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Trial record 17 of 120 for:    Polycystic Kidney Disease

Safety, Pharmacokinetics, Tolerability and Efficacy of Tolvaptan in Children and Adolescents With ADPKD (Autosomal Dominant Polycystic Kidney Disease)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT02964273
First received: September 15, 2016
Last updated: November 10, 2016
Last verified: November 2016
  Purpose
The primary objective of the study is to assess the long term safety of treatment with tolvaptan in children and adolescents with autosomal dominant polycystic kidney disease (ADPKD). The secondary objective is to assess the pharmacodynamics, pharmacokinetics, and efficacy of tolvaptan in the same subject population.

Condition Intervention Phase
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Drug: Tolvaptan
Drug: Matching Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3b, Two-part, Multicenter, One Year Randomized, Double-blind, Placebo-controlled Trial of the Safety, Pharmacokinetics, Tolerability, and Efficacy of Tolvaptan Followed by a Two Year Open-label Extension in Children and Adolescent Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Resource links provided by NLM:


Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:
  • Change from baseline in spot urine osmolality (pre-morning dose) [ Time Frame: After 1 week of daily dosing during Phase A ] [ Designated as safety issue: No ]
  • Change from baseline in specific gravity (pre-morning dose) [ Time Frame: After 1 week of daily dosing during Phase A ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percent change from Phase A baseline in height-adjusted total kidney volume (htTKV) as measured by MRI [ Time Frame: at 12 months ] [ Designated as safety issue: No ]
  • 24-hour urine volume in mL [ Time Frame: After at least 1 month on study medication during Phase A ] [ Designated as safety issue: No ]
  • 24-hour fluid intake in mL [ Time Frame: After at least 1 month on study medication during Phase A ] [ Designated as safety issue: No ]
  • 24-hour fluid balance in mL [ Time Frame: After at least 1 month on study medication during Phase A ] [ Designated as safety issue: No ]
  • 24-hour fluid balance in mL [ Time Frame: At Week 1 during Phase A and Phase B ] [ Designated as safety issue: No ]
  • Change from baseline in renal function (eGFR by Schwartz formula) at each visit in Phase A [ Time Frame: At Week 1, Month 1, Month 6, Month 12 ] [ Designated as safety issue: No ]
  • Change from Phase B baseline in renal function (eGFR by Schwartz formula) [ Time Frame: At Week 1, Months 1, 6, 12, 18, 24 ] [ Designated as safety issue: No ]
  • Percent change from Phase B baseline in htTKV as measured by MRI [ Time Frame: at 12 months ] [ Designated as safety issue: No ]
  • Percent change from Phase B baseline in htTKV as measured by MRI [ Time Frame: at 24 months ] [ Designated as safety issue: No ]
  • Proportions of each Tanner Stage by gender compared to normative populations [ Time Frame: At baseline, 6 and 12 months during the placebo-controlled phase (Phase A) and every 6 months (up to 26, 52, 78 and 104 weeks) during the open-label extension (Phase B) ] [ Designated as safety issue: Yes ]
  • Proportions of each Tanner Stage by age compared to normative populations [ Time Frame: At baseline, 6 and 12 months during the placebo-controlled phase (Phase A) and every 6 months (up to 26, 52, 78 and 104 weeks) during the open-label extension (Phase B) ] [ Designated as safety issue: Yes ]
  • Description of changes from baseline for height in cm by gender and age [ Time Frame: at baseline, 6 and 12 months during the placebo-controlled phase (Phase A) and every 6 months (up to 26, 52, 78 and 104 weeks) during the open-label extension (Phase B) ] [ Designated as safety issue: Yes ]
  • Description of changes from baseline for weight in kilograms by gender and age [ Time Frame: at baseline, 6 and 12 months during the placebo-controlled phase (Phase A) and every 6 months (up to 26, 52, 78 and 104 weeks) during the open-label extension (Phase B) ] [ Designated as safety issue: Yes ]
  • Changes from baseline in creatinine [ Time Frame: up thru 14 days post last dose in Phase A or B, whichever completion is latter. ] [ Designated as safety issue: Yes ]
  • Changes from baseline in vital signs [ Time Frame: up thru 14 days post last dose in Phase A or B, whichever completion is latter. ] [ Designated as safety issue: Yes ]
  • Changes from baseline in liver function tests (LFTs) [ Time Frame: up thru 14 days post last dose in Phase A or B, whichever completion is latter. ] [ Designated as safety issue: Yes ]
  • Changes from baseline in rate of aquaretic AEs in placebo and tolvaptan [ Time Frame: up thru 14 days post last dose in Phase A or B, whichever completion is latter. ] [ Designated as safety issue: Yes ]
  • Pharmacodynamic (PD) endpoints of sodium, creatinine and free water clearances in mL/min [ Time Frame: After at least 1 month on study medication in Phase A ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: September 2016
Estimated Study Completion Date: October 2020
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Active Tolvaptan

In Phase A, subjects will be randomized in a 1:1 ratio to receive IMP (active tolvaptan or matching placebo) for 12 months.

Starting doses, if receiving active tolvaptan, are based on weight:

  • ≥ 20 kg to < 45 kg, 15/7.5 mg tolvaptan (TLV) split-dose
  • ≥ 45 kg to ≤ 75 kg, 30/15 mg TLV split-dose
  • > 75 kg, 45/15 mg TLV split-dose

After 1 week, subjects will be asked to uptitrate once from their starting dose of active tolvaptan.

  • ≥ 20 kg to < 45 kg, 30/15 mg TLV split-dose
  • ≥ 45 kg to ≤ 75 kg, 45/15 mg TLV split-dose
  • > 75 kg, 60/30 mg TLV split-dose

Qualified subjects who Complete Phase A are eligible to participate in Phase B.

Drug: Tolvaptan

Tolvaptan 7.5, 15, and 30 mg spray-dried, immediate release tablets with matching placebo. Subjects will be randomized to receive either active tolvaptan or matching placebo for 12 months in Phase A, followed by open-label tolvaptan for 24 months in Phase B. Study medication will be administered orally as a split-dose, with the first dose taken upon awakening and the second dose taken approximately 8 hours later. Phase A and Phase B starting doses will be based on weight. After 1 week, subjects will be asked to up-titrate once from their starting dose. Subjects may down-titrate at any time during the trial; however, subjects will be asked to stay on the highest tolerable dose (by weight group) if possible. The titration schedules for Phase A and Phase B are similar.

Frequency: Twice daily.

Other Name: JINARC®
Placebo Comparator: Matching Placebo

In Phase A, subjects will be randomized in a 1:1 ratio to receive IMP (active tolvaptan or matching placebo) for 12 months.

Starting doses are based on weight:

  • ≥ 20 kg to < 45 kg, 15/7.5 mg matching placebo split-dose
  • ≥ 45 kg to ≤ 75 kg, 30/15 mg matching placebo split-dose
  • > 75 kg, 45/15 mg matching placebo split-dose

After 1 week, subjects will be asked to uptitrate once from their starting dose of matching placebo.

  • ≥ 20 kg to < 45 kg, 30/15 mg matching placebo split-dose
  • ≥ 45 kg to ≤ 75 kg, 45/15 mg matching placebo split-dose
  • > 75 kg, 60/30 mg matching placebo split-dose Qualified subjects who Complete Phase A are eligible to participate in Phase B.
Drug: Matching Placebo

Placebo matching Tolvaptan 7.5, 15, and 30 mg spray-dried, immediate release tablets. Subjects will be randomized to receive either active tolvaptan or matching placebo for 12 months in Phase A, followed by open-label tolvaptan for 24 months in Phase B. Study medication will be administered orally as a split-dose, with the first dose taken upon awakening and the second dose taken approximately 8 hours later. Phase A and Phase B starting doses will be based on weight. After 1 week, subjects will be asked to up-titrate once from their starting dose. Subjects may down-titrate at any time during the trial; however, subjects will be asked to stay on the highest tolerable dose (by weight group) if possible. The titration schedules for Phase A and Phase B are similar.

Frequency: Twice daily.


Detailed Description:

Tolvaptan has been demonstrated to delay the decline of kidney function in adults with rapidly progressing ADPKD (CKD stages 1 to 3) as measured by estimated glomerular filtration rate (eGFR) and Total Kidney Volume (TKV).

This trial will be the first trial of tolvaptan in children and adolescents with ADPKD.

Subjects in this study will be randomly assigned to one of two groups in Phase A; tolvaptan or placebo. Participants will have an equal chance of being assigned to either treatment group and will be stratified by age and gender into the following cohorts:

  • Female subjects ages 12 to 14 years, inclusive
  • Female subjects ages 15 to 17 years, inclusive
  • Male subjects ages 12 to 14 years, inclusive
  • Male subjects ages 15 to 17 years, inclusive

Phase (A) of this study will last 12 months. After that time, all subjects who qualify will be assigned tolvaptan and will be treated with tolvaptan for 24 months (Phase B).

A qualified subject is defined as one who has completed Phase A on investigational medicinal product (IMP), is willing to continue in the trial, and who does not have any adverse events (AEs), which would require IMP discontinuation.

Participants in this study will be required to make monthly visits to the study clinic and will be closely monitored over the course of the study.

  Eligibility

Ages Eligible for Study:   4 Years to 17 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Male and female subjects aged 4 to 17 years (inclusive) with a diagnosis of ADPKD as defined by the presence of family history and/or genetic criteria AND who have at least 10 renal cysts, each of which measure at least 0.5 cm, confirmed upon magnetic resonance imaging (MRI) inspection; subjects under the age of 12 years must have at least 4 cysts that are at least 1 cm in size, confirmed by ultrasound.
  • Weight ≥ 20 kg.
  • Subjects with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2 within 31 days prior to randomization (using the Schwartz formula, eGFR = 0.413 × height [cm]/serum creatinine mg/dL).
  • Independent in toileting.
  • Ability to swallow a tablet.

Key Exclusion Criteria:

  • Liver function tests including AST (aspartate aminotransferase), ALT (alanine aminotransferase) > 1.5 × the upper limit of normal (ULN).
  • Nocturnal enuresis.
  • Need for chronic diuretic use.
  • Subjects with advanced diabetes (eg, glycosylated hemoglobin > 7.5, and/or glycosuria by dipstick, significant proteinuria, retinopathy), evidence of additional significant renal disease(s) (ie, currently active glomerular nephritides), renal cancer, single kidney, or recent (within 6 months of screening) renal surgery or acute kidney injury.
  • Subjects having disorders in thirst recognition or inability to access fluids.
  • Subjects with critical electrolyte imbalances, as determined by the investigator.
  • Subjects with, or at risk of, significant hypovolemia as determined by investigator.
  • Subjects with clinically significant anemia, as determined by investigator.
  • Subjects 12 years of age and older having contraindications to, or interference with MRI assessments (eg, ferro-magnetic prostheses, aneurysm clips, severe claustrophobia).
  • Subjects with a history of taking a vasopressin agonist/antagonist.
  • Subjects taking medications or having concomitant illnesses likely to confound endpoint assessments, including taking approved (ie, marketed) therapies for the purpose of affecting polycystic kidney disease (PKD) cysts such as tolvaptan, vasopressin antagonists, anti-sense ribonucleic acid (RNA) therapies, rapamycin, sirolimus, everolimus, or somatostatin analogs (ie, octreotide, sandostatin).
  • Subjects who have had cyst reduction surgery within 6 weeks of the screening visit.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02964273

Contacts
Contact: Taylor Cook 919-397-5305 Taylor.Cook@INCResearch.com
Contact: Sarah van Leeuwen +310203018569 Sarah.vanLeeuwen@INCResearch.com

Locations
Belgium
Recruiting
Gent, Oost-Vlaanderen, Belgium, 9000
Recruiting
Leuven, Vlaams Brabant, Belgium, 3000
Italy
Recruiting
Pavia, Italy, 27100
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
Study Director: Ann Dandurand, MD Otsuka Pharmaceutical Development & Commercialization, Inc.
  More Information

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT02964273     History of Changes
Other Study ID Numbers: 156-12-298 
Study First Received: September 15, 2016
Last Updated: November 10, 2016
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Autosomal Dominant Polycystic Kidney Disease
ADPKD
Tolvaptan
Renal cysts
Chronic Kidney Disease
Genetic Kidney Disease

Additional relevant MeSH terms:
Kidney Diseases
Polycystic Kidney Diseases
Polycystic Kidney, Autosomal Dominant
Urologic Diseases
Kidney Diseases, Cystic
Tolvaptan
Antidiuretic Hormone Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 02, 2016