The objection of the study is to assess the safety, tolerability, and effect on microvascular obstruction of study drug in subjects undergoing Percutaneous Coronary Intervention.NL specific sub-study:The aim of this substudy is to investigate…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint:
• Change in IMR from Baseline to Post PCI
Secondary outcome
Secondary endpoints:
• Change from Baseline to Post PCI with the study drug versus placebo for the
following assessments:
- Coronary physiology indices (coronary flow reserve [CFR], fractional
flow reserve [FFR])
- Angiographic measures (corrected thrombolysis in myocardial infarction
frame count [cTFC], TFG, thrombolysis in myocardial infarction
myocardial perfusion grade [TMPG])
- Myocardial injury markers (creatine kinase [CK], creatine kinase
myocardial band [CK MB], cTn)
• The incidence of procedural myocardial injury
• Observed Maximum Plasma Concentration (Cmax) of study drug and its
Metabolites;
• Safety and tolerability of the study drug
Background summary
During a percutaneous coronary intervention procedure, a short wire-mesh tube,
called a stent, is inserted into the narrowed or blocked coronary artery (a big
blood vessel that supplies the blood to the heart). This opens the artery and
allows blood to flow more freely. However, in some people, blood flow within
the heart does not return to healthy levels even after this procedure. It is
thought this may be due to a condition called microvascular obstruction (MVO).
Microvascular obstruction is associated with poor recovery from this type of
procedure. Several treatment options for MVO have been explored but none have
been proven to help in preventing or treating MVO after a PCI. Therefore, there
is a need to develop and find new therapies to prevent or treat MVO in people
undergoing PCI treatment for CAD.
Study objective
The objection of the study is to assess the safety, tolerability, and effect on
microvascular obstruction of study drug in subjects undergoing Percutaneous
Coronary Intervention.
NL specific sub-study:
The aim of this substudy is to investigate changes in Rµ and MRR from Baseline
(prior to percutaneous coronary intervention [PCI] and administration of study
treatment) to Pre-PCI (following study treatment administration ie, post-drug
but pre-PCI) and Post-PCI (following PCI). These assessments will be performed
immediately following measurements of IMR at sites participating in this
substudy using the same Coroventis software utilized in the parent APD791-202
study. It is anticipated this may provide assessment of the coronary
microcirculation that is complementary to, but distinct from, IMR.
Specifically, these measures may provide insight into the effect of temanogrel
on microcirculation at resting conditions, which may not be apparent during
adenosine-induced hyperemia utilized when performing IMR assessments, as well
as providing an absolute assessment of microvascular resistance.
Study design
This is a Phase 2, multicenter, randomized, double blind, placebo controlled
study to be conducted in 2 stages (Stage A and Stage B). Each stage includes a
Screening Period of up to 14 days, a single dose of randomized study treatment
(temanogrel or placebo) on Day 1, and a Follow Up phone call 7 days (± 2 days)
after administration of study treatment for a total study duration of 6 to 24
days.
Intervention
The study drug is an IV formulation containing active pharmaceutical ingredient
provided as 25 mg/mL strength. Subjects will receive a single IV dose of study
treatment on Day 1 of the study.
The study drug dose to be administered to Cohort 1 of Stage A will be 20 mg.
The dose administered in Cohort 2 is planned to be 40 mg. Selected doses from
Stage A are planned to be investigated in Stage B of the study
Study burden and risks
As of the date of this protocol, the safety, tolerability, PK, and PD of the
study drug have been assessed in 5 Phase 1 studies. Single and repeated doses
of oral study drug were evaluated in 4 studies, and single IV doses of the
study drug were evaluated in a separate study. In completed clinical studies,
doses of study drug planned to be used in this study were well-tolerated and
there were no associated safety concerns
Nancy Ridge Drive 6154
San Diego, California 92121
US
Nancy Ridge Drive 6154
San Diego, California 92121
US
Listed location countries
Age
Inclusion criteria
- Stable angina patients suitable for elective PCI or patients suitable for PCI
for diagnosis of NSTEMI/UA. NSTEMI/UA patients are to be 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. Acceptable lesions cannot be in the left main artery or
in a vein or arterial graft, or be a chronic total occlusion or in-stent
restenosis. Two or more sequential lesions may be treated in the same artery,
as long as they are treated in the same session and at least one of the lesions
meets inclusion criteria:
• For elective PCI patients and non-urgent NSTEMI/UA patients (PCI >12 hours
after diagnosis), the lesion must be located in a >= 2.75 mm diameter coronary
artery; the lesion must also be >= 18 mm long and require the use of one or more
stents that in total must be >= 20 mm long.
• For NSTEMI patients treated with PCI urgently (within 12 hours after
diagnosis), the coronary artery diameter of the culprit lesion must be >= 2.75
mm.
- Both men and women participants agree to use a highly effective method of
birth control throughout the entire study period, from informed consent through
the adverse
event reporting period, if the possibility of conception exists
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 6 months of Screening
(eg, a patient with a NSTEMI because of a lesion in a diagonal may not be
included if there is a history of anterior STEMI due to left anterior
descending artery lesion that occurred within the last 6 months);
- Known history of heart failure with reduced ejection fraction (HFrEF) defined
as left
ventricular ejection fraction <= 40% prior to current hospital admission.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-000238-16-NL |
| CCMO | NL75791.100.20 |