A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, and Effect on Microvascular Obstruction of Temanogrel in Subjects Undergoing Percutaneous Coronary Intervention
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 29
- 试验地点
- 12
- 主要终点
- Change in Index of Microcirculatory Resistance (IMR) From Baseline to Post Percutaneous Coronary Intervention (PCI)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 30 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Stage A (Dose Cohort 1) and Stage B (Dose Group 1)
干预措施: Temanogrel (Drug)
Stage A (Dose Cohort 2) and Stage B (Dose Group 2)
干预措施: Temanogrel (Drug)
Stage A (Dose Cohort 1 and Dose Cohort 2) and Stage B (Dose Group 1 and Dose Group 2)
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Index of Microcirculatory Resistance (IMR) From Baseline to Post Percutaneous Coronary Intervention (PCI)
时间窗: 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) \* \[1.34 \* mean distal coronary pressure at maximum hyperemia (Pd)/Pa minus 0.32\].
次要结局
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)