- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03370887
AZD8601 Study in CABG Patients
A Randomized, Double-blind, Placebo-controlled, Multi-centre, Sequential Design, Phase IIa Study to Evaluate Safety and Tolerability of Epicardial Injections of AZD8601 During Coronary Artery Bypass Grafting Surgery
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Kuopio, Finland, 70210
- Research Site
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Tampere, Finland, 33520
- Research Site
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Turku, Finland, 20520
- Research Site
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München, Germany, 81675
- Research Site
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München, Germany, 80363
- Research Site
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Groningen, Netherlands, 9713 GZ
- Research Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
For inclusion in the study patients should fulfil the following criteria at Visit 1 and/or 2:
1. Provision of signed and dated informed consent prior to any study specific procedures
Males and females:
- Males must be surgically sterile or using an acceptable method of contraception
- Females must be of non-childbearing potential confirmed at screening by fulfilling one of the following criteria a) postmenopausal defined as amenorrhoea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the postmenopausal range, b) documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation 3. Age >18 years 4. Indication for elective CABG surgery enrolled at least 15 days before the planned surgery 5. Moderately reduced global LVEF at rest (30% ≤ LVEF ≤ 50%) from medical records 6. If patient is on statin, ACE inhibitor/ARB, and/or beta-blocker, the dose should be stable at least 2 weeks prior to Visit 1 7. Patients who are blood donors should not donate blood during the study and for 3 months following their last dose of AZD8601.
Exclusion Criteria:
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) 2. Previous randomisation in the present study 3. Participation in another clinical study with an investigational product during the last 3 months 4. BMI > 35 kg/m2 OR poor image window for echocardiography 5. Need for CABG emergency operation. (Emergency operation is defined as significant symptom status worsening in CAD, such as crescendo angina, unstable angina or ACS requiring rescheduling the revascularization. CAD should be stable at least 3 months prior to Visit 3.) 6. History of ventricular arrhythmia (≥ Lown III) without Implantable Cardiac Defibrillator (ICD) History of any clinically significant disease or disorder which, in the opinion of the PI, may either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study 8. Severe co-morbidities that can interfere with the execution of the study, interpretation of study results or affect the safety of the patient, in judgement of the investigator 9. eGFR ≤ 30 mL/min (derived from creatinine clearance, calculated by local lab) 10. For CFVR (Visit 1) and sMBF (Visit 2) measurement:
- Known severe adverse reactions to adenosine
- Known elevated intracranial pressure
- AV block ≥ second degree and/or sick sinus syndrome in patient without pacemaker
- Heart rate < 40 bpm (ECG verified)
- Systolic blood pressure < 90 mmHg
- Asthma or COPD with strong reactive component in judgement of investigator
Treatment with dipyridamole (e.g. Persantin or Asasantin), theophyllamine or fluvoxamine that cannot be paused 11. Inability to comply with the protocol 12. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity to drugs with a similar chemical structure or class as study drugs 13. Patients unable to give their consent or communicate reliably with the investigator or vulnerable patients e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order 14. Positive hepatitis C antibody hepatitis B virus surface antigen or hepatitis B virus core antibody or human immunodeficiency virus, at Visit 1 15. Known history of drug or alcohol abuse 16. Any concomitant medications that are known to be associated with Torsades de Pointes 17. History of QT prolongation associated with other medications that required discontinuation of that medication 18. Congenital long QT syndrome 19. History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3).
20. Current atrial fibrillation as well as paroxysmal atrial fibrillation.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Low dose AZD8601 (3 mg)
8 patients will be randomised to receive 3 mg AZD8601
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AZD8601 solution for injection, 0,5 mg/mL and 5 mg/mL will be given as 30 injections of 0.1 mg (3 mg per patient), or 1 mg (30 mg per patient) respectively on a single occasion
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Experimental: High dose AZD8601 (30 mg)
8 patients will be randomised to receive 30 mg AZD8601
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AZD8601 solution for injection, 0,5 mg/mL and 5 mg/mL will be given as 30 injections of 0.1 mg (3 mg per patient), or 1 mg (30 mg per patient) respectively on a single occasion
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Placebo Comparator: Placebo
8 patients will be randomised to receive placebo injections
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Placebo for AZ8601 injection for solution will be given as 30 injections per patient on a single occasion
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Serious Adverse Events
Time Frame: Up to 9 months; from signing of ICF at Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP.
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To assess safety and tolerability of AZD8601 given as epicardial injections
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Up to 9 months; from signing of ICF at Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP.
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Adverse event
Time Frame: 6 months, from receiving IP at Visit 3 until 6 months after receiving IP.
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To assess safety and tolerability of AZD8601 given as epicardial injections
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6 months, from receiving IP at Visit 3 until 6 months after receiving IP.
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Electrocardiogram (ECG, number of patients with ECG results exceeding ICH reference ranges)
Time Frame: Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP.
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To assess safety and tolerability of AZD8601 given as epicardial injections
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Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP.
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Left ventricular ejection fraction (LVEF) change from baseline (%)
Time Frame: Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP.
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To assess safety and tolerability of AZD8601 given as epicardial injections
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Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP.
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Changes in physical examination (number of abnormal findings in physical examination)
Time Frame: Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP.
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To assess safety and tolerability of AZD8601 given as epicardial injections
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Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP.
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Changes in vital signs - blood pressure (mmHg)
Time Frame: Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP.
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To assess safety and tolerability of AZD8601 given as epicardial injections
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Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP.
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Changes in vital signs - pulse (bpm)
Time Frame: Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP.
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To assess safety and tolerability of AZD8601 given as epicardial injections
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Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP.
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Changes in laboratory values - hematology
Time Frame: Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP.
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To assess safety and tolerability of AZD8601 given as epicardial injections
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Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP.
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Changes in laboratory values - clinical chemistry
Time Frame: Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP.
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To assess safety and tolerability of AZD8601 given as epicardial injections
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Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP.
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Changes in laboratory values - urinalysis
Time Frame: Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP.
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To assess safety and tolerability of AZD8601 given as epicardial injections
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Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP.
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Vesa Anttila, MD, PhD, Heart Center, Turku University, Finland
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- D9150C00003
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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