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

• Sponsor: Arena Pharmaceuticals (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04848220
• Collaborator: (none)
• Enrollment: 99
• Locations: 12
• Arms: 3
• Anticipated Duration (Months): 14.9
• Patients Per Site: 8.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Microvascular Obstruction	Drug: Temanogrel; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 99 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Jun 3, 2021
• Anticipated Primary Completion Date: Sep 1, 2022
• Anticipated Study Completion Date: Sep 1, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in Index of Microcirculatory Resistance (IMR) From Baseline to Post-PCI [Baseline (prior to administration of study treatment) to Post-PCI on Day 1]

Secondary Outcome Measures

1. Change From Baseline to Post-PCI for Other Coronary Physiology Indices [Baseline (prior to administration of study treatment) to Post-PCI on Day 1]

   Coronary physiology indices include coronary flow reserve (CFR) and fractional flow reserve (FFR).

2. Change From Baseline to Post-PCI for Angiographic Measures [Baseline (prior to administration of study treatment) to Post-PCI on Day 1]

   The analysis of the target vessel angiographic measures include corrected thrombolysis in myocardial infarction frame count (cTFC), thrombolysis in myocardial infarction flow grade (TFG), and thrombolysis in myocardial infarction myocardial perfusion grade (TMPG).

3. Change From Baseline to Post-PCI for Myocardial Injury Markers [Baseline (prior to administration of study treatment) to Post-PCI on Day 1]

   Myocardial injury markers include creatine kinase (CK), creatine kinase-myocardial band (CK-MB), and cardiac troponin (cTn).

4. Incidence of Procedural Myocardial Injury [Baseline (prior to administration of study treatment) and at 6 and 24 hours Post-PCI]

5. Observed Maximum Plasma Concentration (Cmax) of Temanogrel and Active Metabolites AR295980 and AR295981 [Baseline (prior to administration of study treatment); Pre-PCI; and at 1, 3, 6 and 24 hours Post-PCI]

6. Number and Severity of Adverse Events [Study Day 1 through Study Day 8]

   Safety will be assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tibor Rubin VA Medical Center	Long Beach	California	United States	90822-5201
2	VA Palo Alto - Cardiac Catheterization Laboratory	Palo Alto	California	United States	94304
3	University of Chicago Medical Center	Chicago	Illinois	United States	60637
4	Royal Prince Alfred Hospital	Camperdown	New South Wales	Australia	2050
5	Concord Repatriation General Hospital	Concord	New South Wales	Australia	2139
6	Alfred Health - The Alfred Hospital	Melbourne	Victoria	Australia	3004
7	Royal Perth Hospital	Perth	Western Australia	Australia	6000
8	Radboud University Medical Center	Nijmegen	Gelderland	Netherlands	6525 GA
9	Maasstad Hospital	Rotterdam	South Holland	Netherlands	3079 DZ
10	Catharina Ziekenhuis	Eindhoven		Netherlands	5623 EJ
11	Skåne University Hospital	Lund		Sweden	221 85
12	East and North Hertfordshire NHS Trust Lister Hospital	Stevenage		United Kingdom	SG1 4AB

Sponsors and Collaborators

• Arena Pharmaceuticals

Investigators

• Study Director: Arena CT.gov Administrator, Arena Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Arena Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04848220
• Other Study ID Numbers: APD791-202
• First Posted: Apr 19, 2021
• Last Update Posted: Jul 18, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Arena Pharmaceuticals: Temanogrel; Microvascular obstruction; APD791; Percutaneous coronary intervention; MVO; PCI
• Additional relevant MeSH terms: APD791

Study Results

No Results Posted as of Jul 18, 2022