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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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).

Conditions
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Chronic Kidney Disease + Hyperkalaemia +/- Heart Failure

Intervention / Treatment
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* Drug: Calcium Polystyrene Sulphonate 15g/60 mL water
* Drug: Lokelma® 5 g/45mL water
* Drug: Lokelma® 10 g/45 mL water
* Drug: Veltassa® 8,4 g/80mL water
* Drug: Sodium Polystyrene Sulphonate 15g/60 mL water


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be adults aged ≥18 years, at the time of signing the informed consent. 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.) Prevalent HK with serum K+ >5 mmol/L. Male and/or female 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: Screening serum K+ value which, in the opinion of the investigator, requires immediate medical intervention (ie, cannot wait until after tasting procedures). 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. Known history of drug or alcohol abuse within 6 months of screening. History of QT prolongation associated with other medications that required discontinuation of that medication, including congenital long QT syndrome. Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication are permitted. Have a life expectancy of <6 months. 12-lead ECG with reported QTcF >550 msec at screening. Are current smoker. 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. Participants currently prescribed a K+ binder at time of screening/enrolment. Participants unable to hold other oral medications from 3 hours prior to the start of tasting through 3 hours after the end of tasting. Current participation or participation within the previous 28 days in another clinical study with an investigational product administered. Participants with a known hypersensitivity to Lokelma, Veltassa, or S/CPS or any of the excipients of the NIMPs. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). 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. Previous enrolment or randomisation in the present study. For women only - currently pregnant (confirmed with positive pregnancy test) or breast-feeding. Participants unable to read the local language and therefore unable to complete the questionnaires.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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palatability, Lokelma, hyperkalaemia