Trial Outcomes & Findings for Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients With Symptomatic HFrEF Receiving Spironolactone (NCT NCT04676646)

Last Updated: 2025-07-09

Results Overview

The median percentages of participants having a response are presented. Response means all three requirements were met. Non-response was indicated for participants lost to follow-up, including death. The treatment effect was analysed using a generalised estimating equation (GEE) model with a binomial family and a log link, a dependent variable of response per visit, fixed independent variables of randomised treatment, subject recruitment country, a per visit indicator variable and open-label period cohort. The common odds ratio was derived together with two-sided 95% confidence intervals.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

366 participants

Primary outcome timeframe

From Month 1 (Visit 9) to Month 6 (Visit 14), up to 6 months

Results posted on

2025-07-09

Participant Flow

This study consisted of two phases, an open-label run-in phase and a placebo-controlled randomized-withdrawal phase. Of the 366 participants enrolled in the open-label run-in phase, 203 participants entered into the randomized-withdrawal phase (102 received SZC treatment and 101 received placebo).

Participant milestones

Participant milestones
Measure	Open-label Run-in Phase Participants with symptomatic heart failure with reduced ejection fraction who were taking no or low-dose spironolactone or eplerenone (\< 25 mg daily) at screening were enrolled and allocated to Cohort 1 (hyperkalaemic at study entry) or Cohort 2 (normokalaemic at study entry).	Randomized-withdrawal Phase - SZC Group Participants continued on the SZC and spironolactone dose they were receiving at the end of the run-in phase.	Randomized-withdrawal Phase - Placebo Group Participants continued on the placebo and spironolactone dose they were receiving at the end of the run-in phase.
Open-label Run-in Phase STARTED	366	0	0
Open-label Run-in Phase COMPLETED	203	0	0
Open-label Run-in Phase NOT COMPLETED	163	0	0
Randomised-withdrawal Phase STARTED	0	102	101
Randomised-withdrawal Phase COMPLETED	0	88	87
Randomised-withdrawal Phase NOT COMPLETED	0	14	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Open-label Run-in Phase Participants with symptomatic heart failure with reduced ejection fraction who were taking no or low-dose spironolactone or eplerenone (\< 25 mg daily) at screening were enrolled and allocated to Cohort 1 (hyperkalaemic at study entry) or Cohort 2 (normokalaemic at study entry).	Randomized-withdrawal Phase - SZC Group Participants continued on the SZC and spironolactone dose they were receiving at the end of the run-in phase.	Randomized-withdrawal Phase - Placebo Group Participants continued on the placebo and spironolactone dose they were receiving at the end of the run-in phase.
Open-label Run-in Phase Adverse Event	3	0	0
Open-label Run-in Phase Death	3	0	0
Open-label Run-in Phase Study-specific Withdrawal Criteria	2	0	0
Open-label Run-in Phase Failure to Meet Randomization Criteria	144	0	0
Open-label Run-in Phase Lost to Follow-up	1	0	0
Open-label Run-in Phase Withdrawal by Subject	8	0	0
Open-label Run-in Phase Withdrawn from study due to withdrawal by co-investigator	1	0	0
Open-label Run-in Phase Withdrawn from study due to withdrawal by PI	1	0	0
Randomised-withdrawal Phase Adverse Event	0	5	5
Randomised-withdrawal Phase Death	0	1	2
Randomised-withdrawal Phase Development of Study-specific Withdrawal Criteria	0	2	4
Randomised-withdrawal Phase Lost to Follow-up	0	1	0
Randomised-withdrawal Phase Withdrawn from study due to PD - Wrong doses of spironolactone	0	1	0
Randomised-withdrawal Phase Withdrawn from study due to spironolactone was stopped on May 28, related hyperkalaemia	0	1	0
Randomised-withdrawal Phase Withdrawn from study due to the participant did not have enough medication by issues in IWRS	0	0	1
Randomised-withdrawal Phase Withdrawn from study due to the patient was random by mistake on this date he was an OLRIF	0	1	0
Randomised-withdrawal Phase Withdrawal by Subject	0	2	2

Baseline Characteristics

Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients With Symptomatic HFrEF Receiving Spironolactone

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Randomized-withdrawal Phase - SZC Group n=102 Participants Participants continued on the SZC and spironolactone dose they were receiving at the end of the run-in phase.	Randomized-withdrawal Phase - Placebo Group n=101 Participants Participants continued on the placebo and spironolactone dose they were receiving at the end of the run-in phase.	Total n=203 Participants Total of all reporting groups
Age, Continuous	72.5 Years STANDARD_DEVIATION 7.88 • n=5 Participants	69.2 Years STANDARD_DEVIATION 10.46 • n=7 Participants	70.9 Years STANDARD_DEVIATION 9.39 • n=5 Participants
Age, Customized 18-64 years	18 Participants n=5 Participants	32 Participants n=7 Participants	50 Participants n=5 Participants
Age, Customized 65-84 years	79 Participants n=5 Participants	63 Participants n=7 Participants	142 Participants n=5 Participants
Age, Customized >=85 years	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	26 Participants n=7 Participants	52 Participants n=5 Participants
Sex: Female, Male Male	76 Participants n=5 Participants	75 Participants n=7 Participants	151 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	40 Participants n=5 Participants	27 Participants n=7 Participants	67 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	62 Participants n=5 Participants	74 Participants n=7 Participants	136 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	91 Participants n=5 Participants	94 Participants n=7 Participants	185 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Country BRA	31 Participants n=5 Participants	19 Participants n=7 Participants	50 Participants n=5 Participants
Country CAN	7 Participants n=5 Participants	16 Participants n=7 Participants	23 Participants n=5 Participants
Country CZE	3 Participants n=5 Participants	13 Participants n=7 Participants	16 Participants n=5 Participants
Country ESP	33 Participants n=5 Participants	26 Participants n=7 Participants	59 Participants n=5 Participants
Country GBR	9 Participants n=5 Participants	4 Participants n=7 Participants	13 Participants n=5 Participants
Country HUN	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Country POL	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Country USA	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Type 2 diabetes at baseline Yes	27 Participants n=5 Participants	25 Participants n=7 Participants	52 Participants n=5 Participants
Type 2 diabetes at baseline No	75 Participants n=5 Participants	76 Participants n=7 Participants	151 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Month 1 (Visit 9) to Month 6 (Visit 14), up to 6 months

Population: Full Analysis Set

Outcome measures

Outcome measures
Measure	Randomized-withdrawal Phase - SZC Group n=102 Participants Participants continued on the SZC and spironolactone dose they were receiving at the end of the run-in phase.	Randomized-withdrawal Phase - Placebo Group n=101 Participants Participants continued on the placebo and spironolactone dose they were receiving at the end of the run-in phase.
Participants Who Achieved Response, Defined as Serum Potassium (sK+) Within 3.5 to 5.0 mEq/L, Spironolactone Greater Than or Equal to 25 mg Daily, no Rescue Therapy for Hyperkalaemia	72.1 Percentage of participants	35.7 Percentage of participants

SECONDARY outcome

Timeframe: From Month 1 (Visit 9) to Month 6 (Visit 14), up to 6 months

Population: Full Analysis Set

The median percentages of participants who achieved a response are presented. Response means all three requirements were met. Non-response was indicated for participants lost to follow-up, including death. The analysis was performed using a GEE model with a binomial family and a log link, a dependent variable of response per visit, fixed independent variables of randomised treatment, subject recruitment country, a per visit indicator variable and open-label period cohort. The common odds ratio was derived together with two-sided 95% confidence intervals.

Outcome measures

Outcome measures
Measure	Randomized-withdrawal Phase - SZC Group n=102 Participants Participants continued on the SZC and spironolactone dose they were receiving at the end of the run-in phase.	Randomized-withdrawal Phase - Placebo Group n=101 Participants Participants continued on the placebo and spironolactone dose they were receiving at the end of the run-in phase.
Participants Who Achieved Response, Defined as sK+ Within 3.5-5.0 mEq/L, on the Same Dose of Spironolactone as Randomisation, no Rescue Therapy for Hyperkalaemia	58.2 Percentage of participants	22.9 Percentage of participants

SECONDARY outcome

Timeframe: From Month 1 (Visit 9) to Month 6 (Visit 14), up to 6 months

Population: Full Analysis Set

The median percentages of participants who achieved a response are presented. Response means that the requirement was met. Non-response was indicated for subjects lost to follow-up, including death. The analysis was performed using a GEE model with a binomial family and a log link, a dependent variable of response per visit, fixed independent variables of randomised treatment, subject recruitment country, a per visit indicator variable and open-label period cohort. The common odds ratio was derived together with two-sided 95% confidence intervals.

Outcome measures

Outcome measures
Measure	Randomized-withdrawal Phase - SZC Group n=102 Participants Participants continued on the SZC and spironolactone dose they were receiving at the end of the run-in phase.	Randomized-withdrawal Phase - Placebo Group n=101 Participants Participants continued on the placebo and spironolactone dose they were receiving at the end of the run-in phase.
Participants Who Achieved Response, Defined as Spironolactone Greater Than or Equal to 25 mg Daily	81.4 Percentage of participants	49.5 Percentage of participants

SECONDARY outcome

Timeframe: From randomisation to the end of treatment (EOT) visit, up to 6 months

Population: Full Analysis Set

The time to first hyperkalaemia episode for participants on SZC compared to placebo during the randomised-withdrawal period, with hyperkalaemia defined as sK+ greater than 5.0 mEq/L as assessed by central laboratory, is presented in median time (days). The analysis was performed using a Cox regression model including randomised treatment group and subject recruitment country, adjusted for the stratification factor (hyperkalaemia vs normokalaemia at study entry). Placebo group used as reference level in Cox model.

Outcome measures

Outcome measures
Measure	Randomized-withdrawal Phase - SZC Group n=102 Participants Participants continued on the SZC and spironolactone dose they were receiving at the end of the run-in phase.	Randomized-withdrawal Phase - Placebo Group n=101 Participants Participants continued on the placebo and spironolactone dose they were receiving at the end of the run-in phase.
Time to First Hyperkalaemia (sK+ Greater Than 5.0mEq/L) Episode	65.0 Days Interval 35.0 to 98.0	9.0 Days Interval 8.0 to 13.0

SECONDARY outcome

Timeframe: From randomisation to the EOT visit, up to 6 months

Population: Full Analysis Set

The time to first instance of decrease or discontinuation of spironolactone dose due to hyperkalaemia is presented in median time (days). The analysis was performed using a Cox regression model, adjusted for the stratification factor (hyperkalaemia vs normokalaemia at study entry).

Outcome measures

Outcome measures
Measure	Randomized-withdrawal Phase - SZC Group n=102 Participants Participants continued on the SZC and spironolactone dose they were receiving at the end of the run-in phase.	Randomized-withdrawal Phase - Placebo Group n=101 Participants Participants continued on the placebo and spironolactone dose they were receiving at the end of the run-in phase.
Time to First Instance of Decrease or Discontinuation of Spironolactone Dose Due to Hyperkalaemia	NA Days Median time to first event could not be calculated due to the low number of events.	NA Days Median time to first event could not be calculated due to the low number of events.

SECONDARY outcome

Timeframe: At EOT visit (approximately 6 months post-randomisation)

Population: Full Analysis Set: all participants with more than 50% of responses available at a visit.

The KCCQ is a 23-item instrument measuring, from the patients' perspectives, their heart failure-related symptoms, physical and social limitations, self-efficacy, and health-related quality of life (QoL) over the prior 2 weeks. It was scored as follows: Physical Limitation (items 1a-f), Symptom Stability (item 2), Symptom Frequency (items 3, 5, 7, and 9), Symptom Burden (items 4, 6, and 8), Self Efficacy (items 10 and 11), QoL (items 12, 13, and 14), and Social Limitation (items 15a-d). Scores were calculated by summing the responses within each domain and by taking the average. Scale scores were transformed to a 0 to 100 range, with 0 implying the lowest level of functioning and 100 for the highest level of functioning. The CSS was calculated as the average of Physical Limitation Score and Total Symptom Score (TSS) and the TSS was calculated as the average of Symptom Frequency and Symptom Burden Scores. The change from randomisation in KCCQ-CSS is reported.

Outcome measures

Outcome measures
Measure	Randomized-withdrawal Phase - SZC Group n=72 Participants Participants continued on the SZC and spironolactone dose they were receiving at the end of the run-in phase.	Randomized-withdrawal Phase - Placebo Group n=59 Participants Participants continued on the placebo and spironolactone dose they were receiving at the end of the run-in phase.
Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) at EOT	71.27 Score on a scale Standard Error 2.57	72.27 Score on a scale Standard Error 2.36

OTHER_PRE_SPECIFIED outcome

Timeframe: During the randomised-withdrawal period and up to 14 days after discontinuation of SZC or placebo, up to 6.5 months

Population: Safety Set Randomised

The location and severity of peripheral oedema that occurred during the randomised-withdrawal phase are presented. Participants with multiple peripheral oedema events were counted only once. The location of oedema is not mutually exclusive so multiple locations may apply for each participant.

Outcome measures

Outcome measures
Measure	Randomized-withdrawal Phase - SZC Group n=22 Participants Participants continued on the SZC and spironolactone dose they were receiving at the end of the run-in phase.	Randomized-withdrawal Phase - Placebo Group n=16 Participants Participants continued on the placebo and spironolactone dose they were receiving at the end of the run-in phase.
Location and Severity of Peripheral Oedema Location of oedema: pedal oedema	13 Participants	10 Participants
Location and Severity of Peripheral Oedema Location of oedema: ankle oedema	17 Participants	13 Participants
Location and Severity of Peripheral Oedema Location of oedema: pretibial oedema	11 Participants	5 Participants
Location and Severity of Peripheral Oedema Location of oedema: thigh oedema	1 Participants	0 Participants
Location and Severity of Peripheral Oedema Severity of pedal oedema - right side: trace	4 Participants	3 Participants
Location and Severity of Peripheral Oedema Severity of pedal oedema - right side: mild	1 Participants	5 Participants
Location and Severity of Peripheral Oedema Severity of pedal oedema - right side: moderate	7 Participants	1 Participants
Location and Severity of Peripheral Oedema Severity of pedal oedema - right side: severe	0 Participants	0 Participants
Location and Severity of Peripheral Oedema Severity of pedal oedema - left side: trace	4 Participants	5 Participants
Location and Severity of Peripheral Oedema Severity of pedal oedema - left side: mild	2 Participants	4 Participants
Location and Severity of Peripheral Oedema Severity of pedal oedema - left side: moderate	7 Participants	1 Participants
Location and Severity of Peripheral Oedema Severity of pedal oedema - left side: severe	0 Participants	0 Participants
Location and Severity of Peripheral Oedema Severity of ankle oedema - right side: trace	4 Participants	4 Participants
Location and Severity of Peripheral Oedema Severity of ankle oedema - right side: mild	5 Participants	6 Participants
Location and Severity of Peripheral Oedema Severity of ankle oedema - right side: moderate	7 Participants	1 Participants
Location and Severity of Peripheral Oedema Severity of ankle oedema - right side: severe	0 Participants	0 Participants
Location and Severity of Peripheral Oedema Severity of ankle oedema - left side: trace	4 Participants	6 Participants
Location and Severity of Peripheral Oedema Severity of ankle oedema - left side: mild	5 Participants	6 Participants
Location and Severity of Peripheral Oedema Severity of ankle oedema - left side: moderate	8 Participants	1 Participants
Location and Severity of Peripheral Oedema Severity of ankle oedema - left side: severe	0 Participants	0 Participants
Location and Severity of Peripheral Oedema Severity of pretibial edema - right side: trace	2 Participants	1 Participants
Location and Severity of Peripheral Oedema Severity of pretibial edema - right side: mild	4 Participants	2 Participants
Location and Severity of Peripheral Oedema Severity of pretibial edema - right side: moderate	5 Participants	1 Participants
Location and Severity of Peripheral Oedema Severity of pretibial edema - right side: severe	0 Participants	0 Participants
Location and Severity of Peripheral Oedema Severity of pretibial edema - left side: trace	1 Participants	2 Participants
Location and Severity of Peripheral Oedema Severity of pretibial edema - left side: mild	3 Participants	2 Participants
Location and Severity of Peripheral Oedema Severity of pretibial edema - left side: moderate	7 Participants	1 Participants
Location and Severity of Peripheral Oedema Severity of pretibial edema - left side: severe	0 Participants	0 Participants
Location and Severity of Peripheral Oedema Severity of thigh edema - right side: trace	0 Participants	0 Participants
Location and Severity of Peripheral Oedema Severity of thigh edema - right side: mild	0 Participants	0 Participants
Location and Severity of Peripheral Oedema Severity of thigh edema - right side: moderate	1 Participants	0 Participants
Location and Severity of Peripheral Oedema Severity of thigh edema - right side: severe	0 Participants	0 Participants
Location and Severity of Peripheral Oedema Severity of thigh edema - left side: trace	0 Participants	0 Participants
Location and Severity of Peripheral Oedema Severity of thigh edema - left side: mild	0 Participants	0 Participants
Location and Severity of Peripheral Oedema Severity of thigh edema - left side: moderate	1 Participants	0 Participants
Location and Severity of Peripheral Oedema Severity of thigh edema - left side: severe	0 Participants	0 Participants

Adverse Events

Open-label Run-in Phase

Serious events: 11 serious events

Other events: 9 other events

Deaths: 7 deaths

Randomized-withdrawal Phase - SZC Group

Serious events: 23 serious events

Other events: 20 other events

Deaths: 2 deaths

Randomized-withdrawal Phase - Placebo Group

Serious events: 22 serious events

Other events: 25 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Open-label Run-in Phase n=362 participants at risk Participants with symptomatic heart failure with reduced ejection fraction who were taking no or low-dose spironolactone or eplerenone (\<25 mg daily) at screening were enrolled and allocated to Cohort 1 (hyperkalaemic at study entry) or Cohort 2 (normokalaemic at study entry).	Randomized-withdrawal Phase - SZC Group n=101 participants at risk Participants continued on the SZC and spironolactone dose they were receiving at the end of the run-in phase.	Randomized-withdrawal Phase - Placebo Group n=101 participants at risk Participants continued on the placebo and spironolactone dose they were receiving at the end of the run-in phase.
General disorders Oedema peripheral	0.83% 3/362 • Number of events 3 • Open-label Run-in Phase (OLP): includes treatment-emergent adverse events (TEAEs) that occurred during the OLP and all AEs which occurred prior to first dose of SZC which worsen in severity following dosing during the OLP, up to 4-6 weeks Randomised-withdrawal Phase (RWP): includes TEAEs that occurred during the RWP and up to 14 days after discontinuation of SZC/placebo and all AEs which occurred prior to first dose which worsen in severity following dosing during the RWP, up to 6.5 months The AEs that occurred during the OLP and RWP are reported. The SZC group and Placebo group represent participants assessed during the RWP. OLP: Of the 366 participants who enrolled, 4 participants did not receive treatment and were excluded from the analysis. RWP: Of the 203 participants randomized (102 in the SZC group and 101 in the Placebo group), 1 participant from the SZC group did not receive treatment and was excluded from the analysis.	5.9% 6/101 • Number of events 6 • Open-label Run-in Phase (OLP): includes treatment-emergent adverse events (TEAEs) that occurred during the OLP and all AEs which occurred prior to first dose of SZC which worsen in severity following dosing during the OLP, up to 4-6 weeks Randomised-withdrawal Phase (RWP): includes TEAEs that occurred during the RWP and up to 14 days after discontinuation of SZC/placebo and all AEs which occurred prior to first dose which worsen in severity following dosing during the RWP, up to 6.5 months The AEs that occurred during the OLP and RWP are reported. The SZC group and Placebo group represent participants assessed during the RWP. OLP: Of the 366 participants who enrolled, 4 participants did not receive treatment and were excluded from the analysis. RWP: Of the 203 participants randomized (102 in the SZC group and 101 in the Placebo group), 1 participant from the SZC group did not receive treatment and was excluded from the analysis.	2.0% 2/101 • Number of events 2 • Open-label Run-in Phase (OLP): includes treatment-emergent adverse events (TEAEs) that occurred during the OLP and all AEs which occurred prior to first dose of SZC which worsen in severity following dosing during the OLP, up to 4-6 weeks Randomised-withdrawal Phase (RWP): includes TEAEs that occurred during the RWP and up to 14 days after discontinuation of SZC/placebo and all AEs which occurred prior to first dose which worsen in severity following dosing during the RWP, up to 6.5 months The AEs that occurred during the OLP and RWP are reported. The SZC group and Placebo group represent participants assessed during the RWP. OLP: Of the 366 participants who enrolled, 4 participants did not receive treatment and were excluded from the analysis. RWP: Of the 203 participants randomized (102 in the SZC group and 101 in the Placebo group), 1 participant from the SZC group did not receive treatment and was excluded from the analysis.
Metabolism and nutrition disorders Hyperkalaemia	1.7% 6/362 • Number of events 9 • Open-label Run-in Phase (OLP): includes treatment-emergent adverse events (TEAEs) that occurred during the OLP and all AEs which occurred prior to first dose of SZC which worsen in severity following dosing during the OLP, up to 4-6 weeks Randomised-withdrawal Phase (RWP): includes TEAEs that occurred during the RWP and up to 14 days after discontinuation of SZC/placebo and all AEs which occurred prior to first dose which worsen in severity following dosing during the RWP, up to 6.5 months The AEs that occurred during the OLP and RWP are reported. The SZC group and Placebo group represent participants assessed during the RWP. OLP: Of the 366 participants who enrolled, 4 participants did not receive treatment and were excluded from the analysis. RWP: Of the 203 participants randomized (102 in the SZC group and 101 in the Placebo group), 1 participant from the SZC group did not receive treatment and was excluded from the analysis.	11.9% 12/101 • Number of events 16 • Open-label Run-in Phase (OLP): includes treatment-emergent adverse events (TEAEs) that occurred during the OLP and all AEs which occurred prior to first dose of SZC which worsen in severity following dosing during the OLP, up to 4-6 weeks Randomised-withdrawal Phase (RWP): includes TEAEs that occurred during the RWP and up to 14 days after discontinuation of SZC/placebo and all AEs which occurred prior to first dose which worsen in severity following dosing during the RWP, up to 6.5 months The AEs that occurred during the OLP and RWP are reported. The SZC group and Placebo group represent participants assessed during the RWP. OLP: Of the 366 participants who enrolled, 4 participants did not receive treatment and were excluded from the analysis. RWP: Of the 203 participants randomized (102 in the SZC group and 101 in the Placebo group), 1 participant from the SZC group did not receive treatment and was excluded from the analysis.	22.8% 23/101 • Number of events 34 • Open-label Run-in Phase (OLP): includes treatment-emergent adverse events (TEAEs) that occurred during the OLP and all AEs which occurred prior to first dose of SZC which worsen in severity following dosing during the OLP, up to 4-6 weeks Randomised-withdrawal Phase (RWP): includes TEAEs that occurred during the RWP and up to 14 days after discontinuation of SZC/placebo and all AEs which occurred prior to first dose which worsen in severity following dosing during the RWP, up to 6.5 months The AEs that occurred during the OLP and RWP are reported. The SZC group and Placebo group represent participants assessed during the RWP. OLP: Of the 366 participants who enrolled, 4 participants did not receive treatment and were excluded from the analysis. RWP: Of the 203 participants randomized (102 in the SZC group and 101 in the Placebo group), 1 participant from the SZC group did not receive treatment and was excluded from the analysis.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/362 • Open-label Run-in Phase (OLP): includes treatment-emergent adverse events (TEAEs) that occurred during the OLP and all AEs which occurred prior to first dose of SZC which worsen in severity following dosing during the OLP, up to 4-6 weeks Randomised-withdrawal Phase (RWP): includes TEAEs that occurred during the RWP and up to 14 days after discontinuation of SZC/placebo and all AEs which occurred prior to first dose which worsen in severity following dosing during the RWP, up to 6.5 months The AEs that occurred during the OLP and RWP are reported. The SZC group and Placebo group represent participants assessed during the RWP. OLP: Of the 366 participants who enrolled, 4 participants did not receive treatment and were excluded from the analysis. RWP: Of the 203 participants randomized (102 in the SZC group and 101 in the Placebo group), 1 participant from the SZC group did not receive treatment and was excluded from the analysis.	5.9% 6/101 • Number of events 6 • Open-label Run-in Phase (OLP): includes treatment-emergent adverse events (TEAEs) that occurred during the OLP and all AEs which occurred prior to first dose of SZC which worsen in severity following dosing during the OLP, up to 4-6 weeks Randomised-withdrawal Phase (RWP): includes TEAEs that occurred during the RWP and up to 14 days after discontinuation of SZC/placebo and all AEs which occurred prior to first dose which worsen in severity following dosing during the RWP, up to 6.5 months The AEs that occurred during the OLP and RWP are reported. The SZC group and Placebo group represent participants assessed during the RWP. OLP: Of the 366 participants who enrolled, 4 participants did not receive treatment and were excluded from the analysis. RWP: Of the 203 participants randomized (102 in the SZC group and 101 in the Placebo group), 1 participant from the SZC group did not receive treatment and was excluded from the analysis.	0.00% 0/101 • Open-label Run-in Phase (OLP): includes treatment-emergent adverse events (TEAEs) that occurred during the OLP and all AEs which occurred prior to first dose of SZC which worsen in severity following dosing during the OLP, up to 4-6 weeks Randomised-withdrawal Phase (RWP): includes TEAEs that occurred during the RWP and up to 14 days after discontinuation of SZC/placebo and all AEs which occurred prior to first dose which worsen in severity following dosing during the RWP, up to 6.5 months The AEs that occurred during the OLP and RWP are reported. The SZC group and Placebo group represent participants assessed during the RWP. OLP: Of the 366 participants who enrolled, 4 participants did not receive treatment and were excluded from the analysis. RWP: Of the 203 participants randomized (102 in the SZC group and 101 in the Placebo group), 1 participant from the SZC group did not receive treatment and was excluded from the analysis.

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 18772409479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Investigator shall be entitled to publish the results of, or make presentations related to, the Study, provided that any publications or presentations to be made within 2 years after completion of the Study shall require the Sponsor's prior written consent.
Publication restrictions are in place

Restriction type: OTHER