Effectiveness of CRD-740 in Heart Failure | NCT05409183 | Trialant
NCT05409183
Sponsor
Cardurion Pharmaceuticals, Inc.
Status
Terminated
Last Update Posted
Dec 19, 2024Actual
Enrollment
60Actual
Phase
Phase 2
Conditions
Heart Failure
Heart Failure With Reduced Ejection Fraction
Heart Failure With Preserved Ejection Fraction
Cardiovascular Diseases
Heart Diseases
Interventions
CRD-740
Placebo
Countries
United States
Canada
Israel
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT05409183
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CRD-740-201
Secondary IDs
Not provided
Brief Title
Effectiveness of CRD-740 in Heart Failure
Official Title
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Clinical Study to Assess the Effectiveness of CRD-740 in Subjects With Chronic Heart Failure (CARDINAL-HF)
Acronym
CARDINAL-HF
Organization
Cardurion Pharmaceuticals, Inc.INDUSTRY
Status Module
Record Verification Date
Nov 2024
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Part A of the study was successfully concluded. Part B of the study was not conducted in favor of redesigned new studies.
Expanded Access Info
No
Start Date
May 26, 2022Actual
Primary Completion Date
May 2, 2023Actual
Completion Date
Jul 25, 2023Actual
First Submitted Date
Jun 3, 2022
First Submission Date that Met QC Criteria
Jun 3, 2022
First Posted Date
Jun 8, 2022Actual
Results Waived
Not provided
Results First Submitted Date
Aug 22, 2024
Results First Submitted that Met QC Criteria
Nov 26, 2024
Results First Posted Date
Dec 19, 2024Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Nov 26, 2024
Last Update Posted Date
Dec 19, 2024Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Cardurion Pharmaceuticals, Inc.INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This is a study evaluating the effectiveness of CRD-740 in patients with either Heart Failure with Reduced Ejection Fraction (HFrEF) or Heart Failure with Preserved Ejection Fraction (HFpEF) after 12 weeks of treatment. The primary objective in Part A is to assess the effect of CRD-740 compared to placebo in plasma cGMP at Week 4 in HFrEF.
Part B of the study was not conducted in favor of redesigned new studies.
Detailed Description
Not provided
Conditions Module
Conditions
Heart Failure
Heart Failure With Reduced Ejection Fraction
Heart Failure With Preserved Ejection Fraction
Cardiovascular Diseases
Heart Diseases
Keywords
PDE9
Heart Failure
CRD-740
HFpEF
HFrEF
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
60Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
CRD-740
Experimental
Part A: Participants in Part A randomly assigned to this arm will take CRD-740 at two ascending dose levels over 12 weeks.
Drug: CRD-740
Placebo
Placebo Comparator
Part A: Participants in Part A randomly assigned to this arm will take placebo at two ascending dose levels over 12 weeks.
Drug: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
CRD-740
Drug
Tablets administered orally.
CRD-740
Placebo
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Part A: The Mean Change From Baseline (Day 1) in Plasma cGMP at Week 4.
Efficacy: To assess the effect of CRD-740 compared to placebo in plasma cGMP at Week 4 in subjects with CHFrEF.
Baseline to Week 4
Secondary Outcomes
Not provided
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Males or Females ≥18 years of age, at screening.
Diagnosis of clinical heart failure syndrome, New York Heart Association functional class II - III for at least 6 months prior to screening
For Part A:
Ejection Fraction ≤40% by echocardiography at screening.
NT-proBNP level ≥600 pg/ml at screening. Subjects with atrial fibrillation or flutter at screening are required to have an NT-proBNP level of ≥1000 pg/mL at screening.
5. Stable doses of guideline-directed heart failure therapy for a minimum of 4 weeks prior to screening that has been individually optimized according to standard practice guidelines and no addition of guideline-directed heart failure therapy within 3 months of screening.
Exclusion Criteria:
2. Recent HF exacerbation defined by hospitalization or requirement for intravenous diuretics within 60 days of screening.
3. Subjects with planned interventions (e.g., percutaneous coronary intervention, devices) etc. occurring during their involvement in this study.
4. Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major cardiovascular surgery or carotid angioplasty within 60 days of screening.
5. Subjects with clinical suspicion of infiltrative cardiomyopathy (e.g., amyloid, sarcoid), hypertrophic cardiomyopathy (obstructive or non-obstructive), or HF secondary to severe valvular disease, active myocarditis, active pericarditis, or clinically significant congenital heart disease.
6. Prior or planned orthotopic heart transplantation.
7. Presence of or plan for mechanical circulatory support.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Udelson JE, Belohlavek J, Dukat A, Ezekowitz J, Goland S, Merkely B, O'Meara E, Petrie MC, Ponikowski P, Senni M, Tokmakova M, Vardeny O, Claggett B, Moore E, Savard M, McKellar H, Surks HK, Solomon SD, McMurray JJV. Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of CRD-740, a PDE9 Inhibitor, in Chronic Heart Failure. JACC Heart Fail. 2026 Jan;14(1):102706. doi: 10.1016/j.jchf.2025.102706. Epub 2025 Oct 31.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
Plan to Share IPD
No
Description
Not provided
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
Not provided
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
CRD-740
Part A: Participants in Part A randomly assigned to this arm will take CRD-740 at two ascending dose levels over 12 weeks.
CRD-740: Tablets administered orally.
Part B of the study was not conducted in favor of redesigned new studies.
Part A: Participants in Part A randomly assigned to this arm will take placebo at two ascending dose levels over 12 weeks.
Placebo: Tablets administered orally.
Part B of the study was not conducted in favor of redesigned new studies.
FG00040 subjects
FG00120 subjects
COMPLETED
FG00040 subjects
FG00120 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
Period 2
Type
Comment
Milestone Data
STARTED
FG00040 subjects
FG00120 subjects
COMPLETED
FG00038 subjects
FG00119 subjects
NOT COMPLETED
FG0002 subjects
FG0011 subjects
Period 3
Type
Comment
Milestone Data
STARTED
FG00038 subjects
FG00119 subjects
COMPLETED
FG00036 subjects
FG00119 subjects
NOT COMPLETED
FG0002 subjects
FG0010 subjects
Complete Study
Type
Comment
Milestone Data
STARTED
FG00040 subjects
FG00120 subjects
COMPLETED
FG00036 subjects
FG00118 subjects
NOT COMPLETED
FG0004 subjects
FG0012 subjects
Type
Comment
Reasons
Adverse Event
FG0001 subjects
FG0012 subjects
Withdrawal by Subject
FG0003 subjects
FG001
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
CRD-740
Part A: Participants in Part A randomly assigned to this arm will take CRD-740 at two ascending dose levels over 12 weeks.
CRD-740: Tablets administered orally.
Part B of the study was not conducted in favor of redesigned new studies.
BG001
Placebo
Part A: Participants in Part A randomly assigned to this arm will take placebo at two ascending dose levels over 12 weeks.
Placebo: Tablets administered orally.
Part B of the study was not conducted in favor of redesigned new studies.
BG002
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00040
BG00120
BG00260
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00040
ParticipantsBG00120
ParticipantsBG00260
Title
Measurements
<=18 years
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
ParticipantsBG00040
ParticipantsBG00120
ParticipantsBG002
Age, Customized
Median
Full Range
years
Title
Denominators
Categories
Median Age
ParticipantsBG00040
ParticipantsBG00120
ParticipantsBG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00040
ParticipantsBG00120
ParticipantsBG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00040
ParticipantsBG00120
ParticipantsBG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00040
ParticipantsBG00120
ParticipantsBG002
Region of Enrollment
Number
participants
Title
Denominators
Categories
United States
ParticipantsBG00040
ParticipantsBG00120
ParticipantsBG002
Mean Height (cm) at Baseline
Mean
Standard Deviation
cm
Title
Denominators
Categories
ParticipantsBG00040
ParticipantsBG00120
ParticipantsBG002
Median Height (cm) at Baseline
Median
Full Range
cm
Title
Denominators
Categories
ParticipantsBG00040
ParticipantsBG00120
ParticipantsBG002
Reproductive System Findings Test (Female only), n (%)
Female population only
Count of Participants
Participants
Title
Denominators
Categories
Childbearing Potential
ParticipantsBG0005
ParticipantsBG0014
ParticipantsBG002
Mean Weight (kg) at Baseline
Mean
Standard Deviation
kg
Title
Denominators
Categories
ParticipantsBG00040
ParticipantsBG00120
ParticipantsBG002
Median Weight (kg) at Baseline
Median
Full Range
kg
Title
Denominators
Categories
ParticipantsBG00040
ParticipantsBG00120
ParticipantsBG002
Mean Body Mass Index (kg/m2) at Baseline
Mean
Standard Deviation
body weight (kg)/ height (m2)
Title
Denominators
Categories
ParticipantsBG00040
ParticipantsBG00120
ParticipantsBG002
Median Body Mass Index (kg/m2) at Baseline
Median
Full Range
body weight (kg)/ height (m2)
Title
Denominators
Categories
ParticipantsBG00040
ParticipantsBG00120
ParticipantsBG002
Echocardiogram performed during screening
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00040
ParticipantsBG00120
ParticipantsBG002
EF group
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00040
ParticipantsBG00120
ParticipantsBG002
Mean EF (%) for rEF (≤40%) subjects
Mean
Standard Deviation
percent
Title
Denominators
Categories
ParticipantsBG00040
ParticipantsBG00120
ParticipantsBG002
Median EF (%) for rEF (≤40%) subjects
Median
Full Range
percent
Title
Denominators
Categories
ParticipantsBG00040
ParticipantsBG00120
ParticipantsBG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Part A: The Mean Change From Baseline (Day 1) in Plasma cGMP at Week 4.
Efficacy: To assess the effect of CRD-740 compared to placebo in plasma cGMP at Week 4 in subjects with CHFrEF.
The modified Intention to Treat (mITT) Population will consist of all randomized subjects who received at least one dose of CRD-740 or placebo. Subjects will be analyzed according to their randomized treatment, regardless of actual treatment received, treatment compliance, or treatment duration.
Posted
Mean
Standard Deviation
AUC 0-6hr (hr*nmol/L)
Baseline to Week 4
ID
Title
Description
OG000
CRD-740
Part A: Participants in Part A randomly assigned to this arm will take CRD-740 at two ascending dose levels over 12 weeks.
CRD-740: Tablets administered orally.
OG001
Placebo
Part A: Participants in Part A randomly assigned to this arm will take placebo at two ascending dose levels over 12 weeks.
Placebo: Tablets administered orally.
Units
Counts
Participants
OG00030
OG00115
Title
Denominators
Categories
Title
Measurements
OG00019.139± 26.9007
OG001-8.822± 31.3357
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
ANCOVA
0.0032
LS Mean of Treatment Difference
26.473
Standard Error of the Mean
9.2160
2-Sided
95
7.847
45.099
Other
Time Frame
Through week 12 plus a 4-week follow-up period.
Description
For Part A, the primary safety analysis was performed by reporting the exposure-adjusted incidence rates in subject-years for AEs and SAEs defined as the number of subjects with that particular AE or SAE within an SOC or PT during the relevant period divided by the sum of the at-risk times.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Period 1: CRD-740
CRD-740 10 mg was administered BID to randomly assigned participants in this period from Day 1 through Day 14.
0
40
1
40
1
40
EG001
Period 1: Placebo
CRD-740 10 mg matching placebo was administered BID to randomly assigned participants in this period from Day 1 through Day 14.
0
20
0
20
1
20
EG002
Period 2: CRD-740
CRD-740 25 mg was administered BID to randomly assigned participants in this period from Day 15 through Day 28.
0
38
1
38
3
38
EG003
Period 2: Placebo
CRD-740 25 mg matching placebo was administered BID to randomly assigned participants in this period from Day 15 through Day 28.
0
19
0
19
1
19
EG004
Period 3: CRD-740
CRD-740 25 mg was administered BID to randomly assigned participants in this period from Day 29 through Day 84.
0
36
0
36
4
36
EG005
Period 3: Placebo
CRD-740 25 mg matching placebo was administered BID to randomly assigned participants in this period from Day 29 through Day 84.
0
19
1
19
1
19
EG006
Overall CRD-740
Part A: Participants in Part A randomly assigned to this arm will take CRD-740 at two ascending dose levels over 12 weeks plus a 4-week follow-up period.
CRD-740: Tablets administered orally.
Part B of the study was not conducted in favor of redesigned new studies.
0
40
3
40
5
40
EG007
Overall Placebo
Part A: Participants in Part A randomly assigned to this arm will take placebo at two ascending dose levels over 12 weeks plus a 4-week follow-up period.
Placebo: Tablets administered orally.
Part B of the study was not conducted in favor of redesigned new studies.
0
20
3
20
3
20
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Pneumonia
Infections and infestations
Systematic Assessment
EG0000 events0 affected40 at risk
EG0010 events0 affected20 at risk
EG0021 events1 affected38 at risk
EG0030 events0 affected19 at risk
EG0040 events0 affected36 at risk
EG0050 events0 affected19 at risk
EG0061 events1 affected40 at risk
EG0071 events1 affected20 at risk
Influenza
Infections and infestations
Systematic Assessment
EG0001 events1 affected40 at risk
EG0010 events0 affected20 at risk
EG0020 events0 affected38 at risk
EG003
Cerebrovascular accident
Nervous system disorders
Systematic Assessment
EG0000 events0 affected40 at risk
EG0010 events0 affected20 at risk
EG0020 events0 affected38 at risk
EG003
Cardiac failure congestive
Cardiac disorders
Systematic Assessment
EG0000 events0 affected40 at risk
EG0010 events0 affected20 at risk
EG0020 events0 affected38 at risk
EG003
Ventricular tachycardia
Cardiac disorders
Systematic Assessment
EG0000 events0 affected40 at risk
EG0010 events0 affected20 at risk
EG0020 events0 affected38 at risk
EG003
Acute respiratory failure
Respiratory, thoracic and mediastinal disorders
Systematic Assessment
EG0000 events0 affected40 at risk
EG0010 events0 affected20 at risk
EG0020 events0 affected38 at risk
EG003
Renal mass
Renal and urinary disorders
Systematic Assessment
EG0000 events0 affected40 at risk
EG0010 events0 affected20 at risk
EG0020 events0 affected38 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Hypokalaemia
Metabolism and nutrition disorders
Systematic Assessment
EG0000 events0 affected40 at risk
EG0010 events0 affected20 at risk
EG0021 events1 affected38 at risk
EG0030 events0 affected19 at risk
EG0040 events0 affected36 at risk
EG0050 events0 affected19 at risk
EG0061 events1 affected40 at risk
EG0070 events0 affected20 at risk
Dizziness postural
Nervous system disorders
Systematic Assessment
EG0000 events0 affected40 at risk
EG0011 events1 affected20 at risk
EG0020 events0 affected38 at risk
EG003
Scleritis
Eye disorders
Systematic Assessment
EG0000 events0 affected40 at risk
EG0010 events0 affected20 at risk
EG0020 events0 affected38 at risk
EG003
Vertigo
Ear and labyrinth disorders
Systematic Assessment
EG0000 events0 affected40 at risk
EG0010 events0 affected20 at risk
EG0020 events0 affected38 at risk
EG003
Dry throat
Respiratory, thoracic and mediastinal disorders
Systematic Assessment
EG0001 events1 affected40 at risk
EG0010 events0 affected20 at risk
EG0020 events0 affected38 at risk
EG003
Throat irritation
Respiratory, thoracic and mediastinal disorders
Systematic Assessment
EG0001 events1 affected40 at risk
EG0010 events0 affected20 at risk
EG0020 events0 affected38 at risk
EG003
Abdominal pain
Gastrointestinal disorders
Systematic Assessment
EG0000 events0 affected40 at risk
EG0010 events0 affected20 at risk
EG0021 events1 affected38 at risk
EG003
Diarrhea
Gastrointestinal disorders
Systematic Assessment
EG0000 events0 affected40 at risk
EG0010 events0 affected20 at risk
EG0022 events1 affected38 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0000 events0 affected40 at risk
EG0010 events0 affected20 at risk
EG0020 events0 affected38 at risk
EG003
Haematuria
Renal and urinary disorders
Systematic Assessment
EG0000 events0 affected40 at risk
EG0010 events0 affected20 at risk
EG0020 events0 affected38 at risk
EG003
Overdose
Injury, poisoning and procedural complications
Systematic Assessment
EG0000 events0 affected40 at risk
EG0010 events0 affected20 at risk
EG0020 events0 affected38 at risk
EG003
This study was planned to have been conducted in 2 parts: Part A and Part B. Part A was a dose ranging study in a group of subjects with CHFrEF. Part B was planned to be a proof-of-concept study in subjects with either CHFrEF or CHFpEF. Part B of the study was not conducted in favor of redesigned new studies.