Control of hyperphosphataemia in patients with chronic kidney disease on dialysis MedDRA version: 14.0 Level: LLT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 10038359 - Renal and urinary disorders MedDRA version: 14.0 Level: PT Classification code 10020711 Term: Hyperphosphataemia System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Sponsors
Vifor (International) Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects receiving maintenance HD 3 times/week with a Kt/V of =1.2 or peritoneal dialysis (PD) with a Kt/V of =1.7 within the last 3 months prior to screening. No home HD or nocturnal HD (overnight stay at site) will be allowed. 2. Subjects with a history of hyperphosphataemia and receiving stable doses of a phosphate binder(s) for at least 1 month prior to screening. Subjects may be on stable doses of 1 or 2 phosphate binders. 3. Male and female adult subjects (aged =18 years at time of consent). 4. Subjects with serum phosphate levels =1.94 mmol/L (=6.0 mg/dL) during the washout period (a minimum of 2 weeks washout period is obligatory). 5. Subjects with the ability to understand the requirements of the study and abide by the study restrictions, and who agree to return for the required assessments, in the Investigator’s opinion. 6. Subjects (or their legally acceptable representative) who have provided the appropriate written informed consent. Subjects must provide written informed consent before any study-specific procedures are performed including screening procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 564 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 376
Exclusion criteria
Exclusion criteria: 1. Subjects with intact parathyroid hormone (iPTH) levels >800 ng/L (>800 pg/ml or 88 pmol/L) at screening. Subjects with iPTH >600 ng/L (>600 pg/ml or 66 pmol/L) at screening must be considered stable in the Investigator’s opinion. 2. Subjects with planned or expected parathyroidectomy within the next 12 months, in the Investigator’s opinion. 3. Subjects with anticipated need for major surgery during the study that may be associated with increased risk to the subject, or may interfere with study assessments or outcomes, or the ability to provide written informed consent or comply with study procedures, in the Investigator’s opinion. 4. Subjects with history (within 3 years of screening) of: - Major gastrointestinal surgery likely to influence the outcome of treatment with phosphate binders - Significant gastrointestinal or hepatic disorders 5. Subjects currently with, in the Investigator’s opinion: - Unstable angina - Unstable hypertension - Uncontrolled diabetes - Estimated life expectancy of less than 12 months - Anticipated renal transplantation during study participation 6. Subjects with known seropositivity to human immunodeficiency virus. 7. Subjects with hepatitis B surface antigen positivity and/or hepatitis C virus ribonucleic acid positivity at screening. 8. Subjects with significant medical conditions which, in the Investigator’s opinion, may be associated with increased risk to the subject, or may interfere with study assessments or outcomes, or the ability to provide informed consent or comply with study procedures. 9. Subjects with: - A history of haemochromatosis or other iron accumulation disturbances that might lead to iron overload - Serum ferritin >2,000 mcg/L (4,494 pmol/L) at screening 10. Subjects on PD with a history of peritonitis in the last 3 months or =3 episodes in the last 12 months. 11. Subjects on non-calcium based phosphate binders with hypercalcaemia (total serum calcium >2.60 mmol/L or >10.50 mg/dL) at screening. 12. Subjects with hypocalcaemia (total serum calcium 3 times the upper limit of the normal range at screening. 14. Subjects taking any prohibited medications (see Section 7.7, Prohibited Therapy and Concomitant Treatment, page 57). 15. Subjects taking more than 2 phosphate binders concomitantly prior to screening or subjects who are phosphate binder naïve prior to screening. 16. Subjects with a history of drug or alcohol abuse within 2 years before screening. 17. Subjects currently enrolled in or who have completed any other investigational device or drug study <30 days prior to screening, or subjects receiving other investigational agent(s). 18. Subjects who are pregnant (e.g., positive human chorionic gonadotropin test), breast feeding, or, if of child-bearing potential, are not using adequate contraceptive precautions. Subjects must agree to use adequate contraception during the study and for 1 month after the last dose of the study medication. Adequate methods of birth control are defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intra-uterine devices, sexual abstinence or vasectomised partner. Non child-bearing potential includes being surgically sterilised at least 6 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Establish the superiority of PA21-maintenance dose versus PA21-low dose control in maintaining the phosphate lowering effect in HD patients, by comparing the change in serum phosphate levels during a 3 week period that follows 24 weeks of PA21 treatment.;Secondary Objective: •Assess the long term safety and tolerability of PA21 in dialysis patients •Establish the non-inferiority (with possible assessment of superiority) of PA21 versus sevelamer carbonate in lowering serum phosphate in dialysis patients after 12 weeks of treatment •Assess Quality of Life •Compare safety and tolerability of PA21 versus sevelamer carbonate ;Primary end point(s): Primary Efficacy: •Change from Week 24, D1 in serum phosphate levels at Week 27, D1 – a superiority comparison between the PA21 maintenance dose group and the PA21 low dose control group (fixed dose of 1.25 g/day) (full analysis set (FAS)) (D1 refers to the first dialysis session of the week). Primary Safety: •Adverse events (AEs) profile and routine biochemical/haematological laboratory tests. ;Timepoint(s) of evaluation of this end point: Primary Efficacy - Week 27 Primary Safety - End of Study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Establish the non-inferiority (with possible assessment of superiority) of PA21 versus sevelamer carbonate in lowering serum phosphate in dialysis patients after 12 weeks of treatment •Assess Quality of Life •Compare safety and tolerability of PA21 versus sevelamer carbonate;Timepoint(s) of evaluation of this end point: End of Study | — |
Countries
Austria, Belgium, Croatia, Czech Republic, Germany, Latvia, Lithuania, Poland, Romania, Russian Federation, Serbia, South Africa, Sweden, Switzerland, Ukraine, United Kingdom, United States
Contacts
Public ContactMaxim Voropayev
Vifor (International) Inc.
Outcome results
None listed