Hyperphosphatemia
Conditions
Keywords
S-phosphate, hyperphosphatemia, hemodialysis, ESRD
Brief summary
Randomized. double blind, placebo controlled, parallel arms dose finding study with a 4 weeks treatment period
Detailed description
The study consists of a screening period of approximately 1 week, a wash out period of up to 3 weeks, where existing phosphate lowering medication is withheld, a 4-week treatment period and a follow-up period of up to 2 weeks, during which patients are put back on their pre washout phosphate lowering medication. The wash out period will be either 1 week, 2 weeks or 3 weeks depending on the increase in s-phosphate levels. There are 7 parallel treatment arms in the study with bid and od treatment regimens. Laboratory efficacy endpoints and safety assessments will be evaluated at various times throughout the study. The target population of the study is: male or female patients, above18 years of age with End Stage Renal Disease (ESRD) on chronic maintenance hemodialysis (HD) 3 times a week for a minimum of 3 months.
Interventions
DRUGAZD1722
AZD1722, oral tablet
DRUGPlacebo
Placebo bid, double dummy technique
Sponsors
Ardelyx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Females and males aged ≥18 years 2. Chronic maintenance hemodialysis 3 x/week for a at least 3 months 3. Prescribed and taking at least 3 doses of phosphate binder per day 4. Serum phosphate levels should be between 3.5 and 8.0 mg/dL ; 1.13 mmol/L and 2.58 mmol/L (inclusive) at screening 5. Total serum calcium levels 2.0 - 2.6 mmol/L inclusive at screening 6. For randomization in the study, after up to 3 weeks wash out of phosphate binders, patients must have serum phosphate levels of at least 6. 0 mg/dL (1.94 mmol/L) but below 10 mg/dL (3.23 mmol/L) and have had an increase of at least 1.5 mg/dL (0.48 mmol/L) vs pre wash out
Exclusion criteria
1. Severe hyperphosphatemia defined as \>10 mg/dL on Phosphate-binders at all time points during clinical routine monitoring for the 3 preceding months before screening visit. 2. Serum parathyroid hormone \>1200 pg/mL 3. Significant metabolic acidosis 4. Clinical signs of hypovolemia at randomization \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Phosphate Levels | End of wash out (pre randomization value) to end of treatment (Day 29) | Change in serum phosphate levels from the end of wash out (pre randomization value) to end of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Calcium x Phosphorus Product | End of wash out (pre randomization value) to end of treatment (Day 29) | Change from baseline (end of wash out) in calcium x phosphorus product |
Countries
Poland, Slovakia, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1 mg Bid 1 mg AZD1722 bid
AZD1722: tenapanor, oral tablet | 23 |
| 3 mg Bid 3 mg AZD1722 bid
AZD1722: tenapanor, oral tablet | 21 |
| 10 mg Bid 10 mg AZD1722 bid
AZD1722: tenapanor, oral tablet | 23 |
| 30 mg Bid 30 mg AZD1722 bid
AZD1722: tenapanor, oral tablet | 26 |
| 3 mg od 3 mg AZD1722 od
AZD1722: tenapanor, oral tablet | 22 |
| 30 mg od 30 mg AZD1722 od
AZD1722: tenapanor, oral tablet | 21 |
| Placebo Placebo (double dummy technique)
Placebo: Placebo bid, double dummy technique | 26 |
| Total | 162 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 4 | 3 | 10 | 2 | 8 | 2 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 2 | 1 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 3 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 1 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | 1 mg Bid | Total | Placebo | 30 mg od | 3 mg od | 30 mg Bid | 10 mg Bid | 3 mg Bid |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 57.9 years STANDARD_DEVIATION 14.79 | 59.1 years STANDARD_DEVIATION 14.1 | 56.1 years STANDARD_DEVIATION 13.14 | 58.2 years STANDARD_DEVIATION 15.75 | 57.6 years STANDARD_DEVIATION 15.78 | 59.7 years STANDARD_DEVIATION 12.96 | 62.7 years STANDARD_DEVIATION 12.53 | 61.5 years STANDARD_DEVIATION 11.21 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 48 Participants | 6 Participants | 6 Participants | 8 Participants | 4 Participants | 10 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 114 Participants | 20 Participants | 15 Participants | 14 Participants | 22 Participants | 13 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 8 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 9 Participants | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 35 Participants | 4 Participants | 3 Participants | 6 Participants | 9 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 106 Participants | 17 Participants | 16 Participants | 13 Participants | 15 Participants | 16 Participants | 12 Participants |
| serum phosphorus | 7.55 mg/dL STANDARD_DEVIATION 1.003 | 7.68 mg/dL STANDARD_DEVIATION 1.124 | 7.87 mg/dL STANDARD_DEVIATION 1.488 | 7.61 mg/dL STANDARD_DEVIATION 0.847 | 7.73 mg/dL STANDARD_DEVIATION 1.276 | 7.76 mg/dL STANDARD_DEVIATION 1.183 | 7.32 mg/dL STANDARD_DEVIATION 1.063 | 7.92 mg/dL STANDARD_DEVIATION 1.005 |
| Sex: Female, Male Female | 16 Participants | 104 Participants | 16 Participants | 13 Participants | 12 Participants | 17 Participants | 15 Participants | 15 Participants |
| Sex: Female, Male Male | 7 Participants | 58 Participants | 10 Participants | 8 Participants | 10 Participants | 9 Participants | 8 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 23 | 0 / 21 | 0 / 23 | 0 / 26 | 0 / 22 | 0 / 21 | 0 / 26 |
| other Total, other adverse events | 6 / 23 | 6 / 21 | 11 / 23 | 17 / 26 | 4 / 22 | 11 / 21 | 3 / 26 |
| serious Total, serious adverse events | 2 / 23 | 2 / 21 | 3 / 23 | 2 / 26 | 1 / 22 | 0 / 21 | 4 / 26 |
Outcome results
Primary
Change in Serum Phosphate Levels
Change in serum phosphate levels from the end of wash out (pre randomization value) to end of treatment
Time frame: End of wash out (pre randomization value) to end of treatment (Day 29)
Population: two patients in the 30 mg bid group are not included in the analysis since they had no post randomization serum phosphorus measurements
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1 mg Bid | Change in Serum Phosphate Levels | -.47 mg/dL | Standard Deviation 1.553 |
| 3 mg Bid | Change in Serum Phosphate Levels | -1.18 mg/dL | Standard Deviation 1.391 |
| 10 mg Bid | Change in Serum Phosphate Levels | -1.7 mg/dL | Standard Deviation 2.018 |
| 30 mg Bid | Change in Serum Phosphate Levels | -1.98 mg/dL | Standard Deviation 2.007 |
| 3 mg od | Change in Serum Phosphate Levels | -.56 mg/dL | Standard Deviation 1.763 |
| 30 mg od | Change in Serum Phosphate Levels | -1.11 mg/dL | Standard Deviation 1.469 |
| Placebo | Change in Serum Phosphate Levels | -.54 mg/dL | Standard Deviation 1.802 |
p-value: 0.012ANCOVA
Secondary
Change From Baseline in Calcium x Phosphorus Product
Change from baseline (end of wash out) in calcium x phosphorus product
Time frame: End of wash out (pre randomization value) to end of treatment (Day 29)
Population: The number of patients analyzed are less than the randomized number since the data to accomplish the analysis was not available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1 mg Bid | Change From Baseline in Calcium x Phosphorus Product | -5.16 mg/dL * mg/dL | Standard Deviation 9.75 |
| 3 mg Bid | Change From Baseline in Calcium x Phosphorus Product | -12.02 mg/dL * mg/dL | Standard Deviation 14.02 |
| 10 mg Bid | Change From Baseline in Calcium x Phosphorus Product | -12.44 mg/dL * mg/dL | Standard Deviation 15.94 |
| 30 mg Bid | Change From Baseline in Calcium x Phosphorus Product | -16.6 mg/dL * mg/dL | Standard Deviation 18.01 |
| 3 mg od | Change From Baseline in Calcium x Phosphorus Product | -3.59 mg/dL * mg/dL | Standard Deviation 18.59 |
| 30 mg od | Change From Baseline in Calcium x Phosphorus Product | -11.02 mg/dL * mg/dL | Standard Deviation 11.57 |
| Placebo | Change From Baseline in Calcium x Phosphorus Product | -2.50 mg/dL * mg/dL | Standard Deviation 13.67 |