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 |
Patients with chhronic kidney disease on dialysis with high phosphate levels |
|
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 | LLT |
E.1.2 | Classification code | 10020712 |
E.1.2 | Term | Hyperphosphatemia |
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 assess the long-term safety and tolerability of PA21 |
|
E.2.2 | Secondary objectives of the trial |
To compare the long-term serum phosphate control of PA21 versus sevelamer
carbonate
To compare the safety and tolerability of PA21 versus sevelamer carbonate |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects who have completed treatment in Protocol PA-CL-05A (Stage 1
or Stage 2) (except subjects randomised to the PA21 low dose group of the
Stage 2 primary efficacy assessment).
2. 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 randomised to the PA21 low dose group of the Stage 2 primary
efficacy assessment of Protocol PA-CL-05A.
2. Subjects with hypercalcaemia (total serum calcium >2.75 mmol/L or
>11.00 mg/dL at the previous study visit in Protocol PA-CL-05A
(Week 20 for Stage 1, Week 26 for Stage 2)) (central laboratory values).
3. Subjects with hypocalcaemia (total serum calcium <1.9 mmol/L or
<7.6 mg/dL at the previous study visit in Protocol PA-CL-05A (Week 20
for Stage 1, Week 26 for Stage 2)) (central laboratory values).
4. Subjects with raised alanine aminotransferase or aspartate
aminotransferase >3 times the upper limit of the normal range at the
previous study visit in Protocol PA-CL-05A (Week 20 for Stage 1,
Week 24 for Stage 2) (central laboratory values).
5. Subjects taking any prohibited medications (see Section 7.7, Prohibited
Therapy and Concomitant Treatment, page 41).
6. Subjects who are pregnant (e.g., positive human chorionic gonadotropin
test at Week 20 Protocol PA-CL-05A), breast feeding or, if of childbearing
potential, 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-childbearing potential includes being surgically sterilised at least
6 months prior to the study or post-menopausal, defined as amenorrhea for
at least 12 months.
7. Subjects with serum ferritin >2,000 mcg/L (>4.494 pmol/L) at the previous study visit in Protocol PA-CL-05A (Week 20 for Stage 1, Week 24 for Stage 2) (central laboratory values).
8. Subjects with any kind of disorder that compromises the ability of the
subject to give written informed consent and/or to comply with study
procedures. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Adverse events (AE) profile and routine biochemical/haematological
laboratory tests |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
•Comparison of the AE profiles of PA21 and sevelamer carbonate subjects
•Serum calcium (total, corrected and ionised) at each time point and change from entry into Protocol PA-CL-05B
•Percentage of subjects that develop at least 1 episode of sustained hypercalcaemia (total serum calcium >2.75 mmol/L or >11.00 mg/dL)
during study participation (confirmed by repeat sample 1 week later), despite "rescue" interventions
•Serum calcium x phosphate product at each time point and change from entry into Protocol PA-CL-05B
•Serum intact parathyroid hormone levels at each time point and change from entry into Protocol PA-CL-05B
•Biochemical (including liver function tests) and haematological laboratory tests
•Iron status: iron, ferritin, transferrin and transferrin saturation
•Biochemical markers of bone resorption and formation
• Vitamin status (A, D, E and K) |
|
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 3 |
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 |
Serbia |
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
|
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |