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Safety and Tolerability Study of AZD4831 in Patients With Heart Failure. (SATELLITE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03756285
Recruitment Status : Suspended (Study put on hold by sponsor due to current pandemic situation)
First Posted : November 28, 2018
Last Update Posted : May 1, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
A randomized, double-blind, placebo-controlled, parallel group, multicentre study in patients with Heart Failure with preserved Ejection Fraction (HFpEF). The study will be conducted at approximately 15 sites in 5 countries. Approximately 96 patients will be randomized to AZD4831 or placebo (treatment duration 90 days).

Condition or disease Intervention/treatment Phase
Heart Failure Drug: AZD4831 Drug: Placebo Phase 2

Detailed Description:
This is a randomized, double-blind, placebo controlled, parallel group, multicentre study in patients with Heart Failure with preserved Ejection Fraction (HFpEF) and mid-range Ejection Fraction (HRmrEF). The study will be conducted at approximately 15 sites in 5 countries (USA, Sweden, Denmark, Finland, Netherlands). Patients suitable for the study will be checked for eligibility, signing the informed consent and enrolled to the study at visit 1. The study will be divided into two parts, Part A and Part B. In part A 37 patients will be randomized at visit 2 in a 2:1 ratio to once daily dosing of AZD4831 or matching placebo for approximately 90 days. After approximately 30 days of treatment, an interim analysis will be done to analyse the safety, tolerability and target engagement. After the evaluation, the randomization to Part B may proceed. In Part B the approximate 59 remaining patients will be randomized and treated for approximately 90 days.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind, Placebo-controlled, Parallel Group, Multicentre, Phase 2a Study to Assess Target Engagement, Safety and Tolerability of AZD4831 in Patients With Heart Failure With Preserved Ejection Fraction (HFpEF)
Actual Study Start Date : December 11, 2018
Estimated Primary Completion Date : October 13, 2020
Estimated Study Completion Date : October 13, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Experimental: AZD4831
AZD4831 tablets taken orally for for 90 days.
Drug: AZD4831
AZD4831 tablet taken orally for 90 days.

Placebo Comparator: Placebo
Placebo tablets taken orally for 90 days.
Drug: Placebo
Placebo tablet taken orally for 90 days.




Primary Outcome Measures :
  1. The change from baseline in MPO activity in % after AZD4831 treatment. [ Time Frame: Measurements on day 0, 10, 30 and 90. ]
    To compare the effect of AZD4831 to placebo on target engagement


Secondary Outcome Measures :
  1. Change from baseline in CFVR measured in the mid-distal segment of the left anterior descending (LAD) coronary artery under adenosine infusion measured by Transthoracic Doppler Echocardiography (TDE). [ Time Frame: Measurement on day 0 and 90. ]
    To compare the effect of AZD4831 to placebo on coronary flow velocity reserve (CFVR)

  2. Change from baseline in Walking distance [ Time Frame: Measurement on day 0, 30 and 90. ]
    To compare the effect of AZD4831 to placebo on 6 minutes walking test (6MWT)

  3. The pharmacokinetic assessment parameter to be reported is AUC [ Time Frame: Measurement on day 10, 20, 30, 60, 90 and 120. ]
    To assess the pharmacokinetics of AZD4831 after repeated dosing

  4. The Pharmacokinetic assessment parameter to be reported is CL/F. [ Time Frame: Measurment on day 10, 20, 30, 60, 90 and 120. ]
    To assess the pharmatokinetics of AZD4831 after repeated dosing.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   45 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Informed consent

  1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this CSP
  2. Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses

    Age

  3. Patient must be 45 to 85 years of age inclusive, at the time of signing the informed consent form

    Type of patient and disease characteristics

  4. Signs and symptoms of HF in judgement of Investigator AND

    1. Stable NYHA II-IV and
    2. Ejection fraction (EF) ≥ 40 % and
    3. Elevated NT-proBNP or BNP in the last 1 year defined as:

      o Measured as out-patient: NT-proBNP ≥125 ng/L or BNP≥35 ng/L with sinus rhythm, NT-proBNP ≥750 ng/L or BNP ≥200 ng/L with atrial fibrillation (AF),

      or

      o Measured when hospitalized acutely: NT-proBNP ≥500 (ng/L) or BNP ≥125 ng/L with sinus rhythm, NT-proBNP ≥1250 (ng/L) or BNP ≥350 ng/L with AF

    4. And at least one of the following:

      • Hospitalization with HF as primary cause in last 12 months
      • Structural heart disease on echo according to ESC guidelines i.e. either enlarged Left atrial volume index (LAVI > 34 ml/m2) or increased LVM (LVM index > 95 g/m2 in women and > 115 g/m2 in men)
      • Pulmonary capillary wedge pressure (PCWP) at rest >15 mmHg or >25 mmHg at exercise
      • Spectral tissue Doppler echocardiography - E/e' ratio ≥13 at rest

    Weight

  5. Body Mass Index (BMI) range 18-40kg/m2

    Sex

  6. Male or female of nonchildbearing potential

    Reproduction

  7. Female patients must be 1 year post-menopausal or surgically sterile
  8. Male patients must be surgically sterile or using an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of AZD4831/matching placebo to prevent pregnancy in a partner. Male patients must not donate or bank sperm during this same time period

    Genetic sampling

  9. For inclusion in this genetic research, patients must fulfil all of the inclusion criteria described above and provide informed consent for the genetic sampling and analysis

Exclusion Criteria:

Creatinine clearance by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR <30 ml/min/1.73m2 or dialysis

Life expectancy < 3 years due to other reasons than cardiovascular disease

Any ongoing skin disorder, history of or ongoing clinically significant allergy/hypersensitivity.

Current decompensated HF

Primary cardiomyopathy (e.g. constrictive, restrictive, infiltrative, toxic, hypertrophic, congenital or any primary cardiomyopathy) in judgment of investigator

Current hemodynamically significant valve disease in opinion of investigator

EF ever documented < 40%

Any current life-threatening dysrhythmia

Probable alternative primary reason for patient's symptoms in judgment of investigator, including but not limited to:

  1. Isolated pulmonary arterial hypertension or right ventricular (RV) failure; in the absence of left-sided HF
  2. Anaemia: Hb <100 mg/L (10g/dL)
  3. Severe chronic obstructive pulmonary disease (COPD) or lung disease (chronic O2, nebulizer or oral steroid therapy)

Cardiac surgery, acute coronary syndrome (ACS), or non-elective percutaneous coronary intervention (PCI) < 3 months

Known or clinically judged significant macrovascular coronary artery disease (CAD) that has not been revascularized

Heart transplantation or left ventricular assist device ever

Patients with uncontrolled or clinically significant thyroid disease as judged by the investigator.

Alanine transaminase (ALT) or aspartate aminotransferase (AST) ≥2 x upper limit of normal (ULN). Resampling will not be allowed during the same screening period if detected abnormal values do not have reasonable explanation and are not expected to return to normal level within few days.

Known positive HIV, hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03756285


Locations
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United States, Alabama
Research Site
Fort Payne, Alabama, United States, 35967
United States, Georgia
Research Site
Tucker, Georgia, United States, 30084
United States, Illinois
Research Site
Chicago, Illinois, United States, 60611
Research Site
Hazel Crest, Illinois, United States, 60429
United States, Massachusetts
Research Site
Boston, Massachusetts, United States, 02115
Denmark
Research Site
Aarhus N, Denmark, 8200
Research Site
Herlev, Denmark, 2730
Research Site
Hvidovre, Denmark, 2650
Research Site
Odense C, Denmark, 5000
Finland
Research Site
Turku, Finland, 20520
Netherlands
Research Site
Deventer, Netherlands, 7416 SE
Research Site
Dordrecht, Netherlands, 3318 AT
Research Site
Groningen, Netherlands, 9713 GZ
Sweden
Research Site
Göteborg, Sweden, 41345
Research Site
Lund, Sweden, 22242
Research Site
Stockholm, Sweden, 171 76
Sponsors and Collaborators
AstraZeneca
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03756285    
Other Study ID Numbers: D6580C00003
First Posted: November 28, 2018    Key Record Dates
Last Update Posted: May 1, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AstraZeneca:
Heart Failure with Ejection Fraction
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases