A Study Evaluating the Safety, Tolerability, and Effect on Microvascular Obstruction of Intravenous Temanogrel in Adult Participants Undergoing Percutaneous Coronary Intervention
- Conditions
- Microvascular Obstruction
- Interventions
- Drug: TemanogrelDrug: Placebo
- Registration Number
- NCT04848220
- Lead Sponsor
- Pfizer
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 29
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Stage A (Dose Cohort 1) and Stage B (Dose Group 1) Temanogrel - Stage A (Dose Cohort 2) and Stage B (Dose Group 2) Temanogrel - Stage A (Dose Cohort 1 and Dose Cohort 2) and Stage B (Dose Group 1 and Dose Group 2) Placebo -
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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.
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.
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 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).
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.
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 = \[distal coronary pressure/aortic pressure at maximum hyperemia\]).
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-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 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).
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-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.
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 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.
Trial Locations
- Locations (12)
East and North Hertfordshire NHS Trust Lister Hospital
🇬🇧Stevenage, United Kingdom
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
Skåne University Hospital
🇸🇪Lund, Sweden
VA Palo Alto - Cardiac Catheterization Laboratory
🇺🇸Palo Alto, California, United States
Tibor Rubin VA Medical Center
🇺🇸Long Beach, California, United States
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Alfred Health - The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
Catharina Ziekenhuis
🇳🇱Eindhoven, Netherlands
Radboud University Medical Center
🇳🇱Nijmegen, Gelderland, Netherlands
Maasstad Hospital
🇳🇱Rotterdam, South Holland, Netherlands