Safety and Efficacy of Paricalcitol Capsules in Decreasing Serum Parathyroid Hormone Levels in Children Aged 10-16 With Chronic Kidney Disease (CKD)
1 juin 2018 mis à jour par: AbbVie (prior sponsor, Abbott)
A Phase 3, Prospective, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Pharmacokinetics, Safety and Efficacy of Paricalcitol Capsules in Decreasing Serum Intact Parathyroid Hormone Levels in Pediatric Subjects Ages 10 to 16 Years With Moderate to Severe Chronic Kidney Disease
Part 1: To determine the safety, tolerability, and pharmacokinetics of a single dose of 3 μg paricalcitol capsules in children ages 10 to 16 years with moderate to severe chronic kidney disease (CKD Stages 3 and 4).
Part 2: To determine the safety and efficacy of paricalcitol capsules as compared to placebo in decreasing serum intact parathyroid hormone (iPTH) in children ages 10 to 16 years with moderate to severe chronic kidney disease with an initial 12 weeks of double-blinded study drug followed by a minimum of 12 weeks of open-label active drug.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
The study consists of two parts.
Part 1 is an open-label single-dose, non-fasting, multicenter study to evaluate the pharmacokinetics (PK) of paricalcitol capsules in 12 children ages 10 to 16 years with CKD Stages 3 and 4. Part 2 of this study will be conducted as a 12 week randomized double-blind, placebo-controlled study, followed by 12 weeks open-label treatment.
Participants active or enrolled under amendment 5 will enter a follow-up period and have study visits every 4 weeks until the final participant reaches Week 24.
Type d'étude
Interventionnel
Inscription (Réel)
47
Phase
- Phase 3
Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
10 ans à 16 ans (Enfant)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria:
- Subject has chronic kidney disease Stage 3 or 4 as determined by estimated glomerular filtration rate (15 to 59 mL/min/1.73 m²) at Screening.
- Subject is not expected to begin dialysis for at least 6 months (in the opinion of the investigator).
For entry into the Washout Period (for subjects who are currently on a vitamin D receptor activator [VDRA] and need to complete a 2 to 4 week washout), the subject must satisfy the following criteria based on the Screening laboratory values:
- estimated glomerular filtration rate between 15 to 59 mL/min/1.73 m².
- iPTH measurement that is greater than or equal to 60 pg/mL (Stage 3 subjects) or greater than or equal to 90 pg/mL (Stage 4 subjects).
- An adjusted serum calcium value greater than or equal to 8.2 mg/dL (2.05 mmol/L) to less than or equal to 10.5 mg/dL (2.63 mmol/L).
- A serum phosphorus value greater than or equal to 2.0 mg/dL (0.65 mmol/L but less than or equal to 6.0 mg/dL (1.94 mmol/L).
For entry into the Treatment Phase (vitamin D receptor activator naïve subjects and those that have completed a 4 week washout), the subject must have:
- iPTH measurement that is greater than or equal to 75 pg/mL (Stage 3 subjects) or greater than or equal to 110 pg/mL (Stage 4 subjects).
- An adjusted serum calcium value greater than or equal to 8.4 mg/dL (2.10 mmol/L) but less than or equal to 10.2 mg/dL (2.55 mmol/L).
- A serum phosphorus value greater than or equal to 2.5 mg/dL (0.81 mmol/L) but less than or equal to 5.8 mg/dL (1.87 mmol/L).
- Must have 25-hydroxyvitamin D levels ≥ 30 ng/mL prior to washout, if not VDRA naïve, or treatment in Part II of the study.
Exclusion Criteria:
- All subjects that have had a small bowel transplant will be excluded from the study.
- Subject has had acute kidney failure within 12 weeks of the Screening Phase (defined as an acute rise in serum creatinine).
- Subject has had symptomatic or significant hypocalcemia requiring active vitamin D therapy (for example, calcitriol, paricalcitol, doxercalciferol or alfacalcidol) within 6 months prior to the Screening Phase.
- Subject has a history of active kidney stones (6 months prior to screening).
- Subject has chronic gastrointestinal disease, which in the investigator's opinion may cause significant gastrointestinal malabsorption.
- Subject is taking maintenance calcitonin, bisphosphonates, cinacalcet, glucocorticoids in an equivalent dose of greater than 5 mg prednisone daily, or other drugs known to affect calcium or bone metabolism within 4 weeks prior to treatment.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Double
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: Part 1: Paricalcitol
Participants received a single 3 µg dose of paricalcitol capsules on Study Day 1.
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Paricalcitol capsules taken with water.
Autres noms:
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Comparateur placebo: Part 2: Placebo
Participants received placebo capsules three times a week (TIW) for 12 weeks during the double-blind treatment phase.
From Weeks 12 to 24 participants received open-label paricalcitol at an initial dose of 1 µg three times a week.
Doses could be increased in 1 μg increments every 4 weeks based on chemistry evaluations to target Kidney Disease Outcomes Quality Initiatives (KDOQI) target levels.
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Paricalcitol capsules taken with water.
Autres noms:
Placebo capsules taken with water
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Expérimental: Part 2: Paricalcitol
Participants received paricalcitol three times a week for 12 weeks during the double-blind treatment period and during the open-label period (Weeks 12-24).
The initial dose of paricalcitol was 1 µg TIW.
Doses could be increased in 1 μg increments every 4 weeks based on chemistry evaluations to target KDOQI target levels.
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Paricalcitol capsules taken with water.
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Part 1: Paricalcitol Maximum Observed Plasma Concentration (Cmax)
Délai: Blood samples were collected at hour 0, 1, 2, 4, 6, 8, 12, 24, 36, and 48 hours after dosing.
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Blood samples were collected at hour 0, 1, 2, 4, 6, 8, 12, 24, 36, and 48 hours after dosing.
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Part 1: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞)
Délai: Blood samples were collected at hour 0, 1, 2, 4, 6, 8, 12, 24, 36, and 48 hours after dosing.
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Blood samples were collected at hour 0, 1, 2, 4, 6, 8, 12, 24, 36, and 48 hours after dosing.
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Part 2: Percentage of Participants Achieving Two Consecutive Reductions at Least 30% From Baseline in iPTH
Délai: 12-week double-blind treatment period
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The primary efficacy endpoint was the percentage of participants who achieved two consecutive ≥ 30% reductions from baseline in intact parathyroid hormone (iPTH) levels during the 12 week double-blind portion of the study regardless of CKD stage.
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12-week double-blind treatment period
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Part 2: Percentage of Participants Achieving a Final iPTH Within KDOQI Target Ranges
Délai: Week 12
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The Kidney Disease Outcomes Quality Initiatives (KDOQI) Pediatric Subcommittee on Practice Guidelines for Bone Metabolism and Disease in Children with CKD target range for intact parathyroid hormone (iPTH) is as follows:: CKD Stage 3: 35 - 69 pg/mL; CKD Stage 4: 70 - 110 pg/mL. |
Week 12
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Part 2: Change From Baseline in iPTH to Each Post-baseline Visit
Délai: Baseline and Weeks 2, 4, 8 and 12
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Baseline and Weeks 2, 4, 8 and 12
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Part 2: Percentage of Participants Achieving Final Calcium Levels Within KDOQI Target Ranges
Délai: Week 12
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KDOQI recommends serum calcium is maintained within age appropriate normal ranges: Age 6 - 12: 9.4 - 10.2 mg/dL (2.35 - 2.55 mmol/L); Age 13 - 20: 8.8 - 10.2 mg/dL (2.20 - 2.55 mmol/L). |
Week 12
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Part 2: Percentage of Participants Achieving Final Phosphorus Levels Within KDOQI Target Ranges
Délai: Week 12
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The KDOQI target ranges of serum phosphorus are to maintain at or above age appropriate lower limits and no higher than the age-appropriate upper limits: Age 6 - 12: 3.6 - 5.8 mg/dL (1.16 - 1.87 mmol/L); Age 13 - 20: 2.3 - 4.5 mg/dL (0.74 - 1.45 mmol/L). |
Week 12
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Part 2: Change From Baseline in First Morning Void (FMV) Urinary Albumin to Creatinine Ratio (UACR)
Délai: Baseline and Weeks 4, 8 and 12
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The mean change from Baseline in FMV UACR on a log scale to each post baseline visit.
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Baseline and Weeks 4, 8 and 12
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Les enquêteurs
- Directeur d'études: Deepa Chand, MD, AbbVie
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Liens utiles
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 février 2010
Achèvement primaire (Réel)
1 mai 2014
Achèvement de l'étude (Réel)
1 décembre 2014
Dates d'inscription aux études
Première soumission
13 novembre 2009
Première soumission répondant aux critères de contrôle qualité
20 novembre 2009
Première publication (Estimation)
24 novembre 2009
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
2 juillet 2018
Dernière mise à jour soumise répondant aux critères de contrôle qualité
1 juin 2018
Dernière vérification
1 février 2017
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- M10-149
- 2010-019439-37 (Numéro EudraCT)
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