Dose Finding Study to Treat High Phosphate Levels in the Blood.

• ClinicalTrials.gov Identifier: NCT02081534
• Recruitment Status: Completed
• First Posted: March 7, 2014
• Results First Posted: September 14, 2020
• Last Update Posted: September 14, 2020
• Sponsor: Ardelyx
• Information provided by (Responsible Party): Ardelyx

Tracking Information

• First Submitted Date: March 6, 2014
• First Posted Date: March 7, 2014
• Results First Submitted Date: August 6, 2020
• Results First Posted Date: September 14, 2020
• Last Update Posted Date: September 14, 2020
• Study Start Date: March 2014
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 6, 2014)

Change in Serum Phosphate Levels [ Time Frame: 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 25, 2020)

Change From Baseline in Calcium x Phosphorus Product [ Time Frame: 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

Original Secondary Outcome Measures (submitted: March 6, 2014)

• The number of patients reaching S-phosphate goal [ Time Frame: End of wash out (pre randomization value) to end of treatment (Day 29) ]
  Comparison of the effect of AZD1722 versus placebo on the number of patients reaching serum phosphate goal levels defined as < 5.5 mg/dl (1.78 mmol/L) during 4 weeks of treatment
• Change From Baseline in Calcium x Phosphorus Product [ Time Frame: 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
• Change from pre wash out in S-phosphate levels [ Time Frame: Pre wash out to end of treatment (Day 29) ]
  Comparison of the effect of AZD1722 versus pre wash out phosphate-lowering treatment, by comparing serum phosphate levels during AZD1722 treatment to pre wash out levels
• Safety and tolerability of AZD1722 [ Time Frame: End of wash out (pre randomization value) to end of treatment (Day 29) ]
  To evaluate the safety and tolerability of AZD1722 as assessed by adverse event recording, vital signs, 12-lead electrocardiogram, physical examination, and safety laboratory monitoring
• Dose response relationship [ Time Frame: End of wash out (pre randomization value) to end of treatment (Day 29) ]
  To characterize the dose response relationship of AZD1722 on serum phosphate levels

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Dose Finding Study to Treat High Phosphate Levels in the Blood.
• Official Title: A Phase 2b, Randomized, Double Blind, Placebo-controlled, Parallel Group, Multicentre Dose Finding Study to Evaluate the Efficacy, Safety and Tolerability of AZD1722 to Treat Hyperphosphatemia in End-Stage Renal Disease Patients on Hemodialysis (ESRD-HD)
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Hyperphosphatemia

Intervention

• Drug: AZD1722
  AZD1722, oral tablet
• Drug: Placebo
  Placebo bid, double dummy technique

Study Arms

• Experimental: 1 mg bid
  1 mg AZD1722 bid
  Intervention: Drug: AZD1722
• Experimental: 3 mg bid
  3 mg AZD1722 bid
  Intervention: Drug: AZD1722
• Experimental: 10 mg bid
  10 mg AZD1722 bid
  Intervention: Drug: AZD1722
• Experimental: 30 mg bid
  30 mg AZD1722 bid
  Intervention: Drug: AZD1722
• Experimental: 3 mg od
  3 mg AZD1722 od
  Intervention: Drug: AZD1722
• Experimental: 30 mg od
  30 mg AZD1722 od
  Intervention: Drug: AZD1722
• Placebo Comparator: Placebo
  Placebo (double dummy technique)
  Intervention: Drug: Placebo

• Publications *: Block GA, Rosenbaum DP, Yan A, Greasley PJ, Chertow GM, Wolf M. The effects of tenapanor on serum fibroblast growth factor 23 in patients receiving hemodialysis with hyperphosphatemia. Nephrol Dial Transplant. 2019 Feb 1;34(2):339-346. doi: 10.1093/ndt/gfy061.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 25, 2020): 162
• Original Estimated Enrollment (submitted: March 6, 2014): 300
• Actual Study Completion Date: November 2014
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

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Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Poland, Slovakia, United Kingdom, United States

Administrative Information

• NCT Number: NCT02081534
• Other Study ID Numbers: D5613C00001
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Ardelyx
• Study Sponsor: Ardelyx
• Collaborators: Not Provided

Investigators

• Principal Investigator: Geoffrey A Block, MD; Denver Nephrology PC, Denver, CO 80230

• PRS Account: Ardelyx
• Verification Date: August 2020