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

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

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).

Study Overview

• Status: Terminated
• Conditions: Microvascular Obstruction
• Intervention / Treatment: Drug: Temanogrel; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Health - The Alfred Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
• Netherlands
  • Eindhoven, Netherlands, 5623 EJ
    • Catharina Ziekenhuis
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Radboud university medical center
  • South Holland
    • Rotterdam, South Holland, Netherlands, 3079 DZ
      • Maasstad Hospital
• Sweden
  • Lund, Sweden, 221 85
    • Skane University Hospital
• United Kingdom
  • Stevenage, United Kingdom, SG1 4AB
    • East and North Hertfordshire NHS Trust Lister Hospital
• United States
  • California
    • Long Beach, California, United States, 90822-5201
      • Tibor Rubin VA Medical Center
    • Palo Alto, California, United States, 94304
      • VA Palo Alto - Cardiac Catheterization Laboratory
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage A (Dose Cohort 1) and Stage B (Dose Group 1)	Drug: Temanogrel; Participants will receive a single intravenous dose of temanogrel on Day 1 (Day 1 of PCI procedure)
Experimental: Stage A (Dose Cohort 2) and Stage B (Dose Group 2)	Drug: Temanogrel; Participants will receive a single intravenous dose of temanogrel on Day 1 (Day 1 of PCI procedure)
Placebo Comparator: Stage A (Dose Cohort 1 and Dose Cohort 2) and Stage B (Dose Group 1 and Dose Group 2)	Drug: Placebo; Participants will receive a single intravenous dose of temanogrel matching placebo on Day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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].	From Baseline (prior to administration of study treatment) to 15 minutes post-PCI on Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From Baseline (prior to administration of study treatment) to 15 minutes post-PCI on Day 1
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]).	From Baseline (prior to administration of study treatment) to 15 minutes post-PCI on Day 1
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.	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	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.	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	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.	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 (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
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).	At 6 hours and 24 hours post-PCI/discharge on Day 1
Concentration of Temanogrel	Observed plasma concentration of temanogrel. Lower limit of quantification (LLOQ) of temanogrel was 0.500 nanograms/milliliter (ng/mL).	Pre-PCI, anytime between 0 to 15 minutes,1 hour, 3 hours, 6 hours post-PCI and 24 hours post PCI/discharge
Concentration of AR295980	Observed plasma 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
Concentration of AR295981	Observed plasma 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-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.	From start of study treatment on day 1 to up to maximum of 10 days
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.	From start of study treatment on day 1 to up to maximum of 10 days
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.	From start of study treatment on day 1 to up to maximum of 10 days

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Arena is a wholly owned subsidiary of Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2021
• Primary Completion (Actual): August 23, 2022
• Study Completion (Actual): August 31, 2022

Study Registration Dates

• First Submitted: April 14, 2021
• First Submitted That Met QC Criteria: April 14, 2021
• First Posted (Actual): April 19, 2021

Study Record Updates

• Last Update Posted (Estimated): December 12, 2023
• Last Update Submitted That Met QC Criteria: November 23, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: PCI; Percutaneous coronary intervention; Microvascular obstruction; Temanogrel; APD791; MVO
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; APD791
• Other Study ID Numbers: APD791-202; C5071002 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No