Hyperkalemia
Conditions
Keywords
Treatment of Hyperkalemia, Hyperkalemia, Potassium, Chronic Kidney Disease
Brief summary
The purpose of this study is to evaluate the change in serum potassium levels from start of treatment to Day 14, when patiromer is administered at different doses, once daily, in children 2 - \< 18 years of age with chronic kidney disease (CKD) and hyperkalemia (too much potassium in the blood). Another purpose of the study is to evaluate the safety and tolerability of patiromer in children 2 - \< 18 years of age with CKD and hyperkalemia.
Detailed description
Up to 54 subjects, 2 - \< 18 years of age with CKD (estimated glomerular filtration rate \[eGFR\] \< 90 mL/min/1.73 m2 ) and hyperkalemia (two potassium measurements of 5.1 to \< 6.5 mEq/L performed on separate days) will be enrolled in this open-label, multiple-dose, Phase 2 study. The study will include two treatment phases: Pharmacodynamic (PD; drug effect on potassium) / Dose Finding Phase consisting of the initial 14-day dose finding period followed by an up to 5.5-month Long-Term Treatment Phase for a total study participation duration for individual subjects of up to 6.5 months (includes a 2 week follow up period).
Interventions
DRUGPatiromer
4.2 g/day, 8.4 g/day and 16.8 g/day
Sponsors
Vifor Pharma, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Written assent (when applicable) and written informed consent by a legally authorized representative provided prior to participation in the study * Age 2 - \<18 years old * CKD defined by the estimated glomerular filtration rate (eGFR) \<90 mL/min/1.73m2, including renal transplant subjects, based on local creatinine measurement at screening * Two potassium measurements of 5.1 to \< 6.5 mEq/L performed on separate days * In the opinion of the study doctor, is expected to require treatment for hyperkalemia for at least 6 month * If taking any renin-angiotensin-aldosterone system inhibitors (RAASi) beta blockers or diuretic medications, must be on a stable dose for at least 28 days prior to Screening * Negative pregnancy test in females of child-bearing potential
Exclusion criteria
* Pseudohyperkalemia due to hemolysis or to abnormally high numbers of platelets (\>500,000/mm3), leukocytes (\>70,000/mm3), or erythrocytes (hematocrit \>55%) at Screening based on results obtained locally * Evidence of potassium-related electrocardiogram (ECG) changes at Screening * Any of the following kidney conditions: maintenance hemodialysis or peritoneal dialysis, renal artery stenosis, and acute kidney injury or a history of acute renal insufficiency in the past 3 months * Severe disorder of stomach or intestines including surgery that could affect gastrointestinal transit of the drug * Increased liver enzymes (ALT, AST \> 3 times upper limit of normal) at Screening * Active cancer, currently on cancer treatment or history of cancer in the past 2 years (except for non-melanoma skin cancer) * Heart or liver transplant, or anticipated need for transplant during the study treatment period including a scheduled kidney transplant recipient. (Note: patients currently on a kidney transplant wait list are not excluded unless there is an identified donor). * Alcohol abuse or substance use disorder within 1 year of Screening * Subjects currently being treated with or having taken any one of the following medications (includes resins) in the 7 days prior to Screening: sodium or calcium polystyrene sulfonate, drospirenone * Use of certain medications that can affect blood potassium levels if doses have not been stable for at least 14 days prior to Screening or if doses are anticipated to change during the 14-day PD / Dose Finding Phase * Use of investigational product within 30 days of screening or within 5 half-lives, whichever is longer * Known hypersensitivity to patiromer or its components * In the opinion of the Investigator, any medical condition, uncontrolled systemic disease, or serious intercurrent illness that would significantly decrease study compliance or jeopardize the safety of the subject or potentially affect the quality of the data
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Serum Potassium Levels | from Baseline to Day 14 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects With Serum Potassium Levels in the Range of 3.8 - 5.0 mEq/L | Day 14 and Week 26 | Day 14: Initial PD / Dose Finding Phase. Week 26: Long-Term Treatment Phase. |
Countries
Bulgaria, Canada, Georgia, Germany, Poland, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Patiromer administrated to pediatric participants (12 to \<18 years of age), with chronic kidney disease (CKD) and hyperkalemia.
The starting dose levels of Patiromer for Cohort 1 were: 4.2 g/day, 8.4 g/day and 16.8 g/day, starting with the lowest dose level, depending on the participant's median weights.
Once-daily administration up to 26 weeks including screening at Day 1 followed by 14-days (Pharmacodynamic dose-finding phase), 22 weeks (Long-term treatment phase), and a 2-week follow-up period consisting of 1 follow-up visit and 1 follow-up phone call. | 14 |
| Cohort 2 Patiromer administrated to pediatric participants (6 to \<12 years of age), with chronic kidney disease (CKD) and hyperkalemia.
The starting dose levels of Patiromer for Cohoer1 1 were: 2 g/day, 4 g/day and 8 g/day, starting with the lowest dose level, depending on the participant's median weights.
Once-daily administration up to 26 weeks including screening at Day 1 followed by 14-days (Pharmacodynamic dose-finding phase), 22 weeks (Long-term treatment phase), and a 2-week follow-up period consisting of 1 follow-up visit and 1 follow-up phone call. | 9 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 14 Participants | 9 Participants | 23 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 14.5 years STANDARD_DEVIATION 1.99 | 8.0 years STANDARD_DEVIATION 2 | 12.0 years STANDARD_DEVIATION 3.78 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 9 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Georgia | 3 participants | 1 participants | 4 participants |
| Region of Enrollment Germany | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Poland | 1 participants | 1 participants | 2 participants |
| Region of Enrollment Ukraine | 6 participants | 7 participants | 13 participants |
| Region of Enrollment United States | 2 participants | 0 participants | 2 participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 9 Participants |
| Sex: Female, Male Male | 11 Participants | 3 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 9 |
| other Total, other adverse events | 10 / 14 | 5 / 9 |
| serious Total, serious adverse events | 0 / 14 | 0 / 9 |
Outcome results
Primary
Change in Serum Potassium Levels
Time frame: from Baseline to Day 14
Population: The efficacy population includes all subjects who have taken at least 1 dose of patiromer.~As the safety population and efficacy population are the same in this study, all analyses are displayed with 1 population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Change in Serum Potassium Levels | -0.50 mEq/l | Standard Deviation 0.542 |
| Cohort 2 | Change in Serum Potassium Levels | -0.14 mEq/l | Standard Deviation 0.553 |
Secondary
Proportion of Subjects With Serum Potassium Levels in the Range of 3.8 - 5.0 mEq/L
Day 14: Initial PD / Dose Finding Phase. Week 26: Long-Term Treatment Phase.
Time frame: Day 14 and Week 26
Population: The efficacy population includes all subjects who have taken at least 1 dose of patiromer.~As the safety population and efficacy population are the same in this study, all analyses are displayed with 1 population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Proportion of Subjects With Serum Potassium Levels in the Range of 3.8 - 5.0 mEq/L | Day 14 | 50.0 percentage of participants (%) |
| Cohort 1 | Proportion of Subjects With Serum Potassium Levels in the Range of 3.8 - 5.0 mEq/L | Week 26 | 81.8 percentage of participants (%) |
| Cohort 2 | Proportion of Subjects With Serum Potassium Levels in the Range of 3.8 - 5.0 mEq/L | Day 14 | 12.5 percentage of participants (%) |
| Cohort 2 | Proportion of Subjects With Serum Potassium Levels in the Range of 3.8 - 5.0 mEq/L | Week 26 | 22.2 percentage of participants (%) |