E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of Hyperphosphataemia. |
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E.1.1.1 | Medical condition in easily understood language |
Hyperphosphataemia in chronic kidney disease is caused by decreased excretion of phosphorus by kidneys. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020712 |
E.1.2 | Term | Hyperphosphatemia |
E.1.2 | System Organ Class | 100000004861 |
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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 compare the percentage of subjects achieving age-specific Kidney Disease Outcomes Quality Initiative (KDOQI) targets for serum phosphorus in hyperphosphataemic children and adolescents with chronic kidney disease (CKD) on dialysis following treatment with calcium carbonate for 8 weeks and lanthanum carbonate for 8 weeks. |
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E.2.2 | Secondary objectives of the trial |
1. To compare mean changes from baseline in serum phosphorus,
calcium, and calcium-phosphorus product in hyperphosphataemic
children and adolescents with CKD who are on dialysis, following
treatment with calcium carbonate for 8 weeks and lanthanum carbonate
for 8 weeks.
2. To describe the pharmacokinetics (maximum plasma concentration
[Cmax] and area under the plasma concentration-time curve from time
zero to the time of the last quantifiable concentration [AUC0-t]; bodyweight-
normalised) of lanthanum carbonate in hyperphosphataemic
children and adolescents aged 10 years to <18 years with CKD who are
on dialysis, after a single dose of lanthanum carbonate oral powder
formulation is administered (Part 1 of the study).
3. To investigate the efficacy (serum phosphorus, calcium, and calciumphosphorus
product) and safety of 8 months of treatment with
lanthanum carbonate in children and adolescents aged 10 years to <18
years (Parts 2 and 3 of the study combined). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The subject cannot be enrolled in the study before all of the following
inclusion criteria(including test results) are met.
1.Aged 10 years to <18 years of age at the time of consent.
2. Subject or parent/legally authorised representative (LAR) understand
and are able,willing, and likely to fully comply with the study procedures
and restrictions defined in this protocol.
3.Male, or non-pregnant, non-lactating female who agrees to comply
with any applicable contraceptive requirements of the protocol.
4. Established CKD, on dialysis, and requires treatment for
hyperphosphataemia with a phosphate binder.
5. Serum phosphorus levels after a washout period of up to 3 weeks as
follows:
- Age <12 years: Serum phosphorus >6.0mg/dL (1.94mmol/L)
- Age 12 years and older: Serum phosphorus >5.5mg/dL (1.78mmol/L)
6. Ability to provide written, signed and dated (personally or via an LAR)
informed consent/and assent, as applicable, to participate in the study.
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E.4 | Principal exclusion criteria |
1. Current or recurrent disease (eg, cardiovascular, liver, unstable and
uncontrolled gastrointestinal, malignancy, or other conditions) other
than CKD or end-stage renal disease that could affect the action,
absorption, or disposition of the investigational product, or clinical or
laboratory assessments.
2. Current or relevant history of physical or psychiatric illness, any
medical disorder (except for CKD or end-stage renal disease and related
co-morbidities) that may require treatment or make the subject unlikely
to fully complete the study, or any condition that presents undue risk
from the investigational product or procedures.
3. Unable to eat solid or semi-solid foods or on Total Enteral
Alimentation.
4. Serum PTH >700pg/mL.
5. Known or suspected intolerance or hypersensitivity to the
investigational product(s), closely related compounds, or any of the
stated ingredients.
6. History of alcohol or other substance abuse within the last year.
7. Current use of any medication (including over-the-counter, herbal, or
homeopathic preparations) that could affect (improve or worsen) the
condition being studied, or could affect the action, absorption, or
disposition of the investigational product(s), or clinical or laboratory
assessment. (Current use is defined as use within 1 day.) See Section 5
(Prior and Concomitant Treatment) for a list of prohibited and restricted
medications.
8. Weight and age of subject are outside local applicable criteria for
blood sample volumelimits.
9. Use of another investigational product within 30 days prior to
receiving the first dose of investigational product. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The percentage of subjects with serum phosphorus levels below the age-specific KDOQI targets following 8-weeks of treatment with calcium carbonate and lanthanum carbonate (Part 2 of the study).
The KDOQI serum phosphorus targets are defined as:
‒ Adolescents aged ≥12-<18 years: ≤5.5mg/dL (1.78mmol/L).
‒ Children aged 6 months -<12 years: ≤6.0mg/dL (1.94mmol/L).
The null hypothesis is that the difference in the percentages of subjects below the age-specific KDOQI targets following treatment with lanthanum carbonate and treatment with calcium carbonate is ≤-15% and the alternative hypothesis is that the difference in the corresponding percentages is >-15%.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Change from baseline in serum phosphorus, calcium and calcium-phosphorus product levels at the last visit of each 8-week treatment period during Part 2 and monthly during the 10-month extension phase.
• Biochemical bone markers: bone ALP, osteocalcin, TRAP and FGF-23, PTH, sclerostin and fetuin-A before and after each treatment period in Part 2, and at the end of Part 3 (Visits 2.0, 2.4, 2.5, 2.8, and 3.9).
• Height or length, head circumference and weight at each visit.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
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 | No |
E.8.1.6 | Cross over | Yes |
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 | 1 |
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 | 12 |
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 |
Argentina |
Bulgaria |
Chile |
Czech Republic |
Germany |
Hungary |
Poland |
Romania |
Russian Federation |
Turkey |
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E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |