E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Control of hyperphosphataemia in patients with chronic kidney disease on dialysis |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic Kidney disease patients on dialysis with hight phosphate |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064848 |
E.1.2 | Term | Chronic kidney disease |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020711 |
E.1.2 | Term | Hyperphosphataemia |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To Establish the superiority of PA21-maintenance dose versus PA21-low dose control in maintaining the phosphate lowering effect in haemodialysis (HD) patients after 24 weeks of PA21 treatment |
|
E.2.2 | Secondary objectives of the trial |
•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
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 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) at any time during the washout period.
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.
|
|
E.4 | Principal 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 active hepatitis (hepatitis B or C surface antigen positive).
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 <1.9 mmol/L or <7.6 mg/dL) at screening.
13.Subjects with raised alanine aminotransferase or aspartate aminotransferase >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 prior to the study or post menopausal, defined as amenorrhea for at least 12 months.
19.Subjects with a known sensitivity to any of the study products to be administered during dosing.
20.Subjects previously randomised to treatment in this or any other PA21 study.
21.Subjects with any kind of disorder that compromises the ability of the subject to give informed consent and/or to comply with study procedures.
|
|
E.5 End points |
E.5.1 | 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.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary Efficacy - Week 27 Primary Safety - End of Study |
|
E.5.2 | 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 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 69 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Belgium |
Croatia |
Czech Republic |
Germany |
Latvia |
Lithuania |
Poland |
Romania |
Russian Federation |
South Africa |
Sweden |
Switzerland |
Ukraine |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
last visit of the last subject undergoing the trial |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |