Trial Outcomes & Findings for Open-label Safety & Efficacy of ZS (Sodium Zirconium Cyclosilicate)10g qd to Extend Study ZS-004 in Hyperkalemia. (NCT NCT02107092)

Last Updated: 2018-08-15

Results Overview

The proportions of subjects with average serum potassium (S-K) values ≤ 5.1 mmol/L during Extended Dosing Study Days 8 to 337, inclusive

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

123 participants

Primary outcome timeframe

11 months

Results posted on

2018-08-15

Participant Flow

Participants took part in the study at 30 outpatient sites in the United States, Australia and South Africa from 10 May 2014 to 14 July 2015.

Participants that completed Study ZS-004 (NCT02088073) Extended Dosing (ED) Phase Study Day 29 Visit or discontinued Study ZS-004 during the ED Phase due to hypo- or hyperkalemia, had a mean i-STAT potassium value between 3.5 and 6.2 mmol/L, and were able to start dosing in Study ZS-004E within 2 days after the last dose of study drug in ZS-004.

Participant milestones

Participant milestones
Measure	Extended Dosing Phase: ZS (Sodium Zirconium Cyclosilicate) QD ZS 10g QD starting dose. ZS dose was increased or decreased in increments/ decrements of 5g QD to maximum of 15g QD or minimum of 5g every other day (QOD) if i-STAT potassium values increased to \> 5.5 mmol/L or decreased to between 3.0 and 3.4 mmol/L, respectively.
Overall Study STARTED	123
Overall Study COMPLETED	79
Overall Study NOT COMPLETED	44

Reasons for withdrawal

Reasons for withdrawal
Measure	Extended Dosing Phase: ZS (Sodium Zirconium Cyclosilicate) QD ZS 10g QD starting dose. ZS dose was increased or decreased in increments/ decrements of 5g QD to maximum of 15g QD or minimum of 5g every other day (QOD) if i-STAT potassium values increased to \> 5.5 mmol/L or decreased to between 3.0 and 3.4 mmol/L, respectively.
Overall Study Miscellaneous	3
Overall Study Subject compliance	3
Overall Study Hypo-or hyperkalemia	2
Overall Study Met ECG withdrawal criteria	3
Overall Study Physician Decision	3
Overall Study Lost to Follow-up	2
Overall Study Withdrawal by Subject	9
Overall Study Adverse Event	7
Overall Study Expected progression of CKD	12

Baseline Characteristics

Open-label Safety & Efficacy of ZS (Sodium Zirconium Cyclosilicate)10g qd to Extend Study ZS-004 in Hyperkalemia.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Extended Dosing Phase: ZS (Sodium Zirconium Cyclosilicate) QD n=121 Participants ZS 10g QD starting dose. ZS dose was increased or decreased in increments/ decrements of 5g QD to maximum of 15g QD or minimum of 5g every other day (QOD) if i-STAT potassium values increased to \> 5.5 mmol/L or decreased to between 3.0 and 3.4 mmol/L, respectively.
Age, Continuous	63.7 Years STANDARD_DEVIATION 12.29 • n=99 Participants
Sex: Female, Male Female	51 Participants n=99 Participants
Sex: Female, Male Male	70 Participants n=99 Participants
Race/Ethnicity, Customized Asian	2 Participants n=99 Participants
Race/Ethnicity, Customized Black or African American	11 Participants n=99 Participants
Race/Ethnicity, Customized White	107 Participants n=99 Participants
Race/Ethnicity, Customized Other	1 Participants n=99 Participants
Study ZS-004 Acute Phase S-K baseline < 5.5 mmol/L	54 Participants n=99 Participants
Study ZS-004 Acute Phase S-K baseline 5.5-< 6.0 mmol/L	53 Participants n=99 Participants
Study ZS-004 Acute Phase S-K baseline ≥ 6.0 mmol/L	14 Participants n=99 Participants
Acute Phase eGFR at baseline <60 mL/min	90 Participants n=99 Participants
Acute Phase eGFR at baseline ≥ 60 mL/min	31 Participants n=99 Participants
Cormordid conditions and concomitant medications which may contirubute to hyperkalemia RAAS inhibitor medication	83 Participants n=99 Participants
Cormordid conditions and concomitant medications which may contirubute to hyperkalemia Diabetes mellitus	80 Participants n=99 Participants
Cormordid conditions and concomitant medications which may contirubute to hyperkalemia Chronic kidney disease	76 Participants n=99 Participants
Cormordid conditions and concomitant medications which may contirubute to hyperkalemia Heart failure	50 Participants n=99 Participants

PRIMARY outcome

Timeframe: 11 months

Population: Entered Extended Dosing Phase, received study drug and had post baseline S-K values during the Extended Dosing Phase. The analysis population includes 121 subjects, where there is one subject who only had end-of-study post-baseline measurement and therefore was not presented in the participants analyzed.

The proportions of subjects with average serum potassium (S-K) values ≤ 5.1 mmol/L during Extended Dosing Study Days 8 to 337, inclusive

Outcome measures

Outcome measures
Measure	Extended Dosing Phase: ZS (Sodium Zirconium Cyclosilicate) QD n=120 Participants ZS 10g QD starting dose. ZS dose was increased or decreased in increments/ decrements of 5g QD to maximum of 15g QD or minimum of 5g every other day (QOD) if i-STAT potassium values increased to \> 5.5 mmol/L or decreased to between 3.0 and 3.4 mmol/L, respectively.
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L ED Study Day 8	0.875 Proportion of Participants Interval 0.802 to 0.928
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L ED Study Day 15	0.822 Proportion of Participants Interval 0.741 to 0.886
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L ED Study Day 22	0.797 Proportion of Participants Interval 0.713 to 0.865
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L ED Study Day 29	0.862 Proportion of Participants Interval 0.786 to 0.919
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L ED Study Day 36	0.848 Proportion of Participants Interval 0.768 to 0.909
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L ED Study Day 43	0.793 Proportion of Participants Interval 0.705 to 0.864
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L ED Study Day 50	0.796 Proportion of Participants Interval 0.708 to 0.868
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L ED Study Day 57	0.766 Proportion of Participants Interval 0.675 to 0.843
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L ED Study Day 85	0.807 Proportion of Participants Interval 0.709 to 0.833
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L ED Study Day 113	0.798 Proportion of Participants Interval 0.696 to 0.877
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L ED Study Day 141	0.815 Proportion of Participants Interval 0.713 to 0.892
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L ED Study Day 169	0.771 Proportion of Participants Interval 0.656 to 0.863
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L ED Study Day 197	0.809 Proportion of Participants Interval 0.695 to 0.894
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L ED Day Study 225	0.846 Proportion of Participants Interval 0.735 to 0.924
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L ED Study Day 253	0.778 Proportion of Participants Interval 0.655 to 0.873
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L ED Study Day 281	0.833 Proportion of Participants Interval 0.715 to 0.917
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L ED Study Day 309	0.828 Proportion of Participants Interval 0.706 to 0.914
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L ED Study Day 337	0.843 Proportion of Participants Interval 0.714 to 0.93
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L ED Study Day 337/Exit	0.783 Proportion of Participants Interval 0.699 to 0.853
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L ED Study Days 8-337 Average	0.883 Proportion of Participants Interval 0.812 to 0.935

SECONDARY outcome

Timeframe: 11 months

The proportions of subjects with average S-K values ≤ 5.5 mmol/L during Extended Dosing Study Days 8 to 337, inclusive

Outcome measures

Outcome measures
Measure	Extended Dosing Phase: ZS (Sodium Zirconium Cyclosilicate) QD n=120 Participants ZS 10g QD starting dose. ZS dose was increased or decreased in increments/ decrements of 5g QD to maximum of 15g QD or minimum of 5g every other day (QOD) if i-STAT potassium values increased to \> 5.5 mmol/L or decreased to between 3.0 and 3.4 mmol/L, respectively.
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L ED Study Day 337/Exit	0.942 Proportion of Participants Interval 0.884 to 0.976
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L ED Study Day 8	0.950 Proportion of Participants Interval 0.894 to 0.981
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L ED Study Day 15	0.932 Proportion of Participants Interval 0.871 to 0.97
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L ED Study Day 22	0.975 Proportion of Participants Interval 0.927 to 0.995
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L ED Study Day 29	0.957 Proportion of Participants Interval 0.902 to 0.986
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L ED Study Day 36	0.955 Proportion of Participants Interval 0.899 to 0.985
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L ED Study Day 43	0.946 Proportion of Participants Interval 0.886 to 0.98
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L ED Study Day 50	0.935 Proportion of Participants Interval 0.871 to 0.974
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L ED Study Day 57	0.944 Proportion of Participants Interval 0.882 to 0.979
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L ED Study Day 85	0.943 Proportion of Participants Interval 0.872 to 0.981
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L ED Study Day 113	0.940 Proportion of Participants Interval 0.867 to 0.98
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L ED Study Day 141	0.938 Proportion of Participants Interval 0.862 to 0.98
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L ED Study Day 169	0.929 Proportion of Participants Interval 0.841 to 0.976
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L ED Study Day 197	0.941 Proportion of Participants Interval 0.856 to 0.984
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L ED Day Study 225	0.985 Proportion of Participants Interval 0.917 to 1.0
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L ED Study Day 253	0.937 Proportion of Participants Interval 0.845 to 0.982
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L ED Study Day 281	0.950 Proportion of Participants Interval 0.861 to 0.99
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L ED Study Day 309	0.914 Proportion of Participants Interval 0.81 to 0.971
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L ED Study Day 337	0.980 Proportion of Participants Interval 0.896 to 1.0
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L ED Study Days 8-337 Average	1.000 Proportion of Participants Interval 0.97 to 1.0

Adverse Events

ZS (Sodium Zirconium Cyclosilicate) QD Extended Phase Dosing

Serious events: 24 serious events

Other events: 82 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ZS (Sodium Zirconium Cyclosilicate) QD Extended Phase Dosing n=123 participants at risk ZS 10g QD starting dose increased or decreased in increments/ decrements of 5g QD to maximum of 15g QD or minimum of 5g QOD if i-STAT potassium values increased to \> 5.5 mmol/L or decreased to between 3.0 and 3.4 mmol/L, respectively.
Blood and lymphatic system disorders Anaemia	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Cardiac disorders Acute myocardial infarction	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Cardiac disorders Cardiac failure	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Cardiac disorders Cardiac failure congestive	1.6% 2/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Cardiac disorders Myocardial infarction	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Eye disorders Retinal artery occlusion	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Gastrointestinal disorders Abdominal Pain	1.6% 2/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Gastrointestinal disorders Gastritis haemorrhagic	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
General disorders Chest pain	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Infections and infestations Diabetic foot infection	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Infections and infestations Gangrene	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Infections and infestations Lobar pneumonia	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Infections and infestations Localised infection	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Infections and infestations Morganella infection	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Infections and infestations Pneumonia	1.6% 2/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Infections and infestations Sepsis	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Infections and infestations Tooth abscess	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Infections and infestations Urinary tract infection	1.6% 2/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Injury, poisoning and procedural complications Patella fracture	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Metabolism and nutrition disorders Hyperkalaemia	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Nervous system disorders Cerebrovascular accident	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Nervous system disorders Convulsion	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.6% 2/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Skin and subcutaneous tissue disorders Dry gangrene	0.81% 1/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.

Other adverse events

Other adverse events
Measure	ZS (Sodium Zirconium Cyclosilicate) QD Extended Phase Dosing n=123 participants at risk ZS 10g QD starting dose increased or decreased in increments/ decrements of 5g QD to maximum of 15g QD or minimum of 5g QOD if i-STAT potassium values increased to \> 5.5 mmol/L or decreased to between 3.0 and 3.4 mmol/L, respectively.
Blood and lymphatic system disorders Anaemia	4.9% 6/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Cardiac disorders Cardiac failure	2.4% 3/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Gastrointestinal disorders Abdominal pain	2.4% 3/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Gastrointestinal disorders Constipation	5.7% 7/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Gastrointestinal disorders Diarrhoea	3.3% 4/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Gastrointestinal disorders Nausea	3.3% 4/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Gastrointestinal disorders Vomiting	3.3% 4/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
General disorders Oedema	3.3% 4/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
General disorders Oedema peripheral	8.1% 10/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Immune system disorders Seasonal allergy	2.4% 3/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Infections and infestations Gastroenteritis	2.4% 3/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Infections and infestations Influenza	2.4% 3/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Infections and infestations Pneumonia	2.4% 3/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Infections and infestations Upper respiratory tract infection	4.1% 5/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Infections and infestations Urinary tract infection	8.9% 11/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Investigations Blood urea increased	2.4% 3/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Metabolism and nutrition disorders Gout	3.3% 4/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Metabolism and nutrition disorders Hyperlipidemia	3.3% 4/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Metabolism and nutrition disorders Hypomagnesaemia	2.4% 3/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Musculoskeletal and connective tissue disorders Arthralgia	2.4% 3/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Musculoskeletal and connective tissue disorders Back pain	2.4% 3/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Musculoskeletal and connective tissue disorders Muscle spasms	4.9% 6/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Nervous system disorders Dizzines	2.4% 3/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Nervous system disorders Headache	3.3% 4/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	2.4% 3/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Respiratory, thoracic and mediastinal disorders Cough	2.4% 3/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
Vascular disorders Hypertension	12.2% 15/123 • Eleven months The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.

Additional Information

AstraZeneca Clinical Study Information Center

ZS Pharma, Inc.

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee ZS Pharma has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome. The PIs also agree for data to be presented first as a joint, multi-center publication.
Publication restrictions are in place

Restriction type: OTHER