A Study to Evaluate Safety, Tolerability and Efficacy of AP306 at Fixed Doses in Dialysis Participants With Hyperphosphatemia

Official title

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety, Tolerability, and Serum Phosphate Lowering Effect of Fixed Dose AP306 in Participants With Hyperphosphatemia Receiving Maintenance Hemodialysis

Overview

This study is being conducted to characterize the safety, tolerability, and efficacy of AP306 at fixed doses in adults with hyperphosphatemia receiving maintenance hemodialysis.

Detailed description

Hyperphosphatemia, one of the most common complications of advanced chronic kidney disease, becomes increasingly prevalent as kidney function declines and is found almost universally in patients with end-stage kidney disease requiring dialysis. Hyperphosphatemia is an independent risk factor for cardiovascular outcomes, fractures, and mortality in patients with chronic kidney disease, especially in patients receiving dialysis.

AP306 is a pan-phosphate transporter inhibitor that may stop phosphate absorption in the gut, controlling hyperphosphatemia.

This is a randomized, double-blind, placebo-controlled, study to characterize the safety, tolerability, and efficacy of AP306 given daily for 8 weeks at fixed doses in adults with hyperphosphatemia receiving maintenance hemodialysis.

Interventions

• Drug AP306 75 mg BID
  AP306 75 mg by mouth, twice daily (150 mg/day). Placebo given once daily. Treatment given daily for 8 weeks.
• Drug AP306 125 mg BID
  AP306 125 mg by mouth, twice daily (250 mg/day). Placebo given once daily. Treatment given daily for 8 weeks.
• Drug AP306 150 mg BID
  AP306 150 mg by mouth, twice daily (300 mg/day). Placebo given once daily. Treatment given daily for 8 weeks.
• Drug AP306 75 mg TID
  AP306 75 mg by mouth, three times daily (225 mg/day). Treatment given daily for 8 weeks.
• Drug AP306 100 mg TID
  AP306 100 mg by mouth, three times daily (300 mg/day). Treatment given daily for 8 weeks.
• Drug AP306 125 mg TID
  AP306 125 mg by mouth, three times daily (375 mg/day). Treatment given daily for 8 weeks.
• Drug Placebo
  Placebo given by mouth, three times daily. Treatment given daily for 8 weeks.

Primary outcome measures

• To investigate the ability of AP306 at different fixed doses to lower serum phosphate in participants with hyperphosphatemia receiving maintenance hemodialysis [Time frame: 8 weeks]

Secondary outcome measures (3)

• To assess the proportion of participants with serum phosphate in the target range [Time frame: 8 weeks]
• To assess the change in serum phosphate from baseline to the end of the Treatment Period [Time frame: 8 weeks]
• To assess the time to response on serum phosphate reduction [Time frame: 8 weeks]

Eligibility criteria

Important Inclusion Criteria:

• Signs a written informed consent form (ICF) and is willing to comply with all study requirements in the study
• Receiving a stable hemodialysis (including hemodialysis, hemodiafiltration, and hemoadsorption) regimen, which is defined as a frequency of three times per week for at least 12 weeks before signing the ICF, and does not plan to change in the study
• Who has a blood phosphate level within the study-required range
• Who has a dialysis adequacy, assessed by single pooled Kt/V (SpKt/V, estimated with blood urea) ≥1.20, at screening or any documented value ≥1.20 within 12 weeks prior to signing the ICF
• If the participant is receiving etelcalcetide, their doses must be unchanged for at least 4 weeks prior to signing the ICF
• If the participant is receiving any of the following therapies, their doses are stable for at least 14 days prior to signing the ICF: phosphate-lowering products other than tenapanor or phosphate binders, active vitamin D and analogs, cinacalcet, calcitonin, and P-glycoprotein inhibitors
• Agreement to use highly effective contraception for women of childbearing potentially and non-sterile sexually active males throughout the study and for 90 days after the final dose of study drug

Important Exclusion Criteria:

• Pregnant or breastfeeding
• Scheduled for a living donor kidney transplant in the next 6 months, planned change to peritoneal dialysis or home hemodialysis in the study; planned relocation to another dialysis center in the study
• Any history of a non-pharmacological parathyroid intervention within 6 months prior to the ICF sign off, or planned parathyroid intervention in the study
• Blood calcium or blood intact parathyroid hormone abnormality
• Adequate organ and bone marrow function
• Acute hepatitis or significant chronic liver disease
• Any clinically significant GI disorders within 4 weeks prior to signing the ICF; or any history of gastrectomy; or any GI tract surgery (excluding appendectomy and polypectomy), within 12 weeks of signing the ICF
• Uncontrolled hypertension
• Hospitalization for cardiac or cardiocerebrovascular disease within 24 weeks prior to signing the ICF
• Significant abnormalities of QT interval and heart rhythm on an electrocardiograph (ECG) test
• Any clinically significant active infection or infestation or any treatment with systemic antimicrobial treatment within 2 weeks prior to signing the ICF
• History or presence of malignancy within 3 years prior to signing the ICF, except basal cell skin cancer, in-situ carcinoma of the cervix, and in-situ prostate cancer
• Taking moderate or strong cytochrome P450 (CYP) 3A inhibitors within 2 weeks or 5 half-lives, whichever is longer, prior to signing the ICF (topical use is allowed)
• Treatment with any investigational medication or medical device within 30 days prior to signing the ICF
• Life expectancy less than 12 months

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 24 centers

• Apogee Clinical Research, LLC — Huntsville
• California Institute of Renal Research — Chula Vista
• Academic Medical Research Institute — Los Angeles
• North America Research Institute — San Dimas
• Colorado Kidney Care — Denver
• DaVita Clinical Research — Middlebury
• PACT Kidney Care — Orange
• US Renal Care - Fort Myers South — Fort Myers
• … and 16 more centers

China · 7 centers

• Peking University First Hospital — Beijing
• Peking University People's Hospital — Beijing
• R1 Therapeutics Clinical Trial Site — Zhengzhou
• The Second Affiliated Hospital of Nanjing Medical University — Nanjing
• Zhongda Hospital Southeast University — Nanjing
• Shanghai Jiao Tong University School of Medicine, Renji Hospital — Shanghai
• Sichuan Provincial People's Hospital — Chengdu

Identifiers

NCT: NCT06712654 · AP306-HP-202

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗