A Study to Assess the Pharmacokinetics of Lanthanum Carbonate, Investigate and Compare the Efficacy, Safety and Tolerability of Lanthanum Carbonate With Calcium Carbonate in Hyperphosphataemic Children and Adolescents With Chronic Kidney Disease on Dialysis

Study Overview
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Brief Summary
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The purpose of this study is to summarize the percentage of participants achieving age-specific Kidney Disease Outcomes Quality Initiative (KDOQI) targets for serum phosphorus in hyperphosphatemic children and adolescents with chronic kidney disease (CKD) who are on dialysis, following 8 weeks of treatment with lanthanum carbonate.

Official Title
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A 3-part Open-label Study to Assess the Pharmacokinetics of Lanthanum Carbonate, Compare the Efficacy, Safety and Tolerability of 8 Weeks of Treatment With Lanthanum Carbonate and Calcium Carbonate Using a Crossover Design and Investigate the Efficacy and Safety of 8 Months of Treatment With Lanthanum Carbonate in Hyperphosphataemic Children and Adolescents Aged 10 Years to <18 Years With Chronic Kidney Disease on Dialysis

Conditions
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Chronic Kidney Disease, Hyperphosphatemia

Intervention / Treatment
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* Drug: Lanthanum Carbonate
* Drug: Calcium Carbonate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 10 years to less than (<) 18 years of age at the time of consent. Participant or parent/legally authorized representative (LAR) understand and are able, willing, and likely to fully comply with the study procedures and restrictions defined in this protocol. Male, or non-pregnant, non-lactating female who agrees to comply with any applicable contraceptive requirements of the protocol. Established chronic kidney disease (CKD), on dialysis, and requires treatment for hyperphosphatemia with a phosphate binder. Serum phosphorus levels after a washout period of up to 3 weeks as follows: Age <12 years: Serum phosphorus greater than (>) 6.0 mg/dL (1.94 mmol/L); Age 12 years and older: Serum phosphorus >5.5mg/dL (1.78mmol/L). Ability to provide written, signed and dated (personally or via an LAR) informed consent/and assent, as applicable, to participate in the study. Exclusion Criteria: Current or recurrent disease (example [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. 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 participant unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures. Unable to eat semi-solid foods or on Total Enteral Alimentation. Known or suspected intolerance or hypersensitivity to the investigational product(s), closely related compounds, or any of the stated ingredients. History of alcohol or other substance abuse within the last year. 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. Weight and age of participant are outside of local applicable criteria for blood sample volume limits. Use of another investigational product within 30 days prior to receiving the first dose of investigational product.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lanthanum Carbonate<br>Participants will receive lanthanum carbonate orally at a total daily dose of 1500 mg to 3000 mg divided and mixed equally between in three meals. | Drug: Lanthanum Carbonate<br>* Lanthanum Carbonate 1500 mg to 3000 mg powder will be administered orally.<br>* Other names: SPD405;|
| Active Comparator: Calcium Carbonate<br>Participants will receive calcium carbonate orally at a total daily dose adjusted as appropriate, until the target serum phosphorus level is achieved or until a maximum daily dose of 6500 mg is reached. | Drug: Calcium Carbonate<br>* Calcium carbonate will be administered orally at a total daily dose based on standard clinical practice. The total daily dose may be adjusted as appropriate, until the target serum phosphorus level is achieved or until a maximum daily dose of 6500 mg is reached.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Age-Specific Kidney Disease Outcomes Quality Initiative (KDOQI) Targets for Serum Phosphate Level Following 8 Weeks of Lanthanum Carbonate Administration (Part 2 + Part 3) | KDOQI serum phosphorus targets were defined for: Adolescents aged greater than or equal to (>=) 12 to less than (<) 18 years to be less than or equal to (<=) 5.5 milligrams per deciliter (mg/dL) (1.78 millimoles per liter [mmol/L]); Children aged >=10 years to <12 years to be <= 6.0 mg/dL (1.94 mmol/L). Percentage of participants achieving age-specific KDOQI targets for serum phosphate level was reported only for the participants who had received lanthanum carbonate during part 2 or part 3. Data was analyzed and presented as per the intervention received in this study related to this outcome and not analyzed based on each part of the study. | After 8 weeks of lanthanum carbonate administration in Part 2 and/or in Part 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Age-Specific Kidney Disease Outcomes Quality Initiative (KDOQI) Targets for Serum Phosphate Level During Part 2 | KDOQI serum phosphorus targets was defined for: Adolescents aged >= 12 < 18 years to be <= 5.5 mg/dL (1.78 [mmol/L]); Children aged >=10 years to <12 years to be <= 6.0 mg/dL (1.94 mmol/L). Percentage of participants achieving age-specific KDOQI targets for serum phosphate level were reported only for the participants who had received calcium carbonate followed by 8 weeks of treatment with lanthanum carbonate in Part 2. Data was analyzed and presented as per the intervention received in this study related to this outcome and not analyzed based on each part of the study. | Up to 19 weeks | 
| Change From Baseline in Serum Phosphorus Levels Following Treatment With Lanthanum Carbonate After 8 Weeks | Changes from baseline in serum phosphorus levels in hyperphosphatemic children and adolescents with chronic kidney disease (CKD) who are on dialysis, following treatment with lanthanum carbonate for 8 weeks were combined and reported. Baseline was defined as the last assessment prior to the first dose of investigational product. Data was analyzed and presented as per the intervention received in this study related to this outcome and not analyzed based on each part of the study. | Baseline, Week 8 of lanthanum carbonate administration in Part 2 and/or in Part 3 | 
| Change From Baseline in Calcium Levels Following Treatment With Lanthanum Carbonate After Week 8 | Changes from baseline in calcium levels in hyperphosphatemic children and adolescents with CKD who are on dialysis, following treatment with lanthanum carbonate for 8 weeks were combined and reported. Baseline was defined as the last assessment prior to the first dose of investigational product. Data was analyzed and presented as per the intervention received in this study related to this outcome and not analyzed based on each part of the study. | Baseline, Week 8 of lanthanum carbonate administration in Part 2 and/or in Part 3 | 
| Change From Baseline in Calcium-Phosphorus Product Levels Following Treatment With Lanthanum Carbonate After Week 8 | Changes from baseline in calcium-phosphorus product levels in hyperphosphatemic children and adolescents with CKD who are on dialysis, following treatment with lanthanum carbonate for 8 weeks were combined and reported. Baseline was defined as the last assessment prior to the first dose of investigational product. The unit of measure for this outcome measure was millimole square per square liter (mmol^2/L^2). Data was analyzed and presented as per the intervention received in this study related to this outcome and not analyzed based on each part of the study. | Baseline, Week 8 of lanthanum carbonate administration in Part 2 and/or in Part 3 | 
| Change From Baseline in Serum Phosphorus Levels Following Treatment With Calcium Carbonate After 8 Weeks and Lanthanum Carbonate After 8 Weeks During Part 2 | Changes from baseline in serum phosphorus levels in hyperphosphatemic children and adolescents with CKD who are on dialysis, following treatment with calcium carbonate after 8 weeks and lanthanum carbonate after 8 weeks were combined and reported. Baseline was defined as the last assessment prior to the first dose of investigational product. Here, number of participants analyzed refers to the number of participants evaluable for this outcome at specified time point. Data was analyzed and presented as per the intervention received in this study related to this outcome and not analyzed based on each part of the study. | Baseline, Week 8 | 
| Change From Baseline in Calcium Levels Following Treatment With Calcium Carbonate After 8 Weeks and Lanthanum Carbonate After 8 Weeks During Part 2 | Changes from baseline in calcium levels in hyperphosphatemic children and adolescents with CKD who are on dialysis, following treatment with calcium carbonate after 8 weeks and lanthanum carbonate after 8 weeks were combined and reported. Baseline was defined as the last assessment prior to the first dose of investigational product. Here, number of participants analyzed refers to the number of participants evaluable for this outcome at specified time point. Data was analyzed and presented as per the intervention received in this study related to this outcome and not analyzed based on each part of the study. | Baseline, Week 8 | 
| Change From Baseline in Calcium-Phosphorus Product Levels Following Treatment With Calcium Carbonate After 8 Weeks and Lanthanum Carbonate After 8 Weeks During Part 2 | Changes from baseline in calcium-phosphorus product levels in hyperphosphatemic children and adolescents with CKD who are on dialysis, following treatment with calcium carbonate after 8 weeks and lanthanum carbonate after 8 weeks were combined and reported. Baseline was defined as the last assessment prior to the first dose of investigational product. The unit of measure for this outcome was millimole square per square liter. Here, number of participants analyzed refers to the number of participants evaluable for this outcome at specified time point. Data was analyzed and presented as per the intervention received in this study related to this outcome and not analyzed based on each part of the study. | Baseline, Week 8 | 
| Change From Baseline in Serum Phosphorus Levels at the Last Visit of 8-Week Treatment Period in Part 2 and Monthly During 6-Month Extension Phase of Part 3 | Change from baseline in serum phosphorus levels at the last visit of each 8-week treatment period during Part 2 and monthly during the 6-month extension phase (Part 3) were reported. Baseline was defined as the last assessment prior to the first dose of investigational product. Here, number of participants analyzed refers to the number of participants evaluable for this outcome at specified time point. Data was analyzed and presented as per the intervention received in this study related to this outcome and not analyzed based on each part of the study. | Baseline, Week 8, 12, 16, 20, 24, 28 and Week 32 | 
| Change From Baseline in Calcium Levels at the Last Visit of 8-Week Treatment Period in Part 2 and Monthly During 6-Month Extension Phase of Part 3 | Change from baseline in calcium levels at the last visit of each 8-week treatment period during Part 2 and monthly during the 6- month extension phase (Part 3) were reported.Baseline was defined as the last assessment prior to the first dose of investigational product. Here, number of participants analyzed refers to the number of participants evaluable for this outcome at specified time point. Data was analyzed and presented as per the intervention received in this study related to this outcome and not analyzed based on each part of the study. | Baseline, Week 8, 12, 16, 20, 24, 28 and Week 32 | 
| Change From Baseline in Calcium-Phosphorus Product Levels at the Last Visit of 8-Week Treatment Period in Part 2 and Monthly During 6-Month Extension Phase of Part 3 | Change from baseline in calcium-phosphorus product levels at the last visit of each 8-week treatment period during Part 2 and monthly during the 6-month extension phase (Part 3) were reported. Baseline was defined as the last assessment prior to the first dose of investigational product. Here, number of participants analyzed refers to the number of participants evaluable for this outcome at specified time point. The unit of measure of this outcome was millimole square per square liter. Data was analyzed and presented as per the intervention received in this study related to this outcome and not analyzed based on each part of the study. | Baseline, Week 8, 12, 16, 20, 24, 28 and Week 32 | 
| Change From Baseline in Biochemical Bone Markers | Change from baseline in bone turnover markers including bone alkaline phosphatase (ALP), osteocalcin, and sclerostin was reported for combined Part 2 and 3. End of the study (EOS) was defined as the completion if the participants benefited from and desired to continue dosing with lanthanum. Here, number of participants analyzed refers to the number of participants evaluable for this outcome at specified time point. Data was analyzed and presented as per the intervention received in this study related to this outcome and not analyzed based on each part of the study. | Baseline, Week 8, Week 16 and EOS (up to 42 weeks) | 
| Change From Baseline in Biochemical Bone Markers for Tartrate-Resistant Acid Phosphatase (TRAP) | Change from baseline in bone turnover markers for, tartrate-resistant acid phosphatase (TRAP) was reported for combined Part 2 and 3. End of the study was defined as the completion if the participants benefited from and desired to continue dosing with lanthanum. Here, number of participants analyzed refers to the number of participants evaluable for this outcome at specified time point. Data was analyzed and presented as per the intervention received in this study related to this outcome and not analyzed based on each part of the study. | Baseline, Week 8, Week 16 and EOS (up to 42 weeks) | 
| Change From Baseline in Biochemical Bone Markers for Fibroblast Growth Factor 23 (FGF-23) | Change from baseline in bone turnover markers including fibroblast growth factor 23 (FGF-23) was reported for combined Part 2 and 3. End of the study was defined as the completion if the participants benefited from and desired to continue dosing with lanthanum. Here, number of participants analyzed refers to the number of participants evaluable for this outcome at specified time point. Data was analyzed and presented as per the intervention received in this study related to this outcome and not analyzed based on each part of the study. | Baseline, Week 8, Week 16 and EOS (up to 42 weeks) | 
| Change From Baseline in Biochemical Bone Markers for Parathyroid Hormone (PTH) | Change from baseline in bone turnover markers for parathyroid hormone was reported for combined Part 2 and 3. End of the study is the completion if the participants benefited from and desired to continue dosing with lanthanum. Here, number of participants analyzed refers to the number of participants evaluable for this outcome at specified time point. Data was analyzed and presented as per the intervention received in this study related to this outcome and not analyzed based on each part of the study. | Baseline, Week 8, Week 16 and EOS (up to 42 weeks) | 
| Change From Baseline in Biochemical Bone Markers for Fetuin-A | Change from baseline in bone turnover markers for fetuin-A was reported for combined Part 2 and 3. End of the study is the completion if the participants has benefited from and desires to continue dosing with lanthanum. Here, number of participants analyzed refers to the number of participants evaluable for this outcome at specified time point. Data was analyzed and presented as per the intervention received in this study related to this outcome and not analyzed based on each part of the study. | Baseline, Week 8, Week 16 and EOS (up to 42 weeks) | 
| Change From Baseline in Height | Change from baseline in height for combined Part 2 and Part 3 for each drug at Week 8, 16 and end of study was reported. End of the study was defined as the completion if the participants benefited from and desired to continue dosing with lanthanum. Here, number of participants analyzed refers to the number of participants evaluable for this outcome at specified time point. Data was analyzed and presented as per the intervention received in this study related to this outcome and not analyzed based on each part of the study. | Baseline, Week 8, Week 16, and EOS (up to 42 weeks) | 
| Change From Baseline in Weight | Change from baseline in weight for combined Part 2 and Part 3 for each drug at Week 8, 16 and end of study was reported. End of the study was defined as the completion if the participants benefited from and desired to continue dosing with lanthanum. Here, number of participants analyzed refers to the number of participants evaluable for this outcome at specified time point. Data was analyzed and presented as per the intervention received in this study related to this outcome and not analyzed based on each part of the study. | Baseline, Week 8, Week 16, and EOS (up to 42 weeks) |