Patient Palatability and Preference of 3 Potassium Binders in Patients With Chronic Kidney Disease and Hyperkalaemia (APPETIZE)

Non-Interventional, Exploratory, Phase IV, Single-Blind, Cross-Sectional, Randomised, Cross-over Study Evaluating Patient Palatability and Preference of 3 Potassium Binders in Patients With Chronic Kidney Disease & Hyperkalaemia (APPETIZE).

This non-interventional, Phase IV, exploratory, cross-over, randomised, single-blind, active comparator-controlled study has been designed to measure the palatability and preference of Lokelma® versus Veltassa® versus S/CPS in patients with dialysis and non-dialysis chronic kidney disease (CKD) and hyperkalaemia (HK). The sponsor hypothesizes that palatability, in terms of taste, texture, smell, and mouthfeel, will score higher (better) for Lokelma when compared with Veltassa and S/CPS.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease + Hyperkalaemia +/- Heart Failure
• Intervention / Treatment: Drug: Calcium Polystyrene Sulphonate 15g/60 mL water; Drug: Lokelma® 5 g/45mL water; Drug: Veltassa® 8,4 g/80mL water; Drug: Sodium Polystyrene Sulphonate 15g/60 mL water; Drug: Lokelma® 10 g/45 mL water

Detailed Description

This non-interventional, Phase IV, exploratory, cross-over, randomised, single-blind, active comparator-controlled study has been designed to measure the palatability and preference of sodium zirconium cyclosilicate (hereafter referred to as Lokelma®) versus calcium patiromer sorbitex (hereafter referred to as Veltassa®) versus sodium polystyrene sulphonate (SPS) or calcium polystyrene sulphonate (CPS) (hereafter referred to as S/CPS) in patients with dialysis and non-dialysis chronic kidney disease (CKD) and hyperkalaemia (HK). The sponsor hypothesizes that palatability, in terms of taste, texture, smell, and mouthfeel, will score higher (better) for Lokelma when compared with Veltassa and S/CPS. Each objective will be analysed per country. In addition, the difference in results per regions and overall may be explored.

• Study Type: Observational
• Enrollment (Actual): 147

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1L 3L5
    • Research Site
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Research Site
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Research Site
    • Montreal, Quebec, Canada, H1T 2M4
      • Research Site
• France
  • Amiens, France, 80054
    • Research Site
  • Boulogne Billancourt Cedex, France, 92104
    • Research Site
  • Nice, France, 06000
    • Research Site
• Italy
  • Genova, Italy, 16132
    • Research Site
  • Parma, Italy
    • Research Site
  • Pavia, Italy, 27100
    • Research Site
• Spain
  • Barcelona, Spain, 8035
    • Research Site
  • Córdoba, Spain, 14004
    • Research Site
  • La Coruña, Spain, 15006
    • Research Site
  • Madrid, Spain, 28031
    • Research Site
• Sweden
  • Eskilstuna, Sweden, 631 88
    • Research Site
  • Stockholm, Sweden, 182 88
    • Research Site
• United States
  • Florida
    • Temple Terrace, Florida, United States, 33637
      • Research Site
    • West Palm Beach, Florida, United States, 33411
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 128 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with dialysis and non-dialysis CKD and HK

Description

Inclusion Criteria:

1. Participants must be adults aged ≥18 years, at the time of signing the informed consent.
2. Participants should have CKD defined by having an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 (calculated using CKD-EPI equation) measured twice at least 90 days apart. (The eGFR should be measured when the participant is considered to be in a steady state without recent changes in volume status, medications that could impact the result (eg, nonsteroidal anti-inflammatory drugs, aminoglycosides, co-trimoxazole), or changes in dietary protein intake.)
3. Prevalent HK with serum K+ >5 mmol/L.
4. Male and/or female
5. Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Informed consent must be obtained prior to any study-specific procedures performed.

Exclusion Criteria:

1. Screening serum K+ value which, in the opinion of the investigator, requires immediate medical intervention (ie, cannot wait until after tasting procedures).
2. As judged by the investigator, any evidence of any condition which in the investigator's opinion makes it undesirable for the participant to participate in the study.
3. Known history of drug or alcohol abuse within 6 months of screening.
4. History of QT prolongation associated with other medications that required discontinuation of that medication, including congenital long QT syndrome.
5. Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication are permitted.
6. Have a life expectancy of <6 months.
7. 12-lead ECG with reported QTcF >550 msec at screening.
8. Are current smoker.
9. Have mouth ulcers/mouth infection, respiratory infection, nasal congestion, or other condition, medication, or procedure which may interfere with sense of smell or taste, in opinion of the investigator.
10. Participants currently prescribed a K+ binder at time of screening/enrolment.
11. Participants unable to hold other oral medications from 3 hours prior to the start of tasting through 3 hours after the end of tasting.
12. Current participation or participation within the previous 28 days in another clinical study with an investigational product administered.
13. Participants with a known hypersensitivity to Lokelma, Veltassa, or S/CPS or any of the excipients of the NIMPs.
14. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
15. Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements.
16. Previous enrolment or randomisation in the present study.
17. For women only - currently pregnant (confirmed with positive pregnancy test) or breast-feeding.
18. Participants unable to read the local language and therefore unable to complete the questionnaires.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
dialysis-dependent; chronic kidney disease patients with hyperkalaemia and dialysis-dependent	Drug: Calcium Polystyrene Sulphonate 15g/60 mL water; K+ binder, not for treatment but for tasting (sip-and-spit taste test); Drug: Lokelma® 5 g/45mL water; K+ binder, not for treatment but for tasting (sip-and-spit taste test); Drug: Veltassa® 8,4 g/80mL water; K+ binder, not for treatment but for tasting (sip-and-spit taste test); Drug: Sodium Polystyrene Sulphonate 15g/60 mL water; K+ binder, not for treatment but for tasting (sip-and-spit taste test)
non-dialysis-dependent; chronic kidney disease patients with hyperkalaemia and non-dialysis-dependent	Drug: Calcium Polystyrene Sulphonate 15g/60 mL water; K+ binder, not for treatment but for tasting (sip-and-spit taste test); Drug: Veltassa® 8,4 g/80mL water; K+ binder, not for treatment but for tasting (sip-and-spit taste test); Drug: Sodium Polystyrene Sulphonate 15g/60 mL water; K+ binder, not for treatment but for tasting (sip-and-spit taste test); Drug: Lokelma® 10 g/45 mL water; K+ binder, not for treatment but for tasting (sip-and-spit taste test)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in scores (0-40) for overall palatability of NIMPs	To compare patient-reported overall palatability (composite of taste, texture, smell, and mouthfeel) between Lokelma and Veltassa, and between Lokelma and S/CPS in the United States (US)	Tasting visit (day 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in scores (0-40) for overall palatability of NIMPs	To compare patient-reported overall palatability (composite of taste, texture, smell, and mouthfeel) between Lokelma and Veltassa, and between Lokelma and S/CPS in Canada	Tasting visit (day 1)
Difference in scores (0-40) for overall palatability of NIMPs	To compare patient-reported overall palatability (composite of taste, texture, smell, and mouthfeel) between Lokelma and Veltassa, and between Lokelma and S/CPS in the European Union (EU)	Tasting visit (day 1)
Difference in scores for feelings of Appeal (4-36), Engagement (4-36), and Empowerment (4-36) regarding taste overall palatability of NIMPs using the AdSAM emotional response tool	To compare patient-reported emotional response to overall palatability (composite of taste, texture, smell, and mouthfeel) taste between Lokelma and Veltassa, and between Lokelma and S/CPS in the US	Tasting visit (day 1)
Difference in scores for feelings of appeal (4-36), engagement (4-36), and empowerment (4-36) regarding overall palatability of NIMPs using the AdSAM emotional response tool	To compare patient-reported emotional response to overall palatability (composite of taste, texture, smell, and mouthfeel) between Lokelma and Veltassa, and between Lokelma and S/CPS in Canada	Tasting visit (day 1)
Difference in scores for feelings of appeal (4-36), engagement (4-36), and empowerment (4-36) regarding overall palatability of NIMPs using the AdSAM emotional response tool	To compare patient-reported emotional response to overall palatability (composite of taste, texture, smell, and mouthfeel) between Lokelma and Veltassa, and ,between Lokelma and S/CPS in the EU	Tasting visit (day 1)
Scoring of palatability (0-40), Appeal of palatability (4-36), Engagement of palatability (4-36), Empowerment of palatability (4-36), Overall composite emotional strength indicator scores (0-1200), Feelings towards palatability	To describe patient-reported preference for overall palatability (composite of taste, texture, smell, and mouthfeel) (scoring and non-verbal emotional response for how each NIMP made patients feel ofto each NIMP) of 3 currently marketed K+ binders ((of Lokelma, Veltassa, and S/CPS) in the US, Canada, and EU, respectively)	Tasting Visit (day 1)
Scoring (0-10), Appeal (9-1), Engagement (9-1), Empowerment (1-9), Overall emotional strength indicator score (0-300), and Feelings towards willingness to take a K+ binder	To describe and compare, based on the overall palatability experience, scoring and emotional response for how willing patients would be to take each K+ binder to help manage their serum potassium (likelihood of adherence) in the US, Canada, and EU	Tasting Visit (day 1)
Overall preference ranking of NIMPs (1, 2, or 3) of Lokelma, Veltassa, and S/CPS • Use of Comparative AdSAM Emotional Strength Index and Emotional TempIndicator scores to derive overall preference	To describe patient-reported preference by ranking the NIMPs, and derived preference based on the emotional strength indexindicator scores in the US, Canada, and EU	Tasting visit (day 1)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
See primary and secondary endpoints	Overall palatability scores (0-40) between Lokelma and Veltassa, and between Lokelma and S/CPS will be described and compared for all primary and secondary endpoints for: North America, per individual EU countries (where data permit), and over all countries/regions	Tasting visit (day 1)
See primary and secondary endpoints	Patient preference between Lokelma and Veltassa, and between Lokelma and S/CPS will be described and compared for all primary and secondary endpoints for: North America, per individual EU countries (where data permit), and over all countries/regions.	Tasting visit (day 1)
Categories or combinations based on Appeal of each attribute (taste, texture, smell, and mouthfeel)	Appeal test score (1-9) for each attribute (taste, texture, smell, and mouthfeel) will be measured using AdSAM questionnaires using published research and analysed using AdSAM methodology and compare between Lokelma and Veltassa, and between Lokelma and S/CPS for the US, Canada, EU, North America, per individual EU countries (where data permit), and over all countries/regions.	Tasting visit (day 1)
Categories or combinations based on Engagement of each attribute (taste, texture, smell, and mouthfeel)	Engagement test score (1-9) for each attribute (taste, texture, smell, and mouthfeel) will be measured using AdSAM questionnaires team using published research and analysed using AdSAM methodology and compare between Lokelma and Veltassa, and between Lokelma and S/CPS for the US, Canada, EU, North America, per individual EU countries (where data permit), and over all countries/regions	Tasting visit (day 1)
Categories or combinations based on Empowerment of each attribute (taste, texture, smell, and mouthfeel)	Empowerment test score (1-9) for each attribute (taste, texture, smell, and mouthfeel) will be measured using AdSAM questionnaires team using published research and analysed using AdSAM methodology and compare between Lokelma and Veltassa, and between Lokelma and S/CPS for the US, Canada, EU, North America, per individual EU countries (where data permit), and over all countries/regions	Tasting visit (day 1)
Scoring (0-10) of taste, texture, smell, and mouthfeel	Scores of individual palatability attributes (taste, texture, smell, and mouthfeel) will be described individually by countries/regions	Tasting visit (day 1)
Determining specific feelings regarding taste, texture, smell, and mouthfeel using the AdSAM emotional response model	Emotional response of individual palatability attributes (taste, texture, smell, and mouthfeel) will be described individually by countries/regions	Tasting visit (day 1)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Medidata Solutions; ERT: Clinical Trial Technology Solutions; Calyx; Labcorp Corporation of America Holdings, Inc
• Investigators: Study Director: Eric Wittbrodt, PharmD, MPH, AstraZeneca, Biopharmaceuticals Medical

Publications and helpful links

General Publications

• Thomsen RW, Nicolaisen SK, Hasvold P, Sanchez RG, Pedersen L, Adelborg K, Egstrup K, Egfjord M, Sorensen HT. Elevated potassium levels in patients with chronic kidney disease: occurrence, risk factors and clinical outcomes-a Danish population-based cohort study. Nephrol Dial Transplant. 2018 Sep 1;33(9):1610-1620. doi: 10.1093/ndt/gfx312.
• Laureati P, Xu Y, Trevisan M, Schalin L, Mariani I, Bellocco R, Sood MM, Barany P, Sjolander A, Evans M, Carrero JJ. Initiation of sodium polystyrene sulphonate and the risk of gastrointestinal adverse events in advanced chronic kidney disease: a nationwide study. Nephrol Dial Transplant. 2020 Sep 1;35(9):1518-1526. doi: 10.1093/ndt/gfz150.
• Noel JA, Bota SE, Petrcich W, Garg AX, Carrero JJ, Harel Z, Tangri N, Clark EG, Komenda P, Sood MM. Risk of Hospitalization for Serious Adverse Gastrointestinal Events Associated With Sodium Polystyrene Sulfonate Use in Patients of Advanced Age. JAMA Intern Med. 2019 Aug 1;179(8):1025-1033. doi: 10.1001/jamainternmed.2019.0631. Erratum In: JAMA Intern Med. 2020 Feb 24;:
• Zann V, McDermott J, Jacobs JW, Davidson JP, Lin F, Korner P, Blanks RC, Rosenbaum DP. Palatability and physical properties of potassium-binding resin RDX7675: comparison with sodium polystyrene sulfonate. Drug Des Devel Ther. 2017 Sep 6;11:2663-2673. doi: 10.2147/DDDT.S143461. eCollection 2017.

Helpful Links

• AdSAM Emotional Response Modelling website. AdSAM Measure.
• Gasparini A, Evans M, Barany P, Xu H, Jernberg T, Ärnlöv J, et al. Plasma potassium ranges associated with mortality across stages of chronic kidney disease: the Stockholm CREAtinine Measurements (SCREAM) project. Nephrol Dial Transplant. 2018;(Aug):1-8.
• Stokes JR, Boehm MW, Baier SK. Oral processing, texture and mouthfeel: From rheology to tribology and beyond. Curr Opin Colloid Interface Sci [Internet]. 2013;18(4):349-59.
• Guinard JX, Mazzucchelli R. The sensory perception of texture and mouthfeel. Trends Food Sci Technol. 1996;7(7):213-9
• Morris JD, Woo C, Geason JA, and Kim J. The power of affect: predicting intention. Journal of Advertising Research. 2002;42(3):7-17.
• CSR synopsis redacted

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2020
• Primary Completion (Actual): January 12, 2022
• Study Completion (Actual): January 12, 2022

Study Registration Dates

• First Submitted: July 31, 2020
• First Submitted That Met QC Criteria: September 25, 2020
• First Posted (Actual): September 28, 2020

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 6, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: palatability; Lokelma; hyperkalaemia
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Water-Electrolyte Imbalance; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Hyperkalemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Chelating Agents; Sequestering Agents; Calcium; Polystyrene sulfonic acid
• Other Study ID Numbers: D9480C00016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

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: 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.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No