Clinical Trials Register

Summary
EudraCT Number:	2018-005030-38
Sponsor's Protocol Code Number:	PAT-CR-302
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2019-10-25
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2018-005030-38

A.3

Full title of the trial

A Multicenter, Double-blind, Placebo-controlled, Randomized Withdrawal, Parallel Group Study of Patiromer for the Management of Hyperkalemia in Subjects Receiving Renin-Angiotensin-Aldosterone System Inhibitor (RAASi) Medications for the Treatment of Heart Failure (DIAMOND)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A placebo controlled Study of Patiromer for the Management of high potassium serum levels in Subjects Receiving a certain group of medications called Renin-Angiotensin-Aldosterone System Inhibitor for treatment of Heart failure.

A.3.2

Name or abbreviated title of the trial where available

DIAMOND

A.4.1

Sponsor's protocol code number

PAT-CR-302

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03888066

A.5.4

Other Identifiers

Name:

IND number

Number:

075615

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Relypsa, Inc., a Vifor Company
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Relypsa, Inc a Vifor Company
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Relypsa, Inc.
B.5.2	Functional name of contact point	Exec. Medical Director
B.5.3	Address:
B.5.3.1	Street Address	100 Cardinal Way
B.5.3.2	Town/ city	Redwood City
B.5.3.3	Post code	94063 (CA)
B.5.3.4	Country	United States
B.5.4	Telephone number	0018447359772
B.5.5	Fax number	0016507796389
B.5.6	E-mail	dgarza@relypsa.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Veltassa®
D.2.1.1.2	Name of the Marketing Authorisation holder	Vifor Fresenius Medical Care Renal Pharma France for Europe and Relypsa, Inc. for USA
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Patiromer
D.3.2	Product code	RLY5016
D.3.4	Pharmaceutical form	Oral suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Patiromer for oral suspension
D.3.9.2	Current sponsor code	RLY5016
D.3.9.3	Other descriptive name	PATIROMER
D.3.9.4	EV Substance Code	SUB182272
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	8.4
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Oral suspension
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Management of hyperkalemia due to renin-angiotension-aldosterone system medications in patients treated for heart failure.

E.1.1.1

Medical condition in easily understood language

Serum potassium levels increase in patients with heart failure.

E.1.1.2

Therapeutic area

Not possible to specify

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	PT
E.1.2	Classification code	10005725
E.1.2	Term	Blood potassium increased
E.1.2	System Organ Class	10022891 - Investigations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To determine if patiromer treatment of subjects who developed hyperkalemia while receiving RAASi medications will result in continued use of RAASi medications in accordance with heart failure (HF) treatment guidelines and thereby decrease the occurrence of the combined endpoint of cardiovascular (CV) death and CV hospitalization events compared with placebo treatment.

E.2.2

Secondary objectives of the trial

Not applicable.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subject provides written informed consent prior to study participation
2. Age at least 18 years or greater
3. History of New York Heart Association (NYHA) Class II–IV HF
4. Left ventricular ejection fraction <40%, measured by any echocardiographic,
radionuclide, or computerized tomography method in the last 12 months without
subsequent measured ejection fraction ≥40% during this interval)
5. Receiving any dose of a beta blocker (BB) for the treatment of HF or unable to
tolerate BB (reason documented)
6.Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 at Screening
(based on a single local laboratory calculation using the Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI) equation; see Section 9.2 of the protocol)
7. Hyperkalemia at Screening (defined by 2 local serum K+ values of >5.0 mEq/L
each obtained from a separate venipuncture, e.g., one in each arm) while receiving ACEi, ARB, ARNi, and/or MRA,
OR
Normokalemia at Screening (serum K+ 4.0–5.0 mEq/L) with a history of hyperkalemia documented by a usual care serum K+ measurement >5.0 mEq/L while on RAASi treatment in the 12 months prior to Screening with a subsequent dose decrease or discontinuation of one or more RAASi medications
8. Females of child-bearing potential must be non-lactating, must have a negative
pregnancy test at Screening, and must agree to continue using contraception (see Section 9.8 of the protocol) throughout the study and for 4 weeks after study completion
9. Hospitalization for HF or equivalent (e.g., urgent emergency room or outpatient visit for worsening HF during which the patient received intravenous medications for the treatment of HF) within last 12 months

E.4

Principal exclusion criteria

1.Current acute decompensated HF. Subjects with a discharge from a hospitalization for acute decompensation of HF at least 4 weeks before Screening
may be included
2. Symptomatic hypotension or systolic blood pressure <90 mmHg
3. Significant primary aortic or mitral valvular heart disease (except mitral
regurgitation due to left ventricular dilatation)
4. Heart transplantation or planned heart transplantation (i.e., currently on a heart transplant list) during the study period
5. Diagnosis of peripartum or chemotherapy-induced cardiomyopathy or acute
myocarditis in the previous 12 months
6. Implantation of a cardiac resynchronization therapy device in the previous
4 weeks
7. Restrictive, constrictive, hypertrophic, or obstructive cardiomyopathy
8. Untreated ventricular arrhythmia with syncope in the previous 4 weeks
9. History of, or current diagnosis of, a severe swallowing disorder, moderate-to-severe gastroparesis, or major gastrointestinal (GI) surgery (e.g., bariatric surgery or large bowel resection)
10. A major CV event within 4 weeks prior to Screening, including acute myocardial infarction, stroke (or transient ischemic attack), a life-threatening atrial or ventricular arrhythmia, or resuscitated cardiac arrest.
11. Brain natriuretic peptide (BNP) <125 pcg/mL or N-terminal pro b-type brain
natriuretic peptide (NT-proBNP) of <500 pcg/mL
12. Liver enzymes (alanine aminotransferase, aspartate aminotransferase) >5 times upper limit of normal at Screening based on the local laboratory
13. Diagnosis or treatment of a malignancy in the past 2 years, excluding
non-melanoma skin cancer and carcinoma in situ of the cervix, or a condition
highly likely to transform into a malignancy during the study
14. Presence of any condition (e.g., drug/alcohol abuse; acute illness), in the opinion of the Investigator, that places the subject at undue risk, or prevents complete participation in the trial procedures, or potentially jeopardizes the quality of the study data
15. Use of any investigational product for an unapproved indication within 1 month prior to Screening or currently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
16. Known hypersensitivity to patiromer (RLY5016) or its components
17. Prior use of commercial patiromer or previous participation in a study assessing patiromer
18. Subjects currently being treated with or having taken any one of the following medications in the 7 days prior to Screening: sodium or calcium polystyrene sulfonate or sodium zirconium cyclosilicate
19. An employee of Relypsa, Vifor Pharma, investigational site or the contract
research organization (CRO)

E.5 End points

E.5.1

Primary end point(s)

Time to first occurrence of CV death or CV hospitalization (or equivalent in outpatient clinic)

E.5.1.1

Timepoint(s) of evaluation of this end point

See endpoint description.

E.5.2

Secondary end point(s)

•Proportion of subjects on ≥50% of guideline-recommended target dose of ACEi,
ARB, or ARNi and ≥50% of guideline-recommended target dose of MRA at the
End of Study (EoS) Visit
• Total HF hospitalizations (or equivalent in outpatient clinic)
• Patient reported outcome: Kansas City Cardiomyopathy Questionnaire (KCCQ)

E.5.2.1

Timepoint(s) of evaluation of this end point

See endpoint description.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Single blind during Run-in phase and double blind during treatment phase

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

156

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Brazil

Bulgaria

Czech Republic

Denmark

France

Georgia

Germany

Israel

Italy

Mexico

Netherlands

Poland

Russian Federation

Serbia

Spain

Sweden

Ukraine

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The study will continue until the required number of composite
endpoint events have occurred.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

1194

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

1194

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

102

F.4.2

For a multinational trial

F.4.2.1

In the EEA

794

F.4.2.2

In the whole clinical trial

2388

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-12-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-01-07

P. End of Trial
P.	End of Trial Status	GB - no longer in EU/EEA

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