Table 2.

Primary and secondary endpoints during the maintenance phase (full analysis set) ordered according to the sequential closed testing procedure

	SZC 10 g (N = 99)	SZC 5 g (N = 99)	Placebo (N = 50)
Sequential closed testing procedure endpoints
Mean central‐laboratory K+ during days 8–29 (primary endpoint)a	n = 96	n = 95	n = 49
Geometric LSM (95% CI) (mmol/L)	4.38 (4.27, 4.50)	4.81 (4.69, 4.94)	5.32 (5.16, 5.49)
Geometric mean ratio (95% CI) vs. placebo	0.82 (0.80, 0.85)	0.90 (0.88, 0.93)
2nd and 3rd controlled P‐values, respectively	<0.001	<0.001
Patients remaining normokalaemic on day 29b	n = 97	n = 99	n = 50
n (%)	75 (77.3)	58 (58.6)	12 (24.0)
Adjusted odds ratio (95% CI) vs. placebo	18.19 (7.16, 46.21)	6.34 (2.69, 14.98)
4th and 5th controlled P‐values, respectively	<0.001	<0.001
Days normokalaemic during MP days 8–29c	n = 97	n = 99	n = 50
LSM (95% CI)	15.62 (13.37, 17.88)	10.81 (8.62, 13.00)	3.54 (0.88, 6.21)
LSM difference (95% CI) vs. placebo	12.08 (9.12, 15.04)	7.27 (4.32, 10.21)
6th and 7th controlled P‐values, respectively	<0.001	<0.001
Patients with hyperkalaemia (>5.1 mmol/L)d	n = 97	n = 99	n = 50
n (%) with hyperkalaemia	45 (46.4)	66 (66.7)	47 (94.0)
Adjusted hazard ratio (95% CI) vs. placebo	0.16 (0.10, 0.25)	0.44 (0.30, 0.66)
8th and 9th controlled P‐values, respectively	<0.001	<0.001
Other endpoints
Serum aldosterone (pmol/L)e	n = 68	n = 76	n = 40
Mean change from BL at day 29 (95% CI)	−90 (−112, −68)	−103 (−151, −54)	41 (−22, 104)
Mean difference (95% CI) vs. placebo	−131 (−187, −76)	−144 (−224, −63)
Nominal P‐value	<0.001	0.001
Plasma renin, pmol/Le	n = 78	n = 75	n = 37
Mean change from BL at day 29 (95% CI)	−1.56 (−2.50, −0.62)	−0.27 (−0.51, −0.04)	−0.25 (−1.16, 0.66)
Mean difference (95% CI) vs. placebo	−1.31 (−2.80, 0.18)	−0.02 (−0.73, 0.68)
Nominal P‐value	0.085	0.949

BL, baseline; CI, confidence interval; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HF, heart failure; LSM, least squares mean; N, number in the full analysis set; n, number evaluable at analysis time point; RAASi, renin–angiotensin–aldosterone system inhibitor; SZC, sodium zirconium cyclosilicate.

^aBack‐transformed (e ^value) geometric LSM and geometric mean ratio were derived from a mixed‐effects model of log‐transformed central‐laboratory K⁺ levels. Fixed effects were treatment group, visit, treatment‐by‐visit interaction, and baseline covariates (central‐laboratory K⁺ for correction and maintenance phases, eGFR, age category, country, RAASi use, and presence of CKD, HF, and diabetes mellitus). Patient was a random effect.

^bNormokalaemia was defined as central‐laboratory K⁺ 3.5–5.0 mmol/L, inclusive. Day 29 was day 29 or day of last dose of study treatment if earlier. Adjusted odds ratios were calculated as the exponential of coefficients derived from a logistic regression model with terms for treatment (not including visit and treatment‐by‐visit interaction) and baseline covariates as listed in footnote a.

^cThe number of normokalaemic days was calculated assuming that the time interval between assessments was normokalaemic only if both the beginning and end assessment for that time interval showed normal central‐laboratory K⁺ values. If an intermediate assessment time point was missing, the time interval was extended until the next non‐missing time point. LSM and LSM differences were derived from a linear regression model with terms for treatment (not including visit and treatment‐by‐visit interaction) and baseline covariates as listed in footnote a.

^dMedian time to hyperkalaemia values were derived from Kaplan–Meier analysis. Adjusted hazard ratios were derived from a Cox proportional hazards regression model with terms for treatment (not including visit and treatment‐by‐visit interaction) and baseline covariates as listed in footnote a.

^e P‐values for mean differences were derived from a two‐sample, two‐sided t‐test. Tests of serum aldosterone and plasma renin were not under type I error control, and P‐values are thus referred to as nominal.