A Medical Research Study to Evaluate the Effects of ACT-246475 in Adults With Coronary Artery Disease

• Sponsor: Idorsia Pharmaceuticals Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03384966
• Collaborator: (none)
• Enrollment: 346
• Locations: 20
• Arms: 3
• Actual Duration (Months): 7.8
• Patients Per Site: 17.3
• Patients Per Site Per Month: 2.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Stable Coronary Artery Disease	Drug: Selatogrel; Drug: Placebo; Drug: Selatogrel	Phase 2

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 346 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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.
• Primary Purpose: Treatment
• Official Title: A Multi-center, Double-blind, Randomized, Placebo-controlled Study to Assess the Pharmacodynamics, Pharmacokinetics, Tolerability, and Safety of a Single Subcutaneous Injection of ACT-246475 in Adults With Stable Coronary Artery Disease
• Actual Study Start Date: Jan 24, 2018
• Actual Primary Completion Date: Aug 18, 2018
• Actual Study Completion Date: Sep 18, 2018

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: Selatogrel; 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.; Other Names: ACT-246475
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.	Drug: Selatogrel; 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: ACT-246575
Placebo Comparator: Placebo Placebo matching ACT-246475 is supplied in sealed glass vials for reconstitution with water for injection. Placebo will be given as a single subcutaneous dose matching selatogrel to be administered in a volume of 0.8 mL. Administration will performed at the investigational site by qualified personnel.	Drug: Placebo; Matching placebo for subcutaneous administration.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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).

3. 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.

Other Outcome Measures

1. Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation by Site of Treatment Administration (Thigh or Abdomen) [From 15 minutes after administration of the subcutaneous injection up to 24 hours]

   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".

2. Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation - Sensitivity Analysis [From 15 minutes after administration of the subcutaneous injection up to 24 hours]

   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".

3. Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) [Pre-dose, and from 30 minutes after administration of the subcutaneous injection up to 8 hours]

   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.

4. Number of Participants With Bleeding Events [From study treatment administration on Day 1 up to 48 hours]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

5. History of CAD with coronary artery stenosis on coronary angiogram ≥50%.

6. Previously documented myocardial infarction occurring more than 3 months prior to randomization.

7. Antiplatelet background therapy stable for at least 1 month prior to randomization.

8. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida (UF) Jacksonville	Jacksonville	Florida	United States	32209
2	Florida Hospital Tampa - Pepin Heart Institute	Tampa	Florida	United States	33613
3	NorthShore University	Chicago	Illinois	United States	73104
4	Indiana University School of Medicine - Krannert Institute of Cardiology	Indianapolis	Indiana	United States	46202
5	Inova Cardiology	Lutherville	Maryland	United States	21093
6	Mount Sinai Hospital (New York)	New York	New York	United States	10029
7	Inova Center for Thrombosis Research and Translational Medicine	Falls Church	Virginia	United States	22042
8	Institut de Cardiologie de Montréal	Montréal	Quebec	Canada	H1T 1C8
9	Aarhus University Hospital	Aarhus		Denmark	8200
10	Rigshospitalet	Copenhagen		Denmark	2100
11	Universitats-Herzzentrum	Bad Krozingen		Germany	79189
12	University Medical Center Groningen	Groningen		Netherlands	9713 GZ
13	Maastricht UMC	Maastricht		Netherlands	6229 HX
14	St. Antonius Ziekenhuis	Nieuwegein		Netherlands	3435 CM
15	National Heart Centre Singapore	Singapore		Singapore	169609
16	Sahlgrenska University Hospital	Göteborg		Sweden	40530
17	Uppsala University Hospital	Uppsala		Sweden	18288
18	Freeman Hospital - Cardiothoracic Department	Newcastle Upon Tyne		United Kingdom	NE7 7DN
19	Sheffield Teaching Hospitals	Sheffield		United Kingdom	S5 7AU
20	East & North Hertfordshire NHS Trust - Lister Hospital	Stevenage		United Kingdom	SG14AB

Sponsors and Collaborators

• Idorsia Pharmaceuticals Ltd.

Investigators

• Study Director: Clinical Trials, Idorsia Pharmaceuticals Ltd.

Study Documents (Full-Text)

• Study Protocol - Aug 31, 2017
• Statistical Analysis Plan - Oct 16, 2018

More Information

Publications

None provided.

• Responsible Party: Idorsia Pharmaceuticals Ltd.
• ClinicalTrials.gov Identifier: NCT03384966
• Other Study ID Numbers: ID-076A201; 2017-003332-36
• First Posted: Dec 28, 2017
• Last Update Posted: Jun 10, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Idorsia Pharmaceuticals Ltd.: Chronic coronary syndrome
• Additional relevant MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease

Study Results

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 Detail	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.

Arm/Group Title	Selatogrel 8 mg	Selatogrel 16 mg	Placebo
Arm/Group Description	The study had 3 consecutive periods: the screening period, a treatment period and the follow-up period. A participant that met all inclusion criteria and none of the exclusion criteria was randomized. In the treatment period 8 mg of selatogrel (ACT-246475) was administered via a single subcutaneous injection either in the abdomen or the thigh. The follow-up period started on Day 3 and ended with the safety follow-up telephone call or visit (Day 35).	The study had 3 consecutive periods: the screening period, a treatment period and the follow-up period. A participant that met all inclusion criteria and none of the exclusion criteria was randomized. In the treatment period 16 mg of selatogrel (ACT-246475) was administered via a single subcutaneous injection either in the abdomen or the thigh. The follow-up period started on Day 3 and ended with the safety follow-up telephone call or visit (Day 35).	The study had 3 consecutive periods: the screening period, a treatment period and the follow-up period. A participant that met all inclusion criteria and none of the exclusion criteria was randomized. In the treatment period placebo matching selatogrel was administered via a single subcutaneous injection either in the abdomen or the thigh. The follow-up period started on Day 3 and ended with the safety follow-up telephone call or visit (Day 35).
Period Title: Randomized at End of Screening Period
STARTED	115	115	116
COMPLETED	114	115	116
NOT COMPLETED	1	0	0
Period Title: Randomized at End of Screening Period
STARTED	114	115	116
Thigh Administration	57	57	58
Abdomen Administration	57	58	58
Per-protocol Analysis Set	96	90	93
Safety Analysis Set	114	115	116
Pharmacokinetic Analysis Set	111	115	0
COMPLETED	114	115	116
NOT COMPLETED	0	0	0
Period Title: Randomized at End of Screening Period
STARTED	114	115	116
COMPLETED	113	115	116
NOT COMPLETED	1	0	0

Baseline Characteristics

Arm/Group Title	Selatogrel 8 mg	Selatogrel 16 mg	Placebo	Total
Arm/Group Description	Selatogrel (ACT-246475) 8 mg was administered as a single subcutaneous dose.	Selatogrel (ACT-246475) 16 mg was administered as a single subcutaneous dose.	Matching placebo was administered as a single subcutaneous dose.	Total of all reporting groups
Overall Participants	114	115	116	345
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	48 42.1%	48 41.7%	55 47.4%	151 43.8%
>=65 years	66 57.9%	67 58.3%	61 52.6%	194 56.2%
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	41 36%	36 31.3%	43 37.1%	120 34.8%
>=65 years	55 48.2%	54 47%	50 43.1%	159 46.1%
Age (years) [Mean (Standard Deviation) ]
Full analysis set	64.8 (9.4)	65.2 (8.5)	64.9 (9.1)	65.0 (9.0)
Per-protocol analysis set	64.4 (9.7)	65.3 (8.8)	65.1 (9.2)	64.9 (9.2)
Sex: Female, Male (Count of Participants)
Female	20 17.5%	26 22.6%	23 19.8%	69 20%
Male	94 82.5%	89 77.4%	93 80.2%	276 80%
Female	16 14%	17 14.8%	16 13.8%	49 14.2%
Male	80 70.2%	73 63.5%	77 66.4%	230 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 0.9%	1 0.9%	0 0%	2 0.6%
Not Hispanic or Latino	113 99.1%	114 99.1%	116 100%	343 99.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Hispanic or Latino	1 0.9%	1 0.9%	0 0%	2 0.6%
Not Hispanic or Latino	95 83.3%	89 77.4%	93 80.2%	277 80.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	7 6.1%	6 5.2%	4 3.4%	17 4.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	10 8.8%	13 11.3%	9 7.8%	32 9.3%
White	97 85.1%	96 83.5%	103 88.8%	296 85.8%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	7 6.1%	5 4.3%	4 3.4%	16 4.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	8 7%	6 5.2%	7 6%	21 6.1%
White	81 71.1%	79 68.7%	82 70.7%	242 70.1%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Canada	1 0.9%	1 0.9%	4 3.4%	6 1.7%
Sweden	7 6.1%	13 11.3%	10 8.6%	30 8.7%
Netherlands	25 21.9%	19 16.5%	21 18.1%	65 18.8%
Singapore	4 3.5%	2 1.7%	2 1.7%	8 2.3%
United States	52 45.6%	50 43.5%	51 44%	153 44.3%
Denmark	0 0%	1 0.9%	0 0%	1 0.3%
United Kingdom	22 19.3%	28 24.3%	27 23.3%	77 22.3%
Germany	3 2.6%	1 0.9%	1 0.9%	5 1.4%
Body Mass Index (kilograms per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Full analysis set	29 (5)	29 (6)	31 (5)	30 (5)
Per-protocol analysis set	29 (5)	29 (5)	30 (5)	29 (5)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set - all participants that were randomized and who had study treatment administered.

Arm/Group Title	Selatogrel 8 mg	Selatogrel 16 mg	Placebo
Arm/Group Description	Selatogrel 8 mg was administered as a single subcutaneous dose.	Selatogrel 16 mg was administered as a single subcutaneous dose.	Matching placebo was administered as a single subcutaneous dose.
Measure Participants	114	115	116
Number [Count of participants (i.e., responders)]	102 89.5%	103 89.6%	18 15.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Selatogrel 8 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	A p-value significance level was set to 0.025, based on an overall Type-I error rate of 0.05 adjusted for multiple comparisons using a Bonferroni approach (two comparisons).
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	58.9
	Confidence Interval	(2-Sided) 97.5%; 22.4 to 154.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Selatogrel 16 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	A p-value significance level was set to 0.025, based on an overall Type-I error rate of 0.05 adjusted for multiple comparisons using a Bonferroni approach (two comparisons).
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	61.2
	Confidence Interval	(2-Sided) 97.5%; 23.1 to 162.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Maximum Selatogrel Plasma Concentration (Cmax)
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis set - all participants that had a selatogrel concentration measurement after administration of study treatment.

Arm/Group Title	Selatogrel 8 mg	Selatogrel 16 mg
Arm/Group Description	Selatogrel 8 mg was administered as a single subcutaneous dose.	Selatogrel 16 mg was administered as a single subcutaneous dose.
Measure Participants	111	115
Geometric Mean (Full Range) [ng/mL]	298	484

3. Secondary Outcome

Title	Time to Reach Maximum Selatogrel Plasma Concentration (Tmax)
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis set - all participants that had a selatogrel concentration measurement after administration of study treatment.

Arm/Group Title	Selatogrel 8 mg	Selatogrel 16 mg
Arm/Group Description	Selatogrel 8 mg was administered as a single subcutaneous dose.	Selatogrel 16 mg was administered as a single subcutaneous dose.
Measure Participants	111	115
Median (Full Range) [hour]	0.52	0.53

4. Secondary Outcome

Title	Area Under the Plasma Concentration-time Curve of Selatogrel From Time Zero to 24 Hour Time Point (AUC0-24)
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis set - all participants that had a selatogrel concentration measurement after administration of study treatment.

Arm/Group Title	Selatogrel 8 mg	Selatogrel 16 mg
Arm/Group Description	Selatogrel 8 mg was administered as a single subcutaneous dose.	Selatogrel 16 mg was administered as a single subcutaneous dose.
Measure Participants	111	115
Geometric Mean (Full Range) [hours*ng/mL]	716	1358

5. Other Pre-specified Outcome

Title	Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation by Site of Treatment Administration (Thigh or Abdomen)
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set - all participants that were randomized and who had study treatment administered.

Arm/Group Title	Selatogrel 8 mg (Thigh)	Selatogrel 8 mg (Abdomen)	Selatogrel 16 mg (Thigh)	Selatogrel 16 mg (Abdomen)	Placebo (Thigh)	Placebo (Abdomen)
Arm/Group Description	Selatogrel 8 mg was administered as a single subcutaneous dose.	Selatogrel 8 mg was administered as a single subcutaneous dose.	Selatogrel 16 mg was administered as a single subcutaneous dose.	Selatogrel 16 mg was administered as a single subcutaneous dose.	Matching placebo was administered as a single subcutaneous dose.	Matching placebo was administered as a single subcutaneous dose.
Measure Participants	57	57	57	58	58	58
Number [Count of participants (i.e., responders)]	52 45.6%	50 43.5%	52 44.8%	51 14.8%	11 NaN	7 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Selatogrel 8 mg, Selatogrel 16 mg, Placebo, Selatogrel 16 mg (Abdomen)
	Comments
	Type of Statistical Test	Other
	Comments	Logistic regression (Type III analysis)
Statistical Test of Hypothesis	p-Value	0.1915
	Comments
	Method	Chi-squared
	Comments

6. Other Pre-specified Outcome

Title	Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation - Sensitivity Analysis
Description	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

Outcome Measure Data

Analysis Population Description

Per-protocol set

Arm/Group Title	Selatogrel 8 mg	Selatogrel 16 mg	Placebo
Arm/Group Description	Selatogrel 8 mg was administered as a single subcutaneous dose.	Selatogrel 16 mg was administered as a single subcutaneous dose.	Matching placebo was administered as a single subcutaneous dose.
Measure Participants	96	90	93
Number [Count of participants (i.e., responders)]	92 80.7%	90 78.3%	16 13.8%

7. Other Pre-specified Outcome

Title	Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA)
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set - all participants that were randomized and who had study treatment administered.

Arm/Group Title	Selatogrel 8 mg	Selatogrel 16 mg	Placebo
Arm/Group Description	Selatogrel 8 mg was administered as a single subcutaneous dose.	Selatogrel 16 mg was administered as a single subcutaneous dose.	Matching placebo was administered as a single subcutaneous dose.
Measure Participants	114	115	116
Pre-dose	61.9 (29.79)	62.4 (31.5)	65.6 (29.6)
30 minutes post-dose	13.1 (12.1)	13.5 (11.9)	65.3 (28.0)
1 hour post-dose	14.5 (14.1)	15.8 (15.7)	65.6 (28.0)
2 hours post-dose	17.0 (12.8)	16.5 (14.5)	63.0 (26.8)
8 hours post-dose	35.4 (25.5)	32.1 (25.1)	63.7 (27.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Selatogrel 8 mg, Placebo
	Comments	Longitudinal analysis of the treatment effect, from start of treatment to 8 hours after injection.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Mixed Models Analysis
	Comments	P-value significance level is set to 0.025, i.e. type I error (0.05) adjusted for multiplicity (2 comparisons) using a Bonferroni approach.
Method of Estimation	Estimation Parameter	LS Mean difference with placebo
	Estimated Value	-27.49
	Confidence Interval	(2-Sided) 95%; -35.4 to -19.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Selatogrel 16 mg, Placebo
	Comments	Longitudinal analysis of the treatment effect, from start of treatment up to 8 hours after injection.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Mixed Models Analysis
	Comments	P-value significance level is set to 0.025, i.e. type I error (0.05) adjusted for multiplicity (2 comparisons) using a Bonferroni approach
Method of Estimation	Estimation Parameter	LS Mean difference with placebo
	Estimated Value	-31.06
	Confidence Interval	(2-Sided) 95%; -39.0 to -23.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Other Pre-specified Outcome

Title	Number of Participants With Bleeding Events
Description	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

Outcome Measure Data

Analysis Population Description

The safety analysis set (SAF) included all participants who received at least one dose of study medication.

Arm/Group Title	Selatogrel 8 mg	Selatogrel 16 mg	Placebo
Arm/Group Description	Selatogrel 8 mg was administered as a single subcutaneous dose.	Selatogrel 16 mg was administered as a single subcutaneous dose.	Matching placebo was administered as a single subcutaneous dose.
Measure Participants	114	115	116
All participants with at least one "bleeding event"	11 9.6%	5 4.3%	8 6.9%
Participants with Trombolysis In Myocardial Infarction (TIMI) major events	0 0%	0 0%	0 0%
Participants with "Bleeding event of moderate intensity"	0 0%	0 0%	1 0.9%
Participants with "Bleeding event of mild intensity"	11 9.6%	5 4.3%	7 6%
Injection site bruising	3 2.6%	2 1.7%	0 0%
Contusion	1 0.9%	1 0.9%	3 2.6%
Ecchymosis	0 0%	1 0.9%	0 0%
Eye contusion	0 0%	1 0.9%	0 0%
Medical device site bruise	1 0.9%	0 0%	0 0%
Mouth haemorrhage	0 0%	1 0.9%	0 0%
Vessel puncture site bruise	4 3.5%	0 0%	3 2.6%
Epistaxis	1 0.9%	0 0%	0 0%
Vessel puncture site haematoma	1 0.9%	0 0%	0 0%
Petechiae	0 0%	0 0%	1 0.9%
Vaginal haemorrhage	0 0%	0 0%	1 0.9%
Wound haemorrhage	0 0%	0 0%	1 0.9%

9. Post-Hoc Outcome

Title	Assessments of the Inhibition of Platelet Reactivity at Predefined Time Points
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set - all participants that were randomized and who had study treatment administered.

Arm/Group Title	Selatogrel 8 mg	Selatogrel 16 mg	Placebo
Arm/Group Description	Selatogrel 8 mg was administered as a single subcutaneous dose.	Selatogrel 16 mg was administered as a single subcutaneous dose.	Matching placebo was administered as a single subcutaneous dose.
Measure Participants	114	115	116
Baseline (pre-dose)	156.1	156.2	155.2
15 minutes post-dose	10.1	4.5	163.3
30 minutes post-dose	7.9	5.3	162.2
1 hour post-dose	9.7	3.5	161.8
2 hours post-dose	12.4	5.7	162.0
4 hours post-dose	30.1	11.4	162.4
8 hours post-dose	88.1	47.3	164.1
24 hours post-dose	144.2	128.6	153.3

Adverse Events

Time Frame	Adverse events were recorded up to 35 days after the single subcutaneous selatogrel dose administration. Treatment period: Treatment emergent adverse events were those adverse events with onset and up to 48 hours after study treatment administration. The follow-up period started on Day 3 and ended with the safety follow-up telephone call 35 days after selatogrel administration. During the follow-up period the participants continued to be observed. No interventions were performed.
Arm/Group Title	Treatment Period - Selatogrel 8 mg		Treatment Period - Selatogrel 16 mg		Treatment Period - Placebo		Follow-up Period - Selatogrel 8 mg		Follow-up Period - Selatogrel 16 mg		Follow-up Period - Placebo
Arm/Group Description	In the treatment period 8 mg of selatogrel was administered via a single subcutaneous injection either in the abdomen or the thigh.		In the treatment period 16 mg of selatogrel was administered via a single subcutaneous injection either in the abdomen or the thigh.		In the treatment period placebo matching selatogrel was administered via a single subcutaneous injection either in the abdomen or the thigh.		Participants that had been administered a single subcutaneous injection containing 8 mg selatogrel in the treatment period were followed-up for adverse events after the treatment period. The follow-up period started on Day 3 and ended with a telephone call or visit on Day 35.		Participants that had been administered a single subcutaneous injection containing 16 mg selatogrel were followed-up for adverse events after the treatment period. The follow-up period started on Day 3 and ended with a telephone call or visit on Day 35.		Participants that had been administered a single subcutaneous injection containing placebo matching selatogrel were followed-up for adverse events after the treatment period. The follow-up period started on Day 3 and ended with a telephone call or visit on Day 35.
All Cause Mortality
	Treatment Period - Selatogrel 8 mg		Treatment Period - Selatogrel 16 mg		Treatment Period - Placebo		Follow-up Period - Selatogrel 8 mg		Follow-up Period - Selatogrel 16 mg		Follow-up Period - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/114 (0%)		0/115 (0%)		0/116 (0%)		1/114 (0.9%)		0/115 (0%)		0/116 (0%)
Serious Adverse Events
	Treatment Period - Selatogrel 8 mg		Treatment Period - Selatogrel 16 mg		Treatment Period - Placebo		Follow-up Period - Selatogrel 8 mg		Follow-up Period - Selatogrel 16 mg		Follow-up Period - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/114 (0%)		0/115 (0%)		0/116 (0%)		5/114 (4.4%)		1/115 (0.9%)		1/116 (0.9%)
Cardiac disorders
Atrial fibrillation	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0
Angina pectoris	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0
Myocardial infarctions	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1
Cardiac arrest	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0
Ventricular fibrillation	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0
General disorders
Non-cardiac chest pain	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0
Musculoskeletal and connective tissue disorders
Costochondritis	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0
Nervous system disorders
Syncope	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	1/114 (0.9%)	2	0/115 (0%)	0	0/116 (0%)	0
Other (Not Including Serious) Adverse Events
	Treatment Period - Selatogrel 8 mg		Treatment Period - Selatogrel 16 mg		Treatment Period - Placebo		Follow-up Period - Selatogrel 8 mg		Follow-up Period - Selatogrel 16 mg		Follow-up Period - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/114 (31.6%)		26/115 (22.6%)		25/116 (21.6%)		13/114 (11.4%)		10/115 (8.7%)		13/116 (11.2%)
Cardiac disorders
Cardiac failure	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Ear and labyrinth disorders
Vertigo	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Diarrhoea	4/114 (3.5%)	4	1/115 (0.9%)	1	0/116 (0%)	0	0/114 (0%)	0	2/115 (1.7%)	2	1/116 (0.9%)	1
Flatulence	1/114 (0.9%)	1	0/115 (0%)	0	1/116 (0.9%)	1	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Mouth haemorrhage	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Nausea	0/114 (0%)	0	1/115 (0.9%)	1	1/116 (0.9%)	1	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1
Vomiting	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Constipation	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0
Gastric haemorrhage	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0
Dyspepsia	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1
General disorders
Injection site bruise	3/114 (2.6%)	3	2/115 (1.7%)	2	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Injection site erythema	0/114 (0%)	0	2/115 (1.7%)	2	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Injection site pruritus	0/114 (0%)	0	2/115 (1.7%)	2	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Injection site reaction	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Medical device site bruising	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Oedema peripheral	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0
Peripheral swelling	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1
Pyrexia	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Vessel puncture site bruise	4/114 (3.5%)	6	0/115 (0%)	0	3/116 (2.6%)	4	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Vessel puncture site erythema	2/114 (1.8%)	2	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Vessel puncture site haematoma	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Non-cardiac chest pain	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0
Malaise	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	1/114 (0.9%)	1	0/115 (0%)	0	1/116 (0.9%)	1
Fatigue	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0
Infections and infestations
Herpes zoster	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0
Nasopharyngitis	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0
Lower respiratory tract infection	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1
Urinary tract infection	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1
Injury, poisoning and procedural complications
Contusion	1/114 (0.9%)	1	1/115 (0.9%)	1	3/116 (2.6%)	3	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0
Eye contusion	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Procedural dizziness	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Procedural nausea	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Wound haemorrhage	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Chemical burns of eye	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0
Back injury	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1
Road traffic accident	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1
Investigations
Blood creatinine increased	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Blood potassium increased	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
White blood cell count increased	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
ECG P wave inverted	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Iron deficiency	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1
Metabolism and nutrition disorders
Gout	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Hypoglycaemia	1/114 (0.9%)	1	1/115 (0.9%)	1	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Hypercholesterolaemia	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0
Blood glucose increased	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle spasms	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Musculoskeletal discomfort	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Arthralgia	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0
Myalgia	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0
Joint swelling	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1
Rheumatoid arthritis	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1
Nervous system disorders
Dizziness	5/114 (4.4%)	5	4/115 (3.5%)	4	1/116 (0.9%)	1	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0
Headache	3/114 (2.6%)	3	3/115 (2.6%)	3	5/116 (4.3%)	5	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Dizziness postural	1/114 (0.9%)	1	0/115 (0%)	0	1/116 (0.9%)	1	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Lethargy	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Presyncope	2/114 (1.8%)	2	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Dysgeusia	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0
Pain in extremity	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	1/114 (0.9%)	1	0/115 (0%)	0	1/116 (0.9%)	1
Neuralgia	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1
Psychiatric disorders
Insomnia	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Anxiety	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0
Renal and urinary disorders
Pollakiuria	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Renal impairment	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Renal pain	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0
Reproductive system and breast disorders
Vaginal haemorrhage	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1
Chronic obstructive pulmonary disease	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0
Oropharyngeal pain	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0
Dyspnoea	6/114 (5.3%)	6	10/115 (8.7%)	10	0/116 (0%)	0	1/114 (0.9%)	1	0/115 (0%)	0	0/116 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis contact	1/114 (0.9%)	1	0/115 (0%)	0	1/116 (0.9%)	1	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Ecchymosis	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Erythema	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Hyperhidrosis	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Petechiae	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Actinic keratosis	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	1/116 (0.9%)	1
Vascular disorders
Hypertension	0/114 (0%)	0	1/115 (0.9%)	1	2/116 (1.7%)	2	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0
Hypotension	0/114 (0%)	0	1/115 (0.9%)	1	0/116 (0%)	0	0/114 (0%)	0	0/115 (0%)	0	0/116 (0%)	0

Limitations/Caveats

Blood was collected with phenylalanine-proline-arginine-chloromethyl ketone as anticoagulant. Any direct comparison of absolute PRU values obtained in this study with those published from studies of other P2Y12 inhibitors should take this into account.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.