E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of Hyperphosphataemia. |
|
E.1.1.1 | Medical condition in easily understood language |
Hyperphosphataemia in chronic kidney disease is caused by decreased
excretion of phosphorus by kidneys. |
|
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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020712 |
E.1.2 | Term | Hyperphosphatemia |
E.1.2 | System Organ Class | 100000004861 |
|
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. |
|
E.2.2 | Secondary objectives of the trial |
Compare mean changes from baseline in hyperphosphataemic
children/adolescents with CKD on dialysis following treatment with
calcium carbonate for 8 weeks & lanthanum carbonate for 8 weeks.
Describe pharmacokinetics (PK) of lanthanum carbonate in
hyperphosphataemic children/adolescents aged 6 months to <18 years
with CKD on dialysis after a single dose of lanthanum carbonate oral
powder formulation is administered (Part 1).
Investigate efficacy & safety of 12 months treatment with lanthanum
carbonate in children/adolescents aged 6 months to <18 years (Part 2
and 3).
Investigate biochemical markers of bone metabolism in
children/adolescents aged 6 months to <18 years with CKD on dialysis.
Investigate growth in children/adolescents aged 6 months to <18 years
with CKD on dialysis.
Investigate safety profile in hyperphosphataemic children/adolescents
with CKD on dialysis treated with calcium carbonate & lanthanum
carbonate. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects 6 months to less than 18 years of age at the time of consent.
2. Established on solid food, i.e., not exclusively on a liquid diet.
3. Subject and parent or LAR understand and are able, willing, and likely
to fully comply with the study procedures and restrictions defined in this
protocol.
4. Male, or non pregnant, non lactating female who agrees to comply
with any applicable contraceptive requirements of the protocol.
5. Established CKD on dialysis and requires treatment for
hyperphosphataemia with a phosphate binder.
6. Serum phosphorus levels after a washout period of up to 3 weeks:
• Age <12 years: Serum phosphorus > 6.0mg/dL (1.94mmol/L).
• Age 12 years and older: Serum phosphorus >5.5mg/dL
(1.78mmol/L).
7. Ability to provide written, signed, and dated (personally or via a
legally acceptable representative) informed consent/and assent, as
applicable, to participate in the study. |
|
E.4 | Principal exclusion criteria |
Subjects are excluded from the study if any of the following criteria are
met:
1. Current or recurrent disease (e.g., cardiovascular, liver, unstable and
uncontrolled gastrointestinal (GI), malignancy, or other conditions)
other than CKD or ESRD 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 ESRD 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 semi-solid foods or on Total Enteral Alimentation.
4. Serum PTH > 700pg/mL.
5. Serum calcium >10.2mg/dL (2.54mmol/L).
6. Known or suspected intolerance or hypersensitivity to the
investigational product(s), closely related compounds, or any of the
stated ingredients.
7. History of alcohol or other substance abuse within the last year.
8. Current use of any medication (including over-the-counter (OTC),
herbal, or homeopathic preparations) that could affect (improve or
XML File Identifier: hP7Yn8dAnvD9kP63iuuLx7HP2NM=
Page 15/26
worsen) the condition being studied, or could affect the action,
absorption, or disposition of the investigational product(s), or clinical or
laboratory assessment.
9. Weight and age of subject are outside local applicable criteria for
blood sample volume limits.
10. Use of another investigational product within 30 days prior to
receiving the first dose of investigational product.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The percentage of subjects with serum phosphorus levels below the agespecific
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%. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Change from baseline in serum phosphorus, calcium and calciumphosphorus
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, 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, 2.8, and 3.9).
• Height or length, head circumference and weight at each visit. |
|
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 | 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 |
|
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 | 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 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Argentina |
Chile |
Germany |
Hungary |
India |
Poland |
Russian Federation |
South Africa |
Turkey |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
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 |