Trial Outcomes & Findings for A Study Evaluating the Safety, Tolerability, and Effect on Microvascular Obstruction of Intravenous Temanogrel in Adult Participants Undergoing Percutaneous Coronary Intervention (NCT NCT04848220)

Results Overview

IMR was defined as the mean distal pressure at maximum hyperemia multiplied by the mean hyperemic transit time. IMRcorr (IMR corrected for the influence from collateral supply) was calculated using the following equation, to account for the presence of significant epicardial stenosis without the need for balloon dilation to measure the coronary wedge pressure (Pw), IMRcorr = mean aortic pressure at maximum hyperemia (Pa)\*mean transit time at maximal hyperemia (Tmn) \* \[1.34 \* mean distal coronary pressure at maximum hyperemia (Pd)/Pa minus 0.32\].

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

29 participants

Primary outcome timeframe

From Baseline (prior to administration of study treatment) to 15 minutes post-PCI on Day 1

Results posted on

2023-12-12

Participant Flow

This study was conducted in two stages: Stage A (an ascending single dose study consisting of 2 cohorts of 20 and 40 milligram \[mg\] doses of temanogrel or placebo) and Stage B: parallel group study (consisting of 3 treatment groups of temanogrel 20 mg, temanogrel 40 mg and placebo). The study was terminated early due to business decision. Analysis of stage A and B was combined as pre specified in the protocol.

A total of 29 participants were enrolled and randomized in the study.

Participant milestones

Participant milestones
Measure	Temanogrel 20 mg Participants received a single intravenous (IV) dose of temanogrel 20 mg on Day 1 following which the participants underwent percutaneous coronary intervention (PCI). Participants had a follow-up phone call 7 days after administration of study treatment.	Temanogrel 40 mg Participants received a single IV dose of temanogrel 40mg on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Placebo Participants received a single IV dose of placebo on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.
Overall Study STARTED	10	10	9
Overall Study Treated	10	8	9
Overall Study COMPLETED	10	8	9
Overall Study NOT COMPLETED	0	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Temanogrel 20 mg Participants received a single intravenous (IV) dose of temanogrel 20 mg on Day 1 following which the participants underwent percutaneous coronary intervention (PCI). Participants had a follow-up phone call 7 days after administration of study treatment.	Temanogrel 40 mg Participants received a single IV dose of temanogrel 40mg on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Placebo Participants received a single IV dose of placebo on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.
Overall Study Unable to proceed to study procedure	0	1	0
Overall Study Fractional flow not significant	0	1	0

Baseline Characteristics

A Study Evaluating the Safety, Tolerability, and Effect on Microvascular Obstruction of Intravenous Temanogrel in Adult Participants Undergoing Percutaneous Coronary Intervention

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Temanogrel 20 mg n=10 Participants Participants received a single intravenous (IV) dose of temanogrel 20 mg on Day 1 following which the participants underwent percutaneous coronary intervention (PCI). Participants had a follow-up phone call 7 days after administration of study treatment.	Temanogrel 40 mg n=10 Participants Participants received a single IV dose of temanogrel 40mg on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Placebo n=9 Participants Participants received a single IV dose of placebo on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Total n=29 Participants Total of all reporting groups
Age, Continuous	65.9 Years STANDARD_DEVIATION 7.81 • n=5 Participants	64.5 Years STANDARD_DEVIATION 3.27 • n=7 Participants	63.3 Years STANDARD_DEVIATION 9.63 • n=5 Participants	64.6 Years STANDARD_DEVIATION 7.12 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	10 Participants n=7 Participants	6 Participants n=5 Participants	25 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	9 Participants n=7 Participants	9 Participants n=5 Participants	28 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	8 Participants n=7 Participants	9 Participants n=5 Participants	24 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: From Baseline (prior to administration of study treatment) to 15 minutes post-PCI on Day 1

Population: FAS included all randomized participants, irrespective of whether they received any study treatment. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure. Combined data for Stage A and Stage B is presented as pre-specified in protocol.

IMR was defined as the mean distal pressure at maximum hyperemia multiplied by the mean hyperemic transit time. IMRcorr (IMR corrected for the influence from collateral supply) was calculated using the following equation, to account for the presence of significant epicardial stenosis without the need for balloon dilation to measure the coronary wedge pressure (Pw), IMRcorr = mean aortic pressure at maximum hyperemia (Pa)\*mean transit time at maximal hyperemia (Tmn) \* \[1.34 \* mean distal coronary pressure at maximum hyperemia (Pd)/Pa minus 0.32\].

Outcome measures

Outcome measures
Measure	Temanogrel 20 mg n=9 Participants Participants received a single intravenous (IV) dose of temanogrel 20 mg on Day 1 following which the participants underwent percutaneous coronary intervention (PCI). Participants had a follow-up phone call 7 days after administration of study treatment.	Temanogrel 40 mg n=8 Participants Participants received a single IV dose of temanogrel 40mg on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Placebo n=9 Participants Participants received a single IV dose of placebo on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.
Change in Index of Microcirculatory Resistance (IMR) From Baseline to Post Percutaneous Coronary Intervention (PCI)	-8.1783 Millimeter of mercury*seconds Standard Deviation 15.35531	0.0691 Millimeter of mercury*seconds Standard Deviation 13.27702	-1.8907 Millimeter of mercury*seconds Standard Deviation 18.82659

SECONDARY outcome

Timeframe: From Baseline (prior to administration of study treatment) to 15 minutes post-PCI on Day 1

Population: FAS included all randomized participants, irrespective of whether they received any study treatment. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure. Combined data for Stage A and Stage B is presented as pre-specified in protocol.

The coronary flow reserve (CFR) was calculated from the ratio of baseline (i.e., resting transit time) to hyperemic mean transit time.

Outcome measures

Outcome measures
Measure	Temanogrel 20 mg n=9 Participants Participants received a single intravenous (IV) dose of temanogrel 20 mg on Day 1 following which the participants underwent percutaneous coronary intervention (PCI). Participants had a follow-up phone call 7 days after administration of study treatment.	Temanogrel 40 mg n=8 Participants Participants received a single IV dose of temanogrel 40mg on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Placebo n=9 Participants Participants received a single IV dose of placebo on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.
Change From Baseline to Post-PCI for Coronary Flow Reserve (CFR)	1.2744 Ratio Standard Deviation 0.89307	1.0238 Ratio Standard Deviation 2.97729	1.3787 Ratio Standard Deviation 1.40440

SECONDARY outcome

Timeframe: From Baseline (prior to administration of study treatment) to 15 minutes post-PCI on Day 1

Population: FAS included all randomized participants, irrespective of whether they received any study treatment. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure. Combined data for Stage A and Stage B is presented as pre-specified in protocol.

The FFR was calculated from the ratio of distal to proximal mean pressures at maximal hyperemia (FFR = \[distal coronary pressure/aortic pressure at maximum hyperemia\]).

Outcome measures

Outcome measures
Measure	Temanogrel 20 mg n=9 Participants Participants received a single intravenous (IV) dose of temanogrel 20 mg on Day 1 following which the participants underwent percutaneous coronary intervention (PCI). Participants had a follow-up phone call 7 days after administration of study treatment.	Temanogrel 40 mg n=8 Participants Participants received a single IV dose of temanogrel 40mg on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Placebo n=9 Participants Participants received a single IV dose of placebo on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.
Change From Baseline to Post-PCI for Fractional Flow Reserve (FFR)	0.1346 Ratio Standard Deviation 0.19620	0.2494 Ratio Standard Deviation 0.20758	0.3123 Ratio Standard Deviation 0.16562

SECONDARY outcome

Timeframe: From Baseline (prior to administration of study treatment) to 15 minutes post-PCI on Day 1

Population: Safety set included all participants in the FAS who received any study treatment. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure. Combined data for Stage A and Stage B is presented as pre-specified in protocol.

The cTFC is a quantitative index of coronary flow and was calculated based upon the number of cine-frames that the intracoronary dye required to reach distal coronary landmarks.

Outcome measures

Outcome measures
Measure	Temanogrel 20 mg n=9 Participants Participants received a single intravenous (IV) dose of temanogrel 20 mg on Day 1 following which the participants underwent percutaneous coronary intervention (PCI). Participants had a follow-up phone call 7 days after administration of study treatment.	Temanogrel 40 mg n=7 Participants Participants received a single IV dose of temanogrel 40mg on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Placebo n=8 Participants Participants received a single IV dose of placebo on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.
Change From Baseline to Post-PCI for Corrected Thrombolysis in Myocardial Infarction Frame Count (cTFC)	-6.54 Frames per second Standard Deviation 7.365	-0.81 Frames per second Standard Deviation 6.320	-8.93 Frames per second Standard Deviation 8.368

SECONDARY outcome

Timeframe: Baseline (prior to administration of study treatment) and anytime between 0 to 15 minutes post-PCI on Day 1

Population: Safety set included all participants in the FAS who received any study treatment. Combined data for Stage A and Stage B is presented as pre-specified in protocol.

The TFG is a measure of epicardial perfusion and was graded on a standard scale from 0 to 3, where Grade 0=no perfusion, grade 1=penetration without perfusion, grade 2=partial perfusion and grade 3= complete perfusion.

Outcome measures

Outcome measures
Measure	Temanogrel 20 mg n=10 Participants Participants received a single intravenous (IV) dose of temanogrel 20 mg on Day 1 following which the participants underwent percutaneous coronary intervention (PCI). Participants had a follow-up phone call 7 days after administration of study treatment.	Temanogrel 40 mg n=8 Participants Participants received a single IV dose of temanogrel 40mg on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Placebo n=9 Participants Participants received a single IV dose of placebo on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.
Number of Participants According to Change From Baseline to Post-PCI for Thrombolysis in Myocardial Infarction (TIMI) Flow Grade (TFG) Post-PCI Baseline Grade 3	10 Participants	8 Participants	9 Participants
Number of Participants According to Change From Baseline to Post-PCI for Thrombolysis in Myocardial Infarction (TIMI) Flow Grade (TFG) Post-PCI 0 to 15 min post-PCI Grade 3	9 Participants	8 Participants	8 Participants
Number of Participants According to Change From Baseline to Post-PCI for Thrombolysis in Myocardial Infarction (TIMI) Flow Grade (TFG) Post-PCI 0 to 15 min post-PCI missing	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline (prior to administration of study treatment) and anytime between 0 to 15 minutes post-PCI on Day 1

Population: Safety set included all participants in the FAS who received any study treatment. Combined data for Stage A and Stage B is presented as pre-specified in protocol.

The TMPG (also known as myocardial blush grade \[MBG\]), is a measure of myocardial perfusion in the capillary bed at the tissues level following contrast injection into the coronary artery. TMPG was graded on a scale from 0 to 3, where grade 0 = failure of dye to enter the microvasculature; grade 1 = dye slowly enters but fails to exit the microvasculature; grade 2 = delayed entry and exit of dye from the microvasculature; grade 3= normal entry and exit of dye from the microvasculature.

Outcome measures

Outcome measures
Measure	Temanogrel 20 mg n=10 Participants Participants received a single intravenous (IV) dose of temanogrel 20 mg on Day 1 following which the participants underwent percutaneous coronary intervention (PCI). Participants had a follow-up phone call 7 days after administration of study treatment.	Temanogrel 40 mg n=8 Participants Participants received a single IV dose of temanogrel 40mg on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Placebo n=9 Participants Participants received a single IV dose of placebo on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.
Number of Participants According to Change From Baseline to Post-PCI in Thrombolysis in Myocardial Infarction Myocardial Perfusion Grade (TMPG) Post-PCI Baseline TMPG value 2	1 Participants	0 Participants	1 Participants
Number of Participants According to Change From Baseline to Post-PCI in Thrombolysis in Myocardial Infarction Myocardial Perfusion Grade (TMPG) Post-PCI Baseline TMPG value 3	7 Participants	4 Participants	3 Participants
Number of Participants According to Change From Baseline to Post-PCI in Thrombolysis in Myocardial Infarction Myocardial Perfusion Grade (TMPG) Post-PCI Baseline Missing	2 Participants	4 Participants	5 Participants
Number of Participants According to Change From Baseline to Post-PCI in Thrombolysis in Myocardial Infarction Myocardial Perfusion Grade (TMPG) Post-PCI 0 to 15 min post-PCI TMPG value 3	9 Participants	6 Participants	6 Participants
Number of Participants According to Change From Baseline to Post-PCI in Thrombolysis in Myocardial Infarction Myocardial Perfusion Grade (TMPG) Post-PCI 0 to 15 min post-PCI Missing	1 Participants	2 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline (prior to administration of study treatment), anytime between 0 to 15 minutes, 6 hours post-PCI, and 24 hours post-PCI/discharge

Population: Safety Set included all participants in the FAS who received any study treatment. Here, 'Number Analyzed' signifies number of participants evaluable at the specified timepoints. Combined data for Stage A and Stage B is presented as pre-specified in protocol.

Outcome measures

Outcome measures
Measure	Temanogrel 20 mg n=10 Participants Participants received a single intravenous (IV) dose of temanogrel 20 mg on Day 1 following which the participants underwent percutaneous coronary intervention (PCI). Participants had a follow-up phone call 7 days after administration of study treatment.	Temanogrel 40 mg n=8 Participants Participants received a single IV dose of temanogrel 40mg on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Placebo n=9 Participants Participants received a single IV dose of placebo on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.
Change From Baseline to Post-PCI for Creatine Kinase (CK) 0 to 15 minutes post-PCI	-11.7 Units per liter Standard Deviation 11.25	-6.0 Units per liter Standard Deviation 5.68	-5.9 Units per liter Standard Deviation 10.58
Change From Baseline to Post-PCI for Creatine Kinase (CK) 6 hours post-PCI	0.9 Units per liter Standard Deviation 17.20	1.5 Units per liter Standard Deviation 27.07	-23.5 Units per liter Standard Deviation 41.03
Change From Baseline to Post-PCI for Creatine Kinase (CK) 24 hours post- PCI/discharge	-33.7 Units per liter Standard Deviation 23.42	233.0 Units per liter Standard Deviation NA Standard deviation could not be calculated for only one participant.	-6.0 Units per liter Standard Deviation 38.94

SECONDARY outcome

Timeframe: Baseline (prior to administration of study treatment), anytime between 0 to 15 minutes, 6 hours post-PCI and 24 hours post-PCI/discharge

Population: Safety Set included all participants in the FAS who received any study treatment. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here, 'Number Analyzed' signifies number of participants evaluable at the specified timepoints. Combined data for Stage A and Stage B is presented as pre-specified in protocol.

Outcome measures

Outcome measures
Measure	Temanogrel 20 mg n=10 Participants Participants received a single intravenous (IV) dose of temanogrel 20 mg on Day 1 following which the participants underwent percutaneous coronary intervention (PCI). Participants had a follow-up phone call 7 days after administration of study treatment.	Temanogrel 40 mg n=8 Participants Participants received a single IV dose of temanogrel 40mg on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Placebo n=9 Participants Participants received a single IV dose of placebo on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.
Change From Baseline to Post-PCI for Creatine Kinase-Myocardial Band (CK-MB) 0 to 15 minutes Post-PCI	-0.18 Micrograms per liter Standard Deviation 0.290	-0.18 Micrograms per liter Standard Deviation 0.225	-0.26 Micrograms per liter Standard Deviation 0.490
Change From Baseline to Post-PCI for Creatine Kinase-Myocardial Band (CK-MB) 6 Hours Post-PCI	0.70 Micrograms per liter Standard Deviation 1.260	0.79 Micrograms per liter Standard Deviation 2.208	-0.63 Micrograms per liter Standard Deviation 1.359
Change From Baseline to Post-PCI for Creatine Kinase-Myocardial Band (CK-MB) 24 Hours Post- PCI/Discharge	-0.05 Micrograms per liter Standard Deviation 0.804	31.80 Micrograms per liter Standard Deviation NA Standard deviation could not be calculated for only one participant.	0.97 Micrograms per liter Standard Deviation 0.643

SECONDARY outcome

Timeframe: Baseline (prior to administration of study treatment), anytime between 0 to 15 minutes, 6 hours post-PCI and 24 hours post-PCI/discharge

Population: Safety Set included all participants in the FAS who received any study treatment. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here, 'Number Analyzed' signifies number of participants evaluable at the specified timepoints. Combined data for Stage A and Stage B is presented as pre-specified in protocol.

Outcome measures

Outcome measures
Measure	Temanogrel 20 mg n=10 Participants Participants received a single intravenous (IV) dose of temanogrel 20 mg on Day 1 following which the participants underwent percutaneous coronary intervention (PCI). Participants had a follow-up phone call 7 days after administration of study treatment.	Temanogrel 40 mg n=8 Participants Participants received a single IV dose of temanogrel 40mg on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Placebo n=9 Participants Participants received a single IV dose of placebo on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.
Change From Baseline to Post-PCI for Cardiac Troponin I 0 to 15 minutes Post-PCI	-0.04 Microgram per liter Standard Deviation 0.126	0.01 Microgram per liter Standard Deviation 0.035	0.04 Microgram per liter Standard Deviation 0.052
Change From Baseline to Post-PCI for Cardiac Troponin I 6 Hours Post-PCI	0.58 Microgram per liter Standard Deviation 1.310	0.13 Microgram per liter Standard Deviation 0.354	0.08 Microgram per liter Standard Deviation 0.204
Change From Baseline to Post-PCI for Cardiac Troponin I 24 Hours Post- PCI/Discharge	-0.03 Microgram per liter Standard Deviation 0.197	5.50 Microgram per liter Standard Deviation NA Standard deviation could not be calculated for only one participant.	0.30 Microgram per liter Standard Deviation 0.300

SECONDARY outcome

Timeframe: At 6 hours and 24 hours post-PCI/discharge on Day 1

Population: Safety Set included all participants in the FAS who received any study treatment. Combined data for Stage A and Stage B is presented as pre-specified in protocol. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here 'Number Analyzed' indicates number of participants evaluable at the specified timepoints.

Procedural myocardial injury was defined as elevation of cardiac troponin (cTn) values greater than (\>) 99th percentile upper reference limit (URL) in participants with normal baseline values (\<= 99th percentile URL) or elevation of cTn by \> 20% of the baseline value in participants with elevated cTn levels (\>99th percentile URL).

Outcome measures

Outcome measures
Measure	Temanogrel 20 mg n=10 Participants Participants received a single intravenous (IV) dose of temanogrel 20 mg on Day 1 following which the participants underwent percutaneous coronary intervention (PCI). Participants had a follow-up phone call 7 days after administration of study treatment.	Temanogrel 40 mg n=8 Participants Participants received a single IV dose of temanogrel 40mg on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Placebo n=9 Participants Participants received a single IV dose of placebo on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.
Number of Participants With Procedural Myocardial Injury 6 Hours Post-PCI	3 Participants	1 Participants	1 Participants
Number of Participants With Procedural Myocardial Injury 24 Hours Post-PCI/Discharge	1 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Pre-PCI, anytime between 0 to 15 minutes,1 hour, 3 hours, 6 hours post-PCI and 24 hours post PCI/discharge

Population: Pharmacokinetic (PK) set included all participants in the Safety Set with at least 1 post dose PK measurement. Here, 'Number Analyzed' signifies number of participants evaluable at the specified timepoints. Combined data for Stage A and Stage B is presented as pre-specified in protocol.

Observed plasma concentration of temanogrel. Lower limit of quantification (LLOQ) of temanogrel was 0.500 nanograms/milliliter (ng/mL).

Outcome measures

Outcome measures
Measure	Temanogrel 20 mg n=10 Participants Participants received a single intravenous (IV) dose of temanogrel 20 mg on Day 1 following which the participants underwent percutaneous coronary intervention (PCI). Participants had a follow-up phone call 7 days after administration of study treatment.	Temanogrel 40 mg n=8 Participants Participants received a single IV dose of temanogrel 40mg on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Placebo Participants received a single IV dose of placebo on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.
Concentration of Temanogrel Pre-PCI	1558.3889 Nanograms per milliliter Standard Deviation 2156.89423	1869.8571 Nanograms per milliliter Standard Deviation 1815.65878	—
Concentration of Temanogrel 0 to 15 minutes post PCI	126.9900 Nanograms per milliliter Standard Deviation 31.08320	265.0000 Nanograms per milliliter Standard Deviation 109.83260	—
Concentration of Temanogrel 1 hour post PCI	84.8667 Nanograms per milliliter Standard Deviation 24.45278	134.1667 Nanograms per milliliter Standard Deviation 36.56455	—
Concentration of Temanogrel 3 hours post PCI	41.8500 Nanograms per milliliter Standard Deviation 17.23969	87.1714 Nanograms per milliliter Standard Deviation 90.12348	—
Concentration of Temanogrel 6 hours post PCI	24.6522 Nanograms per milliliter Standard Deviation 19.78224	36.9000 Nanograms per milliliter Standard Deviation 14.94380	—
Concentration of Temanogrel 24 hours post-procedure/discharge	NA Nanograms per milliliter Standard Deviation NA Data were not calculated as all values were below the limit of detection.	—	—

SECONDARY outcome

Timeframe: Pre-PCI, anytime between 0 to 15 minutes,1 hour, 3 hours, 6 hours post-PCI and 24 hours post PCI/discharge

Population: PK set will include all participants in the Safety Set with at least 1 post dose PK measurement. Here, 'Number Analyzed' signifies number of participants evaluable at the specified timepoints. Combined data for Stage A and Stage B is presented as pre-specified in protocol.

Observed plasma concentration of AR295980.

Outcome measures

Outcome measures
Measure	Temanogrel 20 mg n=10 Participants Participants received a single intravenous (IV) dose of temanogrel 20 mg on Day 1 following which the participants underwent percutaneous coronary intervention (PCI). Participants had a follow-up phone call 7 days after administration of study treatment.	Temanogrel 40 mg n=8 Participants Participants received a single IV dose of temanogrel 40mg on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Placebo Participants received a single IV dose of placebo on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.
Concentration of AR295980 Pre-PCI	1.0472 Nanograms per milliliter Standard Deviation 0.87240	3.2010 Nanograms per milliliter Standard Deviation 3.97562	—
Concentration of AR295980 0 to 15 minutes post PCI	6.3680 Nanograms per milliliter Standard Deviation 2.61560	6.8183 Nanograms per milliliter Standard Deviation 2.24211	—
Concentration of AR295980 1 hour post PCI	5.0750 Nanograms per milliliter Standard Deviation 1.81783	8.0783 Nanograms per milliliter Standard Deviation 4.32397	—
Concentration of AR295980 3 hours post PCI	3.6933 Nanograms per milliliter Standard Deviation 1.18230	5.5300 Nanograms per milliliter Standard Deviation 2.48489	—
Concentration of AR295980 6 hours post PCI	2.4678 Nanograms per milliliter Standard Deviation 0.79325	5.2650 Nanograms per milliliter Standard Deviation 3.21979	—
Concentration of AR295980 24 hours post-PCI/discharge	0.3518 Nanograms per milliliter Standard Deviation 0.40765	—	—

SECONDARY outcome

Timeframe: Pre-PCI, anytime between 0 to 15 minutes,1 hour, 3 hours, 6 hours post-PCI and 24 hours post PCI/discharge

Population: PK set included all participants in the Safety Set with at least 1 post dose PK measurement. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here, 'Number Analyzed' signifies number of participants evaluable at the specified timepoints. Combined data for Stage A and Stage B is presented as pre-specified in protocol.

Observed plasma concentration of AR295981.

Outcome measures

Outcome measures
Measure	Temanogrel 20 mg n=10 Participants Participants received a single intravenous (IV) dose of temanogrel 20 mg on Day 1 following which the participants underwent percutaneous coronary intervention (PCI). Participants had a follow-up phone call 7 days after administration of study treatment.	Temanogrel 40 mg n=8 Participants Participants received a single IV dose of temanogrel 40mg on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Placebo Participants received a single IV dose of placebo on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.
Concentration of AR295981 6 hours post PCI	0.2899 Nanograms per milliliter Standard Deviation 0.35198	0.8685 Nanograms per milliliter Standard Deviation 0.51239	—
Concentration of AR295981 24 hours post-PCI/discharge	NA Nanograms per milliliter Standard Deviation NA Data were not calculated as all values were below the limit of detection.	—	—
Concentration of AR295981 Pre-PCI	1.8042 Nanograms per milliliter Standard Deviation 1.11941	5.9129 Nanograms per milliliter Standard Deviation 8.69909	—
Concentration of AR295981 0 to 15 minutes post PCI	0.9032 Nanograms per milliliter Standard Deviation 0.46521	1.9030 Nanograms per milliliter Standard Deviation 1.05032	—
Concentration of AR295981 1 hour post PCI	0.6743 Nanograms per milliliter Standard Deviation 0.36798	1.6575 Nanograms per milliliter Standard Deviation 0.73395	—
Concentration of AR295981 3 hours post PCI	0.4677 Nanograms per milliliter Standard Deviation 0.37748	1.0651 Nanograms per milliliter Standard Deviation 0.32193	—

SECONDARY outcome

Timeframe: From start of study treatment on day 1 to up to maximum of 10 days

Population: The safety set included all participants in the FAS who received any study treatment. Combined data for Stage A and Stage B is presented as pre-specified in protocol.

An adverse event (AE) was any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. TEAE was an AE that occurred after initiation of study treatment that was not present at the time of treatment start or an AE that increased in severity after the initiation of medication, if the event was present at the time of treatment start emerges. AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 as grade 1: mild; grade 2: moderate; grade 3: severe, grade 4: life threatening, grade 5: death related to AE. Number of participants with any TEAE and grade 3 or higher TEAE have been reported.

Outcome measures

Outcome measures
Measure	Temanogrel 20 mg n=10 Participants Participants received a single intravenous (IV) dose of temanogrel 20 mg on Day 1 following which the participants underwent percutaneous coronary intervention (PCI). Participants had a follow-up phone call 7 days after administration of study treatment.	Temanogrel 40 mg n=8 Participants Participants received a single IV dose of temanogrel 40mg on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Placebo n=9 Participants Participants received a single IV dose of placebo on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity Any TEAE	4 Participants	7 Participants	4 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity Grade 3 or higher TEAE	0 Participants	2 Participants	1 Participants

SECONDARY outcome

Timeframe: From start of study treatment on day 1 to up to maximum of 10 days

Population: The safety set included all participants in the FAS who received any study treatment. Combined data for Stage A and Stage B is presented as pre-specified in protocol.

An AE was any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. TEAE was an AE that occurred after initiation of study treatment that was not present at the time of treatment start or an AE that increased in severity after the initiation of medication, if the event was present at the time of treatment start emerges. SAE was an AE resulting in any of the following outcomes or considered medically significant: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or birth defect. Relatedness was based on investigator's assessment.

Outcome measures

Outcome measures
Measure	Temanogrel 20 mg n=10 Participants Participants received a single intravenous (IV) dose of temanogrel 20 mg on Day 1 following which the participants underwent percutaneous coronary intervention (PCI). Participants had a follow-up phone call 7 days after administration of study treatment.	Temanogrel 40 mg n=8 Participants Participants received a single IV dose of temanogrel 40mg on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Placebo n=9 Participants Participants received a single IV dose of placebo on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.
Number of Participants With Serious Adverse Events (SAEs), Adverse Events Leading to Discontinuation of Study Treatment and Treatment-Related TEAEs SAEs	0 Participants	2 Participants	1 Participants
Number of Participants With Serious Adverse Events (SAEs), Adverse Events Leading to Discontinuation of Study Treatment and Treatment-Related TEAEs Adverse events leading to discontinuation of study treatment	0 Participants	0 Participants	0 Participants
Number of Participants With Serious Adverse Events (SAEs), Adverse Events Leading to Discontinuation of Study Treatment and Treatment-Related TEAEs Treatment-Related TEAEs	1 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From start of study treatment on day 1 to up to maximum of 10 days

Population: The safety set included all participants in the FAS who received any study treatment. Combined data for Stage A and Stage B is presented as pre-specified in protocol.

An adverse event was any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. TEAE was an AE that occurred after initiation of study treatment that was not present at the time of treatment start or an AE that increased in severity after the initiation of medication, if the event was present at the time of treatment start emerges. Relatedness was based on investigator's assessment.

Outcome measures

Outcome measures
Measure	Temanogrel 20 mg n=10 Participants Participants received a single intravenous (IV) dose of temanogrel 20 mg on Day 1 following which the participants underwent percutaneous coronary intervention (PCI). Participants had a follow-up phone call 7 days after administration of study treatment.	Temanogrel 40 mg n=8 Participants Participants received a single IV dose of temanogrel 40mg on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Placebo n=9 Participants Participants received a single IV dose of placebo on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.
Number of Participants With Treatment-Related TEAEs According to the Preferred Term Hypertension	0 Participants	1 Participants	0 Participants
Number of Participants With Treatment-Related TEAEs According to the Preferred Term Vascular access site haematoma	1 Participants	0 Participants	0 Participants

Adverse Events

Temanogrel 20 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Temanogrel 40 mg

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Temanogrel 20 mg n=10 participants at risk Participants received a single intravenous (IV) dose of temanogrel 20 mg on Day 1 following which the participants underwent percutaneous coronary intervention (PCI). Participants had a follow-up phone call 7 days after administration of study treatment.	Temanogrel 40 mg n=8 participants at risk Participants received a single IV dose of temanogrel 40mg on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.	Placebo n=9 participants at risk Participants received a single IV dose of placebo on Day 1 following which the participants underwent PCI. Participants had a follow-up phone call 7 days after administration of study treatment.
Injury, poisoning and procedural complications Vascular access site haematoma	0.00% 0/10 • From start of study treatment on Day 1 to up to maximum of 10 days Same event may appear as both non-SAE and SAE but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other, or a participant may have experienced both serious and non-serious event.	12.5% 1/8 • From start of study treatment on Day 1 to up to maximum of 10 days Same event may appear as both non-SAE and SAE but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other, or a participant may have experienced both serious and non-serious event.	0.00% 0/9 • From start of study treatment on Day 1 to up to maximum of 10 days Same event may appear as both non-SAE and SAE but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other, or a participant may have experienced both serious and non-serious event.
Vascular disorders Aortic dissection	0.00% 0/10 • From start of study treatment on Day 1 to up to maximum of 10 days Same event may appear as both non-SAE and SAE but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other, or a participant may have experienced both serious and non-serious event.	12.5% 1/8 • From start of study treatment on Day 1 to up to maximum of 10 days Same event may appear as both non-SAE and SAE but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other, or a participant may have experienced both serious and non-serious event.	0.00% 0/9 • From start of study treatment on Day 1 to up to maximum of 10 days Same event may appear as both non-SAE and SAE but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other, or a participant may have experienced both serious and non-serious event.
Cardiac disorders Acute myocardial infarction	0.00% 0/10 • From start of study treatment on Day 1 to up to maximum of 10 days Same event may appear as both non-SAE and SAE but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other, or a participant may have experienced both serious and non-serious event.	0.00% 0/8 • From start of study treatment on Day 1 to up to maximum of 10 days Same event may appear as both non-SAE and SAE but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other, or a participant may have experienced both serious and non-serious event.	11.1% 1/9 • From start of study treatment on Day 1 to up to maximum of 10 days Same event may appear as both non-SAE and SAE but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other, or a participant may have experienced both serious and non-serious event.

Other adverse events

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER