Microvascular Obstruction
Conditions
Keywords
Temanogrel, Microvascular obstruction, APD791, Percutaneous coronary intervention, MVO, PCI
Brief summary
The purpose of this study is to determine whether intravenous temanogrel is a safe and effective treatment for microvascular obstruction (MVO) in adult participants undergoing percutaneous coronary intervention (PCI).
Detailed description
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study to be conducted in 2 stages (Stage A and Stage B). Stage A is an ascending single-dose placebo-controlled study planned to consist of 2 cohorts. Stage B is a parallel-treatment group study planned to consist of a placebo group and 2 active treatment groups of temanogrel doses selected based on safety and tolerability data in Stage A.
Interventions
DRUGTemanogrel
Participants will receive a single intravenous dose of temanogrel on Day 1 (Day 1 of PCI procedure)
DRUGPlacebo
Participants will receive a single intravenous dose of temanogrel matching placebo on Day 1
Sponsors
Arena is a wholly owned subsidiary of Pfizer
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Stable angina participants suitable for elective PCI, or participants suitable for PCI for diagnosis of non-ST-elevation myocardial infarction or unstable angina (NSTEMI/UA) who are consistently hemodynamically stable until the time of PCI and have a thrombolysis in myocardial infarction (TIMI) Flow Grade 2 or 3 on the diagnostic angiography * Target lesions for PCI must appear suitable for stenting as confirmed on the diagnostic angiography and must satisfy the study criteria regarding lesion size and vessel diameter/type. * Females must not be of childbearing potential * Males with pregnant or non-pregnant female partners of childbearing potential must agree to using a condom during treatment and for 90 days following treatment
Exclusion criteria
* Planned or anticipated use of rotational atherectomy/ablation or shockwave therapies during the PCI procedure * Any history of stroke, seizure, intracranial bleeding, or intracranial aneurysm * Transient ischemic attack within the 6 months prior to Screening * History of major trauma, major surgery, and/or clinically significant head injury or hemorrhage within the last 6 months of Screening * Any ST-elevation myocardial infarction (STEMI) within 10 days of Screening or STEMI within the target vessel territory within the last 4 months of Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Index of Microcirculatory Resistance (IMR) From Baseline to Post Percutaneous Coronary Intervention (PCI) | From Baseline (prior to administration of study treatment) to 15 minutes post-PCI on Day 1 | 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) \* \[1.34 \* mean distal coronary pressure at maximum hyperemia (Pd)/Pa minus 0.32\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Post-PCI for Fractional Flow Reserve (FFR) | From Baseline (prior to administration of study treatment) to 15 minutes post-PCI on Day 1 | The FFR was calculated from the ratio of distal to proximal mean pressures at maximal hyperemia (FFR = \[distal coronary pressure/aortic pressure at maximum hyperemia\]). |
| Change From Baseline to Post-PCI for Corrected Thrombolysis in Myocardial Infarction Frame Count (cTFC) | From Baseline (prior to administration of study treatment) to 15 minutes post-PCI on Day 1 | 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. |
| Number of Participants According to Change From Baseline to Post-PCI for Thrombolysis in Myocardial Infarction (TIMI) Flow Grade (TFG) Post-PCI | Baseline (prior to administration of study treatment) and anytime between 0 to 15 minutes post-PCI on Day 1 | 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. |
| Number of Participants According to Change From Baseline to Post-PCI in Thrombolysis in Myocardial Infarction Myocardial Perfusion Grade (TMPG) Post-PCI | Baseline (prior to administration of study treatment) and anytime between 0 to 15 minutes post-PCI on Day 1 | 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. |
| Change From Baseline to Post-PCI for Creatine Kinase (CK) | Baseline (prior to administration of study treatment), anytime between 0 to 15 minutes, 6 hours post-PCI, and 24 hours post-PCI/discharge | — |
| Change From Baseline to Post-PCI for Creatine Kinase-Myocardial Band (CK-MB) | Baseline (prior to administration of study treatment), anytime between 0 to 15 minutes, 6 hours post-PCI and 24 hours post-PCI/discharge | — |
| Change From Baseline to Post-PCI for Cardiac Troponin I | Baseline (prior to administration of study treatment), anytime between 0 to 15 minutes, 6 hours post-PCI and 24 hours post-PCI/discharge | — |
| Change From Baseline to Post-PCI for Coronary Flow Reserve (CFR) | From Baseline (prior to administration of study treatment) to 15 minutes post-PCI on Day 1 | The coronary flow reserve (CFR) was calculated from the ratio of baseline (i.e., resting transit time) to hyperemic mean transit time. |
| Concentration of Temanogrel | Pre-PCI, anytime between 0 to 15 minutes,1 hour, 3 hours, 6 hours post-PCI and 24 hours post PCI/discharge | Observed plasma concentration of temanogrel. Lower limit of quantification (LLOQ) of temanogrel was 0.500 nanograms/milliliter (ng/mL). |
| Concentration of AR295980 | Pre-PCI, anytime between 0 to 15 minutes,1 hour, 3 hours, 6 hours post-PCI and 24 hours post PCI/discharge | Observed plasma concentration of AR295980. |
| Concentration of AR295981 | Pre-PCI, anytime between 0 to 15 minutes,1 hour, 3 hours, 6 hours post-PCI and 24 hours post PCI/discharge | Observed plasma concentration of AR295981. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | From start of study treatment on day 1 to up to maximum of 10 days | 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. |
| Number of Participants With Serious Adverse Events (SAEs), Adverse Events Leading to Discontinuation of Study Treatment and Treatment-Related TEAEs | From start of study treatment on day 1 to up to maximum of 10 days | 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. |
| Number of Participants With Treatment-Related TEAEs According to the Preferred Term | From start of study treatment on day 1 to up to maximum of 10 days | 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. |
| Number of Participants With Procedural Myocardial Injury | At 6 hours and 24 hours post-PCI/discharge on Day 1 | 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). |
Countries
Australia, Netherlands, Sweden, United Kingdom, United States
Participant flow
Recruitment details
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.
Pre-assignment details
A total of 29 participants were enrolled and randomized in the study.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 10 |
| 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. | 10 |
| 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. | 9 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Fractional flow not significant | 0 | 1 | 0 |
| Overall Study | Unable to proceed to study procedure | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Temanogrel 20 mg | Temanogrel 40 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 65.9 Years STANDARD_DEVIATION 7.81 | 64.5 Years STANDARD_DEVIATION 3.27 | 63.3 Years STANDARD_DEVIATION 9.63 | 64.6 Years STANDARD_DEVIATION 7.12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 9 Participants | 9 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 7 Participants | 8 Participants | 9 Participants | 24 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Male | 9 Participants | 10 Participants | 6 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 8 | 0 / 9 |
| other Total, other adverse events | 4 / 10 | 7 / 8 | 3 / 9 |
| serious Total, serious adverse events | 0 / 10 | 2 / 8 | 1 / 9 |
Outcome results
Primary
Change in Index of Microcirculatory Resistance (IMR) From Baseline to Post Percutaneous Coronary Intervention (PCI)
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) \* \[1.34 \* mean distal coronary pressure at maximum hyperemia (Pd)/Pa minus 0.32\].
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temanogrel 20 mg | 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 |
| Temanogrel 40 mg | Change in Index of Microcirculatory Resistance (IMR) From Baseline to Post Percutaneous Coronary Intervention (PCI) | 0.0691 Millimeter of mercury*seconds | Standard Deviation 13.27702 |
| Placebo | Change in Index of Microcirculatory Resistance (IMR) From Baseline to Post Percutaneous Coronary Intervention (PCI) | -1.8907 Millimeter of mercury*seconds | Standard Deviation 18.82659 |
Secondary
Change From Baseline to Post-PCI for Cardiac Troponin I
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Temanogrel 20 mg | 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 |
| Temanogrel 20 mg | Change From Baseline to Post-PCI for Cardiac Troponin I | 24 Hours Post- PCI/Discharge | -0.03 Microgram per liter | Standard Deviation 0.197 |
| Temanogrel 20 mg | Change From Baseline to Post-PCI for Cardiac Troponin I | 6 Hours Post-PCI | 0.58 Microgram per liter | Standard Deviation 1.31 |
| Temanogrel 40 mg | Change From Baseline to Post-PCI for Cardiac Troponin I | 0 to 15 minutes Post-PCI | 0.01 Microgram per liter | Standard Deviation 0.035 |
| Temanogrel 40 mg | Change From Baseline to Post-PCI for Cardiac Troponin I | 6 Hours Post-PCI | 0.13 Microgram per liter | Standard Deviation 0.354 |
| Temanogrel 40 mg | Change From Baseline to Post-PCI for Cardiac Troponin I | 24 Hours Post- PCI/Discharge | 5.50 Microgram per liter | — |
| Placebo | Change From Baseline to Post-PCI for Cardiac Troponin I | 0 to 15 minutes Post-PCI | 0.04 Microgram per liter | Standard Deviation 0.052 |
| Placebo | Change From Baseline to Post-PCI for Cardiac Troponin I | 24 Hours Post- PCI/Discharge | 0.30 Microgram per liter | Standard Deviation 0.3 |
| Placebo | Change From Baseline to Post-PCI for Cardiac Troponin I | 6 Hours Post-PCI | 0.08 Microgram per liter | Standard Deviation 0.204 |
Secondary
Change From Baseline to Post-PCI for Coronary Flow Reserve (CFR)
The coronary flow reserve (CFR) was calculated from the ratio of baseline (i.e., resting transit time) to hyperemic mean transit time.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temanogrel 20 mg | Change From Baseline to Post-PCI for Coronary Flow Reserve (CFR) | 1.2744 Ratio | Standard Deviation 0.89307 |
| Temanogrel 40 mg | Change From Baseline to Post-PCI for Coronary Flow Reserve (CFR) | 1.0238 Ratio | Standard Deviation 2.97729 |
| Placebo | Change From Baseline to Post-PCI for Coronary Flow Reserve (CFR) | 1.3787 Ratio | Standard Deviation 1.4044 |
Secondary
Change From Baseline to Post-PCI for Corrected Thrombolysis in Myocardial Infarction Frame Count (cTFC)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temanogrel 20 mg | Change From Baseline to Post-PCI for Corrected Thrombolysis in Myocardial Infarction Frame Count (cTFC) | -6.54 Frames per second | Standard Deviation 7.365 |
| Temanogrel 40 mg | Change From Baseline to Post-PCI for Corrected Thrombolysis in Myocardial Infarction Frame Count (cTFC) | -0.81 Frames per second | Standard Deviation 6.32 |
| Placebo | Change From Baseline to Post-PCI for Corrected Thrombolysis in Myocardial Infarction Frame Count (cTFC) | -8.93 Frames per second | Standard Deviation 8.368 |
Secondary
Change From Baseline to Post-PCI for Creatine Kinase (CK)
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Temanogrel 20 mg | Change From Baseline to Post-PCI for Creatine Kinase (CK) | 6 hours post-PCI | 0.9 Units per liter | Standard Deviation 17.2 |
| Temanogrel 20 mg | 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 |
| Temanogrel 20 mg | Change From Baseline to Post-PCI for Creatine Kinase (CK) | 24 hours post- PCI/discharge | -33.7 Units per liter | Standard Deviation 23.42 |
| Temanogrel 40 mg | Change From Baseline to Post-PCI for Creatine Kinase (CK) | 6 hours post-PCI | 1.5 Units per liter | Standard Deviation 27.07 |
| Temanogrel 40 mg | Change From Baseline to Post-PCI for Creatine Kinase (CK) | 0 to 15 minutes post-PCI | -6.0 Units per liter | Standard Deviation 5.68 |
| Temanogrel 40 mg | Change From Baseline to Post-PCI for Creatine Kinase (CK) | 24 hours post- PCI/discharge | 233.0 Units per liter | — |
| Placebo | Change From Baseline to Post-PCI for Creatine Kinase (CK) | 0 to 15 minutes post-PCI | -5.9 Units per liter | Standard Deviation 10.58 |
| Placebo | Change From Baseline to Post-PCI for Creatine Kinase (CK) | 24 hours post- PCI/discharge | -6.0 Units per liter | Standard Deviation 38.94 |
| Placebo | Change From Baseline to Post-PCI for Creatine Kinase (CK) | 6 hours post-PCI | -23.5 Units per liter | Standard Deviation 41.03 |
Secondary
Change From Baseline to Post-PCI for Creatine Kinase-Myocardial Band (CK-MB)
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Temanogrel 20 mg | Change From Baseline to Post-PCI for Creatine Kinase-Myocardial Band (CK-MB) | 6 Hours Post-PCI | 0.70 Micrograms per liter | Standard Deviation 1.26 |
| Temanogrel 20 mg | 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 0.29 |
| Temanogrel 20 mg | 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 |
| Temanogrel 40 mg | Change From Baseline to Post-PCI for Creatine Kinase-Myocardial Band (CK-MB) | 6 Hours Post-PCI | 0.79 Micrograms per liter | Standard Deviation 2.208 |
| Temanogrel 40 mg | 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 0.225 |
| Temanogrel 40 mg | Change From Baseline to Post-PCI for Creatine Kinase-Myocardial Band (CK-MB) | 24 Hours Post- PCI/Discharge | 31.80 Micrograms per liter | — |
| Placebo | Change From Baseline to Post-PCI for Creatine Kinase-Myocardial Band (CK-MB) | 0 to 15 minutes Post-PCI | -0.26 Micrograms per liter | Standard Deviation 0.49 |
| Placebo | Change From Baseline to Post-PCI for Creatine Kinase-Myocardial Band (CK-MB) | 24 Hours Post- PCI/Discharge | 0.97 Micrograms per liter | Standard Deviation 0.643 |
| Placebo | Change From Baseline to Post-PCI for Creatine Kinase-Myocardial Band (CK-MB) | 6 Hours Post-PCI | -0.63 Micrograms per liter | Standard Deviation 1.359 |
Secondary
Change From Baseline to Post-PCI for Fractional Flow Reserve (FFR)
The FFR was calculated from the ratio of distal to proximal mean pressures at maximal hyperemia (FFR = \[distal coronary pressure/aortic pressure at maximum hyperemia\]).
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temanogrel 20 mg | Change From Baseline to Post-PCI for Fractional Flow Reserve (FFR) | 0.1346 Ratio | Standard Deviation 0.1962 |
| Temanogrel 40 mg | Change From Baseline to Post-PCI for Fractional Flow Reserve (FFR) | 0.2494 Ratio | Standard Deviation 0.20758 |
| Placebo | Change From Baseline to Post-PCI for Fractional Flow Reserve (FFR) | 0.3123 Ratio | Standard Deviation 0.16562 |
Secondary
Concentration of AR295980
Observed plasma concentration of AR295980.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Temanogrel 20 mg | Concentration of AR295980 | Pre-PCI | 1.0472 Nanograms per milliliter | Standard Deviation 0.8724 |
| Temanogrel 20 mg | Concentration of AR295980 | 0 to 15 minutes post PCI | 6.3680 Nanograms per milliliter | Standard Deviation 2.6156 |
| Temanogrel 20 mg | Concentration of AR295980 | 1 hour post PCI | 5.0750 Nanograms per milliliter | Standard Deviation 1.81783 |
| Temanogrel 20 mg | Concentration of AR295980 | 3 hours post PCI | 3.6933 Nanograms per milliliter | Standard Deviation 1.1823 |
| Temanogrel 20 mg | Concentration of AR295980 | 6 hours post PCI | 2.4678 Nanograms per milliliter | Standard Deviation 0.79325 |
| Temanogrel 20 mg | Concentration of AR295980 | 24 hours post-PCI/discharge | 0.3518 Nanograms per milliliter | Standard Deviation 0.40765 |
| Temanogrel 40 mg | Concentration of AR295980 | Pre-PCI | 3.2010 Nanograms per milliliter | Standard Deviation 3.97562 |
| Temanogrel 40 mg | Concentration of AR295980 | 6 hours post PCI | 5.2650 Nanograms per milliliter | Standard Deviation 3.21979 |
| Temanogrel 40 mg | Concentration of AR295980 | 0 to 15 minutes post PCI | 6.8183 Nanograms per milliliter | Standard Deviation 2.24211 |
| Temanogrel 40 mg | Concentration of AR295980 | 3 hours post PCI | 5.5300 Nanograms per milliliter | Standard Deviation 2.48489 |
| Temanogrel 40 mg | Concentration of AR295980 | 1 hour post PCI | 8.0783 Nanograms per milliliter | Standard Deviation 4.32397 |
Secondary
Concentration of AR295981
Observed plasma concentration of AR295981.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Temanogrel 20 mg | Concentration of AR295981 | 0 to 15 minutes post PCI | 0.9032 Nanograms per milliliter | Standard Deviation 0.46521 |
| Temanogrel 20 mg | Concentration of AR295981 | 6 hours post PCI | 0.2899 Nanograms per milliliter | Standard Deviation 0.35198 |
| Temanogrel 20 mg | Concentration of AR295981 | 1 hour post PCI | 0.6743 Nanograms per milliliter | Standard Deviation 0.36798 |
| Temanogrel 20 mg | Concentration of AR295981 | 3 hours post PCI | 0.4677 Nanograms per milliliter | Standard Deviation 0.37748 |
| Temanogrel 20 mg | Concentration of AR295981 | 24 hours post-PCI/discharge | NA Nanograms per milliliter | — |
| Temanogrel 20 mg | Concentration of AR295981 | Pre-PCI | 1.8042 Nanograms per milliliter | Standard Deviation 1.11941 |
| Temanogrel 40 mg | Concentration of AR295981 | 6 hours post PCI | 0.8685 Nanograms per milliliter | Standard Deviation 0.51239 |
| Temanogrel 40 mg | Concentration of AR295981 | 0 to 15 minutes post PCI | 1.9030 Nanograms per milliliter | Standard Deviation 1.05032 |
| Temanogrel 40 mg | Concentration of AR295981 | Pre-PCI | 5.9129 Nanograms per milliliter | Standard Deviation 8.69909 |
| Temanogrel 40 mg | Concentration of AR295981 | 1 hour post PCI | 1.6575 Nanograms per milliliter | Standard Deviation 0.73395 |
| Temanogrel 40 mg | Concentration of AR295981 | 3 hours post PCI | 1.0651 Nanograms per milliliter | Standard Deviation 0.32193 |
Secondary
Concentration of Temanogrel
Observed plasma concentration of temanogrel. Lower limit of quantification (LLOQ) of temanogrel was 0.500 nanograms/milliliter (ng/mL).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Temanogrel 20 mg | Concentration of Temanogrel | Pre-PCI | 1558.3889 Nanograms per milliliter | Standard Deviation 2156.89423 |
| Temanogrel 20 mg | Concentration of Temanogrel | 0 to 15 minutes post PCI | 126.9900 Nanograms per milliliter | Standard Deviation 31.0832 |
| Temanogrel 20 mg | Concentration of Temanogrel | 1 hour post PCI | 84.8667 Nanograms per milliliter | Standard Deviation 24.45278 |
| Temanogrel 20 mg | Concentration of Temanogrel | 3 hours post PCI | 41.8500 Nanograms per milliliter | Standard Deviation 17.23969 |
| Temanogrel 20 mg | Concentration of Temanogrel | 6 hours post PCI | 24.6522 Nanograms per milliliter | Standard Deviation 19.78224 |
| Temanogrel 20 mg | Concentration of Temanogrel | 24 hours post-procedure/discharge | NA Nanograms per milliliter | — |
| Temanogrel 40 mg | Concentration of Temanogrel | Pre-PCI | 1869.8571 Nanograms per milliliter | Standard Deviation 1815.65878 |
| Temanogrel 40 mg | Concentration of Temanogrel | 6 hours post PCI | 36.9000 Nanograms per milliliter | Standard Deviation 14.9438 |
| Temanogrel 40 mg | Concentration of Temanogrel | 0 to 15 minutes post PCI | 265.0000 Nanograms per milliliter | Standard Deviation 109.8326 |
| Temanogrel 40 mg | Concentration of Temanogrel | 3 hours post PCI | 87.1714 Nanograms per milliliter | Standard Deviation 90.12348 |
| Temanogrel 40 mg | Concentration of Temanogrel | 1 hour post PCI | 134.1667 Nanograms per milliliter | Standard Deviation 36.56455 |
Secondary
Number of Participants According to Change From Baseline to Post-PCI for Thrombolysis in Myocardial Infarction (TIMI) Flow Grade (TFG) Post-PCI
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Temanogrel 20 mg | 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 |
| Temanogrel 20 mg | 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 |
| Temanogrel 20 mg | 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 |
| Temanogrel 40 mg | 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 | 8 Participants |
| Temanogrel 40 mg | 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 | 0 Participants |
| Temanogrel 40 mg | 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 | 8 Participants |
| Placebo | 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 | 8 Participants |
| Placebo | 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 | 9 Participants |
| Placebo | 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 |
Secondary
Number of Participants According to Change From Baseline to Post-PCI in Thrombolysis in Myocardial Infarction Myocardial Perfusion Grade (TMPG) Post-PCI
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Temanogrel 20 mg | 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 |
| Temanogrel 20 mg | 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 |
| Temanogrel 20 mg | 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 |
| Temanogrel 20 mg | 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 |
| Temanogrel 20 mg | 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 |
| Temanogrel 40 mg | 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 | 4 Participants |
| Temanogrel 40 mg | Number of Participants According to Change From Baseline to Post-PCI in Thrombolysis in Myocardial Infarction Myocardial Perfusion Grade (TMPG) Post-PCI | Baseline Missing | 4 Participants |
| Temanogrel 40 mg | 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 | 6 Participants |
| Temanogrel 40 mg | 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 | 2 Participants |
| Temanogrel 40 mg | 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 | 0 Participants |
| Placebo | 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 | 6 Participants |
| Placebo | 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 | 3 Participants |
| Placebo | 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 |
| Placebo | Number of Participants According to Change From Baseline to Post-PCI in Thrombolysis in Myocardial Infarction Myocardial Perfusion Grade (TMPG) Post-PCI | Baseline Missing | 5 Participants |
| Placebo | 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 | 3 Participants |
Secondary
Number of Participants With Procedural Myocardial Injury
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).
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Temanogrel 20 mg | Number of Participants With Procedural Myocardial Injury | 24 Hours Post-PCI/Discharge | 1 Participants |
| Temanogrel 20 mg | Number of Participants With Procedural Myocardial Injury | 6 Hours Post-PCI | 3 Participants |
| Temanogrel 40 mg | Number of Participants With Procedural Myocardial Injury | 6 Hours Post-PCI | 1 Participants |
| Temanogrel 40 mg | Number of Participants With Procedural Myocardial Injury | 24 Hours Post-PCI/Discharge | 1 Participants |
| Placebo | Number of Participants With Procedural Myocardial Injury | 6 Hours Post-PCI | 1 Participants |
| Placebo | Number of Participants With Procedural Myocardial Injury | 24 Hours Post-PCI/Discharge | 2 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs), Adverse Events Leading to Discontinuation of Study Treatment and Treatment-Related TEAEs
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Temanogrel 20 mg | 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 |
| Temanogrel 20 mg | Number of Participants With Serious Adverse Events (SAEs), Adverse Events Leading to Discontinuation of Study Treatment and Treatment-Related TEAEs | SAEs | 0 Participants |
| Temanogrel 20 mg | 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 |
| Temanogrel 40 mg | 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 |
| Temanogrel 40 mg | Number of Participants With Serious Adverse Events (SAEs), Adverse Events Leading to Discontinuation of Study Treatment and Treatment-Related TEAEs | SAEs | 2 Participants |
| Temanogrel 40 mg | 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 |
| Placebo | 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 |
| Placebo | Number of Participants With Serious Adverse Events (SAEs), Adverse Events Leading to Discontinuation of Study Treatment and Treatment-Related TEAEs | Treatment-Related TEAEs | 0 Participants |
| Placebo | Number of Participants With Serious Adverse Events (SAEs), Adverse Events Leading to Discontinuation of Study Treatment and Treatment-Related TEAEs | SAEs | 1 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Temanogrel 20 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Any TEAE | 4 Participants |
| Temanogrel 20 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Grade 3 or higher TEAE | 0 Participants |
| Temanogrel 40 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Any TEAE | 7 Participants |
| Temanogrel 40 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Grade 3 or higher TEAE | 2 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Any TEAE | 4 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Grade 3 or higher TEAE | 1 Participants |
Secondary
Number of Participants With Treatment-Related TEAEs According to the Preferred Term
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Temanogrel 20 mg | Number of Participants With Treatment-Related TEAEs According to the Preferred Term | Vascular access site haematoma | 1 Participants |
| Temanogrel 20 mg | Number of Participants With Treatment-Related TEAEs According to the Preferred Term | Hypertension | 0 Participants |
| Temanogrel 40 mg | Number of Participants With Treatment-Related TEAEs According to the Preferred Term | Hypertension | 1 Participants |
| Temanogrel 40 mg | Number of Participants With Treatment-Related TEAEs According to the Preferred Term | Vascular access site haematoma | 0 Participants |
| Placebo | Number of Participants With Treatment-Related TEAEs According to the Preferred Term | Hypertension | 0 Participants |
| Placebo | Number of Participants With Treatment-Related TEAEs According to the Preferred Term | Vascular access site haematoma | 0 Participants |