Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Sodium Zirconium Cyclosilicate (SZC) Reduced Dose Level, Zirconium Cyclosilicate Reduced Dose Level, Sodium Zirconium Cyclosilicate (SZC) Dose Level 1 (DL1), Zirconium Cyclosilicate Dose Level 1
Zirconium Cyclosilicate · 8 trials · 1 indication
Comparison between placebo and each SZC treatment group (high to low) with regard to the mean S-K level during the randomized treatment phase days 8-29. Mixed-effects models were used to estimate least-squares means.
A subject was considered to be a responder if, during the evaluation period, they maintained a pre-dialysis serum potassium (S-K) between 4.0 and 5.0 mmol/L on at least 3 out of 4 dialysis treatments following the long inter-dialytic interval (LIDI) and did not receive rescue therapy. Subjects with no data during the evaluation period were classified as non-responders. The S-K levels used for this analysis were based on the measurements obtained by the central laboratory.
The sensitivity analysis assessed the impact of subjects classified as non-responders due to missing serum potassium (S-K) data. Missing central lab (c-lab) pre-dialysis values were imputed using corresponding pre-dialysis i-STAT (a portable blood analyser) measurements. In addition, a "last observation carried forward" (LOCF) approach was utilized to further impute missing values of pre-dialysis S-K during the evaluation period. This technique will replace missing c-lab S-K values with the last available non-missing pre-dialysis LIDI observation recorded for that patient (and this could be a c-lab value or an imputed c-lab value). The Primary endpoint analysis was repeated on the imputed data.
The number of patients who experienced any AE, including those which were serious (SAE), had an outcome of death, were severe, led to discontinuation of ZS or were causally related to ZS are presented for the MP. AEs of special interest are also presented, including oedema-related AEs, cardiac failure and hypertension.
The least squares means (LS-means) are derived from a linear regression model of absolute change in S-K at 4h with the following covariates: treatment group; baseline S-K; time from the start of dosing insulin to the start of dosing SZC/placebo and the dose (units/kg) of the first course of insulin. The 95% CI is associated with LS-Means.
Blood samples for determination of potassium were collected pre-dose, and at 1, 2, and 4 hours post Dose 1 on Day 1. An additional sample was collected at 90 minutes post Dose 2 on Day 1 if i-STAT potassium values at the 4-hour post Dose 1 time point was ≥ 6.1 or \<4.0 mmol/L. On Day 2 samples were analysed pre-dose, and 1 and 4 hours post Dose 1. S-K levels were analysed at the Central Laboratory. Natural logarithm of S-K from 0 to 48 hours post dose are modelled by the random coefficients model including fixed effects of intercept, time, time x treatment and patient-level random effects for time and intercept. Exponential rate of change refers to the slope estimate from the random coefficients model.
The 48- hour urine potassium excretion on Study Days 3 and 4 (baseline) will be compared with 48-hour urine potassium excretion on Study Days 7 and 8 (on study drug).
| Arm | Type | Description |
|---|---|---|
| Sodium Zirconium Cyclosilicate 10g | EXPERIMENTAL | Suspension administered 10g orally once daily for 28 days after the open label initial phase. |
| Sodium Zirconium Cyclosilicate 5g | EXPERIMENTAL | Suspension administered 5g orally once daily for 28 days after the open label initial phase. |
| Matching Placebo | PLACEBO_COMPARATOR | Suspension administered orally placebo once daily for 28 days after the open label initial phase. |
| Sodium Zirconium Cyclosilicate (SZC) | EXPERIMENTAL | Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) Single dose contains from 1 to 3 sachets of SZC 5g depending on dose level assigned to a patient per non-dialysis days. |
| Placebo | PLACEBO_COMPARATOR | Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) Single dose contains from 1 to 3 sachets of Placebo depending on dose level assigned to a patient per non-dialysis days. |
| Sodium Zirconium Cyclosilicate (ZS) | EXPERIMENTAL | Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) Single dose contains from 1 to 3 sachets of ZS 5g depending on dose level assigned to a patient per non-dialysis days. |
| Sodium Zirconium Cyclosilicate | EXPERIMENTAL | Correction Phase Dosing: Sodium Zirconium Cyclosilicate 10 g three times daily (TID) from 24 to 72 Extended Dosing: Sodium Zirconium Cyclosilicate 5 g once daily (QD). Sodium Zirconium Cyclosilicate dose increased or decreased in increments/decrements of 5 g QD up to a maximum of 15 g QD or a minimum of 5 g every other day (QOD) (or 2.5 g QD) based on i-STAT potassium measurements up to 12 months. |
| Sodium Zirconium Cyclosilicate (ZS) 5g | EXPERIMENTAL | Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase. |
| Sodium Zirconium Cyclosilicate (ZS) 10g | EXPERIMENTAL | Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase. |
| ZS+insulin+glucose | EXPERIMENTAL | ZS will be administered in addition to insulin and glucose. Insulin and glucose is the current standard of care to treat serum potassium ≥5.8mmol/L. |
| Placebo+insulin+glucose | PLACEBO_COMPARATOR | Placebo will be administered in addition to insulin and glucose. Insulin and glucose is the current standard of care to treat serum potassium ≥5.8mmol/L. |
| ZS 5g, qd | EXPERIMENTAL | Subjects randomized to this arm will receive ZS 5 g qd in conjunction with breakfast during the ZS treatment period and will be continued with a standard diet. |
| ZS 10g, qd | EXPERIMENTAL | Subjects randomized to this arm will receive ZS 10 g qd in conjunction with breakfast during the ZS treatment period and will be continued with a standard diet. |
| Name | Type | Description |
|---|---|---|
| Sodium Zirconium Cyclosilicate 5g | DRUG | Suspension administered Sodium Zirconium Cyclosilicate 5g orally once daily for 28 days after the open label initial phase with suspension administered Sodium Zirconium Cyclosilicate 10g orally three times per day for at most 2 days. |
| Sodium Zirconium Cyclosilicate 10g | DRUG | Suspension administered Sodium Zirconium Cyclosilicate 10g orally once daily for 28 days after the open label initial phase with suspension administered Sodium Zirconium Cyclosilicate 10g orally three times per day for at most 2 days. |
| Placebo | DRUG | Suspension administered orally placebo once daily for 28 days after the open label initial phase with suspension administered Sodium Zirconium Cyclosilicate 10g orally three times per day for at most 2 days. |
| Sodium Zirconium Cyclosilicate | DRUG | Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) Single dose contains from 1 to 3 sachets of SZC 5g depending on dose level assigned to a patient per non-dialysis days. |
| Sodium Zirconium Cyclosilicate (ZS) | DRUG | Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) . Single dose contains from 1 to 3 sachets of ZS 5g depending on dose level assigned to a patient per non-dialysis days. |
| Zirconium Cyclosilicate | DRUG | Correction Phase Dosing: Sodium Zirconium Cyclosilicate 10 g three times daily (TID) from 24 to 72 Extended Dosing: Sodium Zirconium Cyclosilicate 5 g once daily (QD). Sodium Zirconium Cyclosilicate dose increased or decreased in increments/decrements of 5 g QD up to a maximum of 15 g QD or a minimum of 5 g every other day (QOD) (or 2.5 g QD) based on i-STAT potassium measurements up to 12 months. |
| Sodium Zirconium Cyclosilicate (ZS) 10g | DRUG | Suspension administered 10g orally three times per day, in the first 48-hour of the study for all patients (48-hour open label initial phase) |
| Sodium Zirconium Cyclosilicate (ZS) 5g | DRUG | Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase. |
| Sodium Zirconium Cyclosilicate(ZS) | DRUG | Suspension administered orally for a treatment period of 24h. Single dose contains 2 sachets of ZS 5g. 10g administered up to three times over 10h (at 0, 4 and 10h). |
| Insulin | DRUG | Insulin 0.1 units/kg administered as a bolus or for up to 30 minutes. |
| Glucose | DRUG | Glucose 25g administered IV \<15 minutes before the insulin. |
Inclusion Criteria: 1. Provision of informed consent (pre-screening consent) prior to any study specific procedures 2. Female and male patients aged ≥18 and ≤ 90 years 3. Provision of informed consent prior to any study specific procedures 4. Two consecutive i-STAT potassium values, measured 60 min...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| AstraZeneca PLC | AZN | 3 | PHASE3 | Zirconium Cyclosilicate Reduced Dose Level, Zirconium Cyclosilicate Dose Level 1, Zirconium Cyclosilicate Dose During 28 Day Maintenance Phase |
Zirconium Cyclosilicate is an investigational small molecule being developed for the treatment of hyperkalemia, a condition of elevated potassium levels in the blood. It is being studied in the therapeutic area of nephrology. The drug is currently in Phase 3 clinical development and has not been approved by regulatory authorities.
Zirconium Cyclosilicate is being developed by AstraZeneca PLC, a biopharmaceutical company listed on the stock exchange under the ticker symbol AZN. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with hyperkalemia.
Zirconium Cyclosilicate is in Phase 3 clinical development for the treatment of hyperkalemia. The drug is investigational and has not yet received regulatory approval. It has completed eight clinical trials with a total enrollment of 1,212 participants, all of which have been completed.
Zirconium Cyclosilicate has been studied in several clinical trials, including NCT03127644, a Phase 2/3 dose-response study in Japan with 103 participants; NCT03283267, a Phase 1 study in healthy Chinese subjects in Hong Kong with 22 participants; NCT03337477, a Phase 2 study in patients with potassium levels ≥5.8 across multiple countries with 70 participants; and NCT04217590, a Phase 3 study in Chinese subjects with 134 participants.
Yes, Zirconium Cyclosilicate is also known as Sodium Zirconium Cyclosilicate (SZC) Reduced Dose Level, Zirconium Cyclosilicate Reduced Dose Level, Sodium Zirconium Cyclosilicate (SZC) Dose Level 1 (DL1), and Zirconium Cyclosilicate Dose Level 1. These alternative names refer to the same investigational drug being developed by AstraZeneca.