tmax)
Time after subcutaneous injection to reach the maximum observed selatogrel plasma concentration (Cmax).
Time frame: Pre-dose, and from 15 minutes after administration of the subcutaneous injection up to 24 hours
Population: Pharmacokinetic analysis set - all participants that had a selatogrel concentration measurement after administration of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Selatogrel 8 mg | Time to Reach Maximum Selatogrel Plasma Concentration (Tmax) | 0.52 hour |
| Selatogrel 16 mg | Time to Reach Maximum Selatogrel Plasma Concentration (Tmax) | 0.53 hour |
Post Hoc
Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points
The inhibition of platelet aggregation was determined using VerifyNow®. The VerifyNow® is a point-of-care test measuring platelet reactivity. The results are expressed as P2Y12 reaction units (PRU). After single-dose administration the inhibition of platelet aggregation was measured at pre-defined timepoints to observe the platelet reactivity and aggregation over a 24-hour timeperiod. A lower PRU reflects lower platelet reactivity, whereas a higher PRU reflects higher platelet reactivity.
Time frame: Pre-dose (baseline) up to 24 hours post-dose injection
Population: Full Analysis Set - all participants that were randomized and who had study treatment administered.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Selatogrel 8 mg | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | Baseline (pre-dose) | 156.1 P2Y12 reaction units |
| Selatogrel 8 mg | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 1 hour post-dose | 9.7 P2Y12 reaction units |
| Selatogrel 8 mg | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 2 hours post-dose | 12.4 P2Y12 reaction units |
| Selatogrel 8 mg | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 4 hours post-dose | 30.1 P2Y12 reaction units |
| Selatogrel 8 mg | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 8 hours post-dose | 88.1 P2Y12 reaction units |
| Selatogrel 8 mg | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 24 hours post-dose | 144.2 P2Y12 reaction units |
| Selatogrel 8 mg | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 15 minutes post-dose | 10.1 P2Y12 reaction units |
| Selatogrel 8 mg | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 30 minutes post-dose | 7.9 P2Y12 reaction units |
| Selatogrel 16 mg | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 2 hours post-dose | 5.7 P2Y12 reaction units |
| Selatogrel 16 mg | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 1 hour post-dose | 3.5 P2Y12 reaction units |
| Selatogrel 16 mg | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 4 hours post-dose | 11.4 P2Y12 reaction units |
| Selatogrel 16 mg | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 15 minutes post-dose | 4.5 P2Y12 reaction units |
| Selatogrel 16 mg | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 8 hours post-dose | 47.3 P2Y12 reaction units |
| Selatogrel 16 mg | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 24 hours post-dose | 128.6 P2Y12 reaction units |
| Selatogrel 16 mg | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | Baseline (pre-dose) | 156.2 P2Y12 reaction units |
| Selatogrel 16 mg | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 30 minutes post-dose | 5.3 P2Y12 reaction units |
| Placebo | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 1 hour post-dose | 161.8 P2Y12 reaction units |
| Placebo | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | Baseline (pre-dose) | 155.2 P2Y12 reaction units |
| Placebo | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 2 hours post-dose | 162.0 P2Y12 reaction units |
| Placebo | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 4 hours post-dose | 162.4 P2Y12 reaction units |
| Placebo | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 30 minutes post-dose | 162.2 P2Y12 reaction units |
| Placebo | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 24 hours post-dose | 153.3 P2Y12 reaction units |
| Placebo | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 8 hours post-dose | 164.1 P2Y12 reaction units |
| Placebo | Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points | 15 minutes post-dose | 163.3 P2Y12 reaction units |
Other Pre-specified
Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA)
Light transmission aggregometry was used as complementary method to the VerifyNow® to evaluate the effect of selatogrel on platelet aggregation. Platelet aggregation was triggered by addition of Adenosine diphosphate (ADP) 20 µM (micromole per liter) and monitored over 6 minutes. Maximum Platelet Aggregation (MPA) to 20 μM ADP was assessed by light transmission aggregometry (LTA), an assay that measures platelet aggregation by determining the amount of light transmitted through a cuvette containing platelet-rich plasma stimulated with 20 µM ADP, relative to platelet-poor plasma (100% light transmittance). A lower MPA % reflects stronger platelet inhibition, whereas a higher MPA % reflects weaker inhibition.
Time frame: Pre-dose, and from 30 minutes after administration of the subcutaneous injection up to 8 hours
Population: Full Analysis Set - all participants that were randomized and who had study treatment administered.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selatogrel 8 mg | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) | 8 hours post-dose | 35.4 percent maximum platelet aggregation (%) | Standard Deviation 25.5 |
| Selatogrel 8 mg | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) | 1 hour post-dose | 14.5 percent maximum platelet aggregation (%) | Standard Deviation 14.1 |
| Selatogrel 8 mg | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) | 2 hours post-dose | 17.0 percent maximum platelet aggregation (%) | Standard Deviation 12.8 |
| Selatogrel 8 mg | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) | Pre-dose | 61.9 percent maximum platelet aggregation (%) | Standard Deviation 29.79 |
| Selatogrel 8 mg | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) | 30 minutes post-dose | 13.1 percent maximum platelet aggregation (%) | Standard Deviation 12.1 |
| Selatogrel 16 mg | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) | Pre-dose | 62.4 percent maximum platelet aggregation (%) | Standard Deviation 31.5 |
| Selatogrel 16 mg | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) | 30 minutes post-dose | 13.5 percent maximum platelet aggregation (%) | Standard Deviation 11.9 |
| Selatogrel 16 mg | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) | 2 hours post-dose | 16.5 percent maximum platelet aggregation (%) | Standard Deviation 14.5 |
| Selatogrel 16 mg | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) | 8 hours post-dose | 32.1 percent maximum platelet aggregation (%) | Standard Deviation 25.1 |
| Selatogrel 16 mg | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) | 1 hour post-dose | 15.8 percent maximum platelet aggregation (%) | Standard Deviation 15.7 |
| Placebo | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) | 8 hours post-dose | 63.7 percent maximum platelet aggregation (%) | Standard Deviation 27 |
| Placebo | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) | 1 hour post-dose | 65.6 percent maximum platelet aggregation (%) | Standard Deviation 28 |
| Placebo | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) | 2 hours post-dose | 63.0 percent maximum platelet aggregation (%) | Standard Deviation 26.8 |
| Placebo | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) | 30 minutes post-dose | 65.3 percent maximum platelet aggregation (%) | Standard Deviation 28 |
| Placebo | Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) | Pre-dose | 65.6 percent maximum platelet aggregation (%) | Standard Deviation 29.6 |
Comparison: Longitudinal analysis of the treatment effect, from start of treatment to 8 hours after injection.p-value: <0.000195% CI: [-35.4, -19.6]Mixed Models Analysis
Comparison: Longitudinal analysis of the treatment effect, from start of treatment up to 8 hours after injection.p-value: <0.000195% CI: [-39, -23.1]Mixed Models Analysis
Other Pre-specified
Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation by Site of Treatment Administration (Thigh or Abdomen)
The inhibition of platelet aggregation based on the route of administration, i.e. whether the pharmacodynamic response was different if selatogrel was administered subcutaneously in the thigh or in the abdomen, was analyzed. 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 from 30 minutes after the administration of study treatment and lasting for at least 3 hours was considered a responder.
Time frame: From 15 minutes after administration of the subcutaneous injection up to 24 hours
Population: Full Analysis Set - all participants that were randomized and who had study treatment administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selatogrel 8 mg | Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation by Site of Treatment Administration (Thigh or Abdomen) | 52 Count of participants (i.e., responders) |
| Selatogrel 16 mg | Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation by Site of Treatment Administration (Thigh or Abdomen) | 50 Count of participants (i.e., responders) |
| Placebo | Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation by Site of Treatment Administration (Thigh or Abdomen) | 52 Count of participants (i.e., responders) |
| Selatogrel 16 mg (Abdomen) | Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation by Site of Treatment Administration (Thigh or Abdomen) | 51 Count of participants (i.e., responders) |
| Placebo (Thigh) | Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation by Site of Treatment Administration (Thigh or Abdomen) | 11 Count of participants (i.e., responders) |
| Placebo (Abdomen) | Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation by Site of Treatment Administration (Thigh or Abdomen) | 7 Count of participants (i.e., responders) |
p-value: 0.1915Chi-squared
Other Pre-specified
Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation - Sensitivity Analysis
To assess the robustness of results for the pharmacodynamic response, the main analysis was repeated for the per protocol participants. 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 from 30 minutes after the administration of study treatment and lasting for at least 3 hours was considered a responder.
Time frame: From 15 minutes after administration of the subcutaneous injection up to 24 hours
Population: Per-protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selatogrel 8 mg | Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation - Sensitivity Analysis | 92 Count of participants (i.e., responders) |
| Selatogrel 16 mg | Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation - Sensitivity Analysis | 90 Count of participants (i.e., responders) |
| Placebo | Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation - Sensitivity Analysis | 16 Count of participants (i.e., responders) |
Other Pre-specified
Number of Participants With Bleeding Events
Treatment-emergent adverse events in the category Haemorrhage (excluding laboratory terms) were of special interest and their incidence listed below. The role of the Independent Safety Event Committee was to monitor unblinded safety data obtained in the study, with a specific focus on study-drug-related clinically relevant major bleeding events, occurring within 48 hours after dosing (i.e. the treatment period).
Time frame: From study treatment administration on Day 1 up to 48 hours
Population: The safety analysis set (SAF) included all participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Selatogrel 8 mg | Number of Participants With Bleeding Events | All participants with at least one bleeding event | 11 Participants |
| Selatogrel 8 mg | Number of Participants With Bleeding Events | Eye contusion | 0 Participants |
| Selatogrel 8 mg | Number of Participants With Bleeding Events | Ecchymosis | 0 Participants |
| Selatogrel 8 mg | Number of Participants With Bleeding Events | Petechiae | 0 Participants |
| Selatogrel 8 mg | Number of Participants With Bleeding Events | Vessel puncture site haematoma | 1 Participants |
| Selatogrel 8 mg | Number of Participants With Bleeding Events | Vaginal haemorrhage | 0 Participants |
| Selatogrel 8 mg | Number of Participants With Bleeding Events | Participants with Bleeding event of moderate intensity | 0 Participants |
| Selatogrel 8 mg | Number of Participants With Bleeding Events | Epistaxis | 1 Participants |
| Selatogrel 8 mg | Number of Participants With Bleeding Events | Vessel puncture site bruise | 4 Participants |
| Selatogrel 8 mg | Number of Participants With Bleeding Events | Participants with Bleeding event of mild intensity | 11 Participants |
| Selatogrel 8 mg | Number of Participants With Bleeding Events | Wound haemorrhage | 0 Participants |
| Selatogrel 8 mg | Number of Participants With Bleeding Events | Mouth haemorrhage | 0 Participants |
| Selatogrel 8 mg | Number of Participants With Bleeding Events | Injection site bruising | 3 Participants |
| Selatogrel 8 mg | Number of Participants With Bleeding Events | Participants with Trombolysis In Myocardial Infarction (TIMI) major events | 0 Participants |
| Selatogrel 8 mg | Number of Participants With Bleeding Events | Medical device site bruise | 1 Participants |
| Selatogrel 8 mg | Number of Participants With Bleeding Events | Contusion | 1 Participants |
| Selatogrel 16 mg | Number of Participants With Bleeding Events | Mouth haemorrhage | 1 Participants |
| Selatogrel 16 mg | Number of Participants With Bleeding Events | All participants with at least one bleeding event | 5 Participants |
| Selatogrel 16 mg | Number of Participants With Bleeding Events | Participants with Trombolysis In Myocardial Infarction (TIMI) major events | 0 Participants |
| Selatogrel 16 mg | Number of Participants With Bleeding Events | Participants with Bleeding event of mild intensity | 5 Participants |
| Selatogrel 16 mg | Number of Participants With Bleeding Events | Injection site bruising | 2 Participants |
| Selatogrel 16 mg | Number of Participants With Bleeding Events | Contusion | 1 Participants |
| Selatogrel 16 mg | Number of Participants With Bleeding Events | Ecchymosis | 1 Participants |
| Selatogrel 16 mg | Number of Participants With Bleeding Events | Vessel puncture site bruise | 0 Participants |
| Selatogrel 16 mg | Number of Participants With Bleeding Events | Epistaxis | 0 Participants |
| Selatogrel 16 mg | Number of Participants With Bleeding Events | Petechiae | 0 Participants |
| Selatogrel 16 mg | Number of Participants With Bleeding Events | Vaginal haemorrhage | 0 Participants |
| Selatogrel 16 mg | Number of Participants With Bleeding Events | Wound haemorrhage | 0 Participants |
| Selatogrel 16 mg | Number of Participants With Bleeding Events | Participants with Bleeding event of moderate intensity | 0 Participants |
| Selatogrel 16 mg | Number of Participants With Bleeding Events | Eye contusion | 1 Participants |
| Selatogrel 16 mg | Number of Participants With Bleeding Events | Medical device site bruise | 0 Participants |
| Selatogrel 16 mg | Number of Participants With Bleeding Events | Vessel puncture site haematoma | 0 Participants |
| Placebo | Number of Participants With Bleeding Events | Wound haemorrhage | 1 Participants |
| Placebo | Number of Participants With Bleeding Events | Participants with Trombolysis In Myocardial Infarction (TIMI) major events | 0 Participants |
| Placebo | Number of Participants With Bleeding Events | Contusion | 3 Participants |
| Placebo | Number of Participants With Bleeding Events | All participants with at least one bleeding event | 8 Participants |
| Placebo | Number of Participants With Bleeding Events | Eye contusion | 0 Participants |
| Placebo | Number of Participants With Bleeding Events | Injection site bruising | 0 Participants |
| Placebo | Number of Participants With Bleeding Events | Vaginal haemorrhage | 1 Participants |
| Placebo | Number of Participants With Bleeding Events | Medical device site bruise | 0 Participants |
| Placebo | Number of Participants With Bleeding Events | Vessel puncture site bruise | 3 Participants |
| Placebo | Number of Participants With Bleeding Events | Participants with Bleeding event of mild intensity | 7 Participants |
| Placebo | Number of Participants With Bleeding Events | Epistaxis | 0 Participants |
| Placebo | Number of Participants With Bleeding Events | Vessel puncture site haematoma | 0 Participants |
| Placebo | Number of Participants With Bleeding Events | Petechiae | 1 Participants |
| Placebo | Number of Participants With Bleeding Events | Ecchymosis | 0 Participants |
| Placebo | Number of Participants With Bleeding Events | Mouth haemorrhage | 0 Participants |
| Placebo | Number of Participants With Bleeding Events | Participants with Bleeding event of moderate intensity | 1 Participants |