Study of verinurad in heart failure with preserved ejection fraction - AMETHYST

Study identifier:D5496C00005

ClinicalTrials.gov identifier:NCT04327024

EudraCT identifier:2019-004862-16

CTIS identifier:N/A

Study Complete

Official Title

A Phase 2, Multicentre, Double-Blind, Placebo and Active Control Efficacy and Safety Study to Evaluate Verinurad combined with Allopurinol in Heart Failure with Preserved Ejection Fraction

Medical condition

Heart Failure with Preserved Ejection Fraction (HFpEF)

Phase

Phase 2

Healthy volunteers

Study drug

Verinurad, Allopurinol, Placebo for verinurad, Placebo for allopurinol

Sex

All

Actual Enrollment

159

Study type

Interventional

Age

40 Years - 130 Years

Date

Study Start Date: 19 May 2020

Primary Completion Date: 29 Apr 2022

Study Completion Date: 29 Apr 2022

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Jun 2023 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

- Patient must be ≥ 40 years of age at the time of signing the ICF
- Patients with hyperuricaemia defined as sUA level of > 6 mg/dL.
- Patients with documented diagnosis of symptomatic HFpEF according to all of the
following criteria:
(a) Have NYHA functional class II-III at enrolment
(b) Have medical history of typical symptoms/signs of HF > 6 weeks before enrolment
(c) LVEF ≥ 45%
(d) NT-proBNP ≥ 125 pg/mL (≥ 14.75 pmol/L) at Visit 1 for patients without ongoing
atrial fibrillation/flutter.
- Patients able to exercise to near exhaustion during a CPET as exhibited by RER
≥ 1.05 during CPET conducted during screening. If patient does not achieve RER ≥ 1.05 the CPET may be repeated once, at least 48 hours but less than 2 weeks (but before
randomisation) after the initial test; in such cases the second test will serve as baseline.
- Male or female

Exclusion Criteria

- eGFR < 30ml/min/1.73m2 (based on CKD-EPI formula)
- Presence of any condition that precludes exercise testing
- Known history of a documented LVEF < 40%
- Probable alternative or concomitant diagnoses which in the opinion of the Investigator
could account for the patient's HF symptoms and signs (eg, anaemia, hypothyroidism)
- Known carrier of the Human Leukocyte Antigen-B (HLA-B) *58:01 allele: HLA-B
*58:01 genotyping is mandatory prior to randomization for all patients.
- Patients diagnosed with tumor lysis syndrome or Lesch-Nyhan syndrome
- Patients who are severely physically or mentally incapacitated and who in the opinion of
investigator are unable to perform the patients’ tasks associated with the protocol
- Presence of any condition which, in the opinion of the investigator, places the patient at
undue risk or potentially jeopardises the quality of the data to be generated
- Current acute decompensated HF or hospitalisation due to decompensated HF < 4 weeks
prior to enrolment
- Myocardial infarction, unstable angina, coronary revascularisation (percutaneous
coronary intervention or coronary artery bypass grafting), ablation of atrial
flutter/fibrillation, valve repair/replacement, implantation of a cardiac resynchronisation
therapy device, stroke or transient ischemic attack within 6 months prior to enrolment.
- Planned coronary revascularisation, ablation of atrial flutter/fibrillation and/or valve
repair/replacement
- Atrial fibrillation with persistent resting heart rate > 110 beats per minute.

Location

Research Site

Quebec, QC, Canada, G1V 4G5

Location

Research Site

Sofia, Bulgaria, 1431

Location

Research Site

Plovdiv, Bulgaria, 4004

Location

Research Site

Gangwon-do, Republic of Korea, 26426

Location

Research Site

Seoul, Republic of Korea, 03722

Location

Research Site

Quebec, QC, Canada, G2J 0C4

Location

Research Site

Quebec, QC, Canada, G3K 2P8

Location

Research Site

Quebec, QC, Canada, G1G 3Y8

Arms	Assigned Interventions
Experimental: Verinurad 12 + allopurinol Dose [mg] verinurad/allopurinol: Step 1 - titration_3/100 Step 2 - titration_7.5/200 Step 3 - target dose 12/300	Drug: Verinurad The treatment will be titrated in 3 steps for target low dose (3 mg), intermediate dose (7.5 mg) and high dose (12mg) of verinurad. Drug: Allopurinol The treatment will be titrated in 3 steps. Low dose (100mg), intermediate (200mg) and high dose (300mg) of allopurinol. Other Name: verinurad titration 3 - 7.5 - 12mg Other Name: allopurinol titration 100 - 200 - 300 mg Drug: Allopurinol Study treatments will be titrated in 3 steps: Low dose (100mg), intermediate (200mg) and high dose (300mg) of allopurinol Other Name: allopurinol titration 100 - 200 - 300 mg
Experimental: Allopurinol alone Dose [mg] verinurad/allopurinol: Step 1 - titration_0/100 Step 2 - titration_0/200 Step 3 - target dose 0/300	Drug: Allopurinol Study treatments will be titrated in 3 steps: Low dose (100mg), intermediate (200mg) and high dose (300mg) of allopurinol Other Name: allopurinol titration 100 - 200 - 300 mg
Placebo Comparator: Placebo Placebo [mg] in 3 steps 0/0	Drug: Placebo for verinurad Matching Capsule Other Name: Placebo Drug: Placebo for allopurinol Matching tablet Other Name: Placebo

Documents available

Clinical Study Protocol Redacted
Download
CSR_synopsis_redacted
Download
Statistical Analysis Plan-redacted
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Dalane Kitzman

1326 Riverview Road Ext Lexington, NC 27292-1764 USA

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Clinical Study Protocol Redacted

CSR_synopsis_redacted

Statistical Analysis Plan-redacted

Trial Results Summaries