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Trial registered on ANZCTR


Registration number
ACTRN12616000120471
Ethics application status
Approved
Date submitted
29/01/2016
Date registered
3/02/2016
Date last updated
22/01/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluating the Plasma Pharmacokinetics of CRD-102 in patients with Heart Failure following long term administration
Scientific title
Evaluating the Plasma Pharmacokinetics of CRD-102 in patients with Heart Failure following long term administration
Secondary ID [1] 288446 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiovascular - heart failure 297473 0
Condition category
Condition code
Cardiovascular 297659 297659 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
There are 2 arms to this study. Each arm will enrol up to 15 patients. Patients will be assigned to be administered 14mg twice daily of CRD-102, or 18mg of CRD-102 twice daily.
Patients will be administered CRD-102 for 30 days prior to a PK study that will be done on day 30.
CRD-102 will be administered as a capsule. Patients will be dispensed adequate supply of medication when the study commences. Any unused tablets will need to be returned - thus ensuring compliance. Laboratory tests to measure levels on day 30 will give an indication of plasma levels at baseline. There will also be an outpatient visit during the trial, where patient will be reminded to be compliant to study treatment regime.

An additional 3rd arm of up to 15 patients may be enrolled if required following an interim analysis. The 3rd arm will receive oral CRD-102 twice daily for 30 days at a dose to be determined based on interim analysis.
Intervention code [1] 293774 0
Treatment: Drugs
Comparator / control treatment
This is an active only trial. Patients will be assigned to be administered 14mg of CRD-102 twice daily, or 18mg of CRD-102 twice daily. A 3rd arm may be enrolled, where patients will be assigned CRD-102 twice daily at a dose to be determined.
Control group
Dose comparison

Outcomes
Primary outcome [1] 297194 0
To evaluate the pharmacokinetics of CRD-102 following long term administration.
These parameters are assessed by blood sample, and is assesed via measuring: Trough level concentration, Cmax, Tmax, T1/2 (half life), elimination rate, AUC exposure
Timepoint [1] 297194 0
30 days
PK will be analysed at pre-dose (0 hr), and at 1, 2, 3, 4, 6, 8, 10 and 12 hours following administration of CRD-102
Secondary outcome [1] 320301 0
To evaluate the effects of CRD-102 on NT-BNP levels (serum assay)
Timepoint [1] 320301 0
30 days. This will be assessed on day 30, sample to be taken pre-dose on day 30.
Secondary outcome [2] 320302 0
To evaluate the effects of CRD-102 on renal function (blood tests - lab testing of electrolytes, urea and creatinine)
Timepoint [2] 320302 0
At pre-dose on day 30
Secondary outcome [3] 320303 0
To evaluate the effects of CRD-102 on 6 minute walk test
Timepoint [3] 320303 0
this will be done on day 30, after the administration of the morning dose of CRD-102
Secondary outcome [4] 320304 0
To evaluate the effects of CRD-102 on ICD activity. This will be done via interrogation of the ICD via an ICD interrogator, sensor that subsequently transmit all relevant information to a computing device, where a report will be generated for physician review
Timepoint [4] 320304 0
THis will be done on day 30, following administration of the morning dose of CRD-102

Eligibility
Key inclusion criteria
1. Subject is at least 18 years of age
2. HF consistent with NYHA class II - IV
3. Subject has a known history of HF (more than 12 months in duration) and had at least 1 hospitalization for HF in the past 3 months
4. Subject has left ventricular ejection fraction (LVEF) less than 35%
5. Subject is receiving optimal medical therapy as tolerated according to the subject’s physician
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. subject has had a myocardial infarct (MI) within 90 days before Screening
2. Subject is listed for heart transplant or a LVAD
3. Subject has a systolic blood pressure less than 90 mm Hg
4. Subject has, at Screening, significant hepatic disease (serum total bilirubin equal or more than 3.0 mg/dL [equal or more than 51.3 micromol/L), renal disease (eGFR less than 30 mL/min), or hematologic, gastrointestinal, immunologic, endocrine, metabolic, or central nervous system disease
5. Subject is symptomatically too unwell to be considered for trial, as evidenced by 6MWT less than 150m
6. Subject has undergone cardiac surgery within the 60 days before Screening
7. Symptomatic ventricular arrhythmia or ICD firing within 60 days before Screening
8. Subjects who are receiving flecainide, encainide, propafenone, dofetilide, or disopyramide
9. Subjects who have received within 7 days before the Screening or dosing visits:
a. An IV positive inotropic agent
b. A human B-type natriuretic peptide, including nesiritide
c. An oral or IV phosphodiesterase III inhibitor (PDEI III), including levosimendan and cilostazol
10. Subjects who have the following laboratory results at screening
a. Serum potassium concentration less than 4.0 or more than 5.5 mEq/L (less than 4.0 or more than 5.5 mmol/L)
b. Serum magnesium concentration less than 1.0 mEq/L (less than 0.5 mmol/L)
c. Serum digoxin concentration more than 1.2 ng/mL (more than 1.5 nmol/L)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
The first 15 patients enrolled into the trial will be assigned the 14mg twice daily oral dosing arm. The subsequent 15 patients enrolled into the trial will be assigned the 18mg twice daily oral dosing arm. Following interim analysis, a 3rd arm may be recruited, where up to 15 patients will be enrolled to be administered a dose of CRD-102 twice daily, at a dose to be guided by the interim analysis of PK results.
Phase
Phase 1
Type of endpoint(s)
Pharmacokinetics
Statistical methods / analysis
Given that this is primarily a PK trial, up to 15 patients per arm is required to obtain enough data to study the PK profile of CRD-102. No statistical analysis was required. to determine sample size.

Detailed PK analysis will be done to yield standard PK parameters including Cmax, tmax, AUC, t 1/2 , Vd and Cl.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 12666 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 292791 0
Commercial sector/Industry
Name [1] 292791 0
Cardiora Pty Ltd
Address [1] 292791 0
Level 9, 31 Queen Street, Melbourne, VIC, 3000
Country [1] 292791 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Cardiora Pty Ltd
Address
Level 9, 278 Collins Street, Melbourne, VIC 3000
Country
Australia
Secondary sponsor category [1] 291529 0
None
Name [1] 291529 0
none
Address [1] 291529 0
none
Country [1] 291529 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294283 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 294283 0
55 Commercial Road, Melbourne 3004, VIC
Ethics committee country [1] 294283 0
Australia
Date submitted for ethics approval [1] 294283 0
25/01/2016
Approval date [1] 294283 0
22/03/2016
Ethics approval number [1] 294283 0

Summary
Brief summary
The intention of the trial is to study the pharmacokinetics (PK) of CRD-102 in patients with heart failure following 30 days of administration.

It is hypothesized that CRD-102 is able to improve heart function and quality of life. Prior to conducting a phase 2 trial, Cardiora needs to better understand the PK profile of CRD-102, how it is absorbed and cleared from the body.

This trial intends to study the PK effects of different doses of CRD-102. A dose of 14 mg twice daily will be administered to up to 15 patients, and following this 18mg twice daily will be trialled.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 63182 0
Dr Peter Bergin
Address 63182 0
Heart Centre, Alfred Hospital
55 Commercial Road,
Melbourne, VIC 3004
Country 63182 0
Australia
Phone 63182 0
+61390763263
Fax 63182 0
Email 63182 0
P.Bergin@alfred.org.au
Contact person for public queries
Name 63183 0
Dr Bob Soh
Address 63183 0
Cardiora Pty Ltd
Level 9, 31 Queen Street, Melbourne, Vic 3000
Country 63183 0
Australia
Phone 63183 0
+61396570700
Fax 63183 0
Email 63183 0
bob.soh@cardiora.com
Contact person for scientific queries
Name 63184 0
Dr Bob Soh
Address 63184 0
Cardiora Pty Ltd
Level 9, 31 Queen Street, Melbourne, VIC 3000
Country 63184 0
Australia
Phone 63184 0
+61396570700
Fax 63184 0
Email 63184 0
bob.soh@cardiora.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary