Chronic Kidney Disease Stage 3 and 4Phase 3NCT01020487
Safety and Efficacy of Paricalcitol Capsules in Decreasing Serum Parathyroid Hormone Levels in Children Aged 10-16 With Chronic Kidney Disease (CKD)
A Phase 3 study testing Paricalcitol in people with Chronic Kidney Disease Stage 3 and 4, run by AbbVie (prior sponsor, Abbott).
Trial summary
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). Read more about this study
- Who is it for?
- Ages 10 to 16 years
- Conditions the study is for
- Chronic Kidney Disease Stage 3 and 4
- What is being tested?
- Paricalcitol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 47 participants
- Where
- No sites listed yet
- Study dates
- Feb 2010to Dec 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Chronic Kidney Disease Stage 3 and 4
- Being tested
- Paricalcitol, Placebo
- Keywords
- Reduction of parathyroid hormone levels in pediatric patients with Chronic Kidney Disease Stage 3 and 4
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ParicalcitolDrug
Also called Zemplar
Paricalcitol capsules taken with water.
PlaceboDrug
Placebo capsules taken with water
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Paricalcitol | Experimental | Participants received a single 3 µg dose of paricalcitol capsules on Study Day 1. Receives: Drug: Paricalcitol |
| Part 2: Placebo | Placebo comparator | 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. Receives: Drug: Paricalcitol; Drug: Placebo |
| Part 2: Paricalcitol | Experimental | 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. Receives: Drug: Paricalcitol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Paricalcitol Maximum Observed Plasma Concentration (Cmax)
Measured: Blood samples were collected at hour 0, 1, 2, 4, 6, 8, 12, 24, 36, and 48 hours after dosing.
Part 1: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞)
Measured: Blood samples were collected at hour 0, 1, 2, 4, 6, 8, 12, 24, 36, and 48 hours after dosing.
Part 2: Percentage of Participants Achieving Two Consecutive Reductions at Least 30% From Baseline in iPTH
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.
Measured: 12-week double-blind treatment period
Secondary outcomes (5)
Part 2: Percentage of Participants Achieving a Final iPTH Within KDOQI Target Ranges
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.
Measured: Week 12
Part 2: Change From Baseline in iPTH to Each Post-baseline Visit
Measured: Baseline and Weeks 2, 4, 8 and 12
Part 2: Percentage of Participants Achieving Final Calcium Levels Within KDOQI Target Ranges
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).
Measured: Week 12
Part 2: Percentage of Participants Achieving Final Phosphorus Levels Within KDOQI Target Ranges
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).
Measured: Week 12
Part 2: Change From Baseline in First Morning Void (FMV) Urinary Albumin to Creatinine Ratio (UACR)
The mean change from Baseline in FMV UACR on a log scale to each post baseline visit.
Measured: Baseline and Weeks 4, 8 and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2009 (estimated)
- Study startFeb 2010
- Primary completionMay 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Kidney Disease Stage 3 and 4Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie (prior sponsor, Abbott)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Deepa Chand, MD, Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01020487
- Sponsor's protocol ID
- M10-149
- Other IDs
- 2010-019439-37
- Status last verified
- Feb 2017
- First submitted
- 13 Nov 2009
- Last updated
- 2 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Webb NJA, Lerner G, Warady BA, Dell KM, Greenbaum LA, Ariceta G, Hoppe B, Linde P, Lee HJ, Eldred A, Dufek MB. Efficacy and safety of paricalcitol in children with stages 3 to 5 chronic kidney disease. Pediatr Nephrol. 2017 Jul;32(7):1221-1232. doi: 10.1007/s00467-017-3579-6. Epub 2017 Mar 22.
PubMed 28332096
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01020487
- Acronym / sponsor ID
- M10-149
- Conditions
- Chronic Kidney Disease Stage 3 and 4
- Keywords
- Reduction of parathyroid hormone levels in pediatric patients with Chronic Kidney Disease Stage 3 and 4
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- AbbVie (prior sponsor, Abbott)Industry (pharma, biotech, devices)
- Study start
- Feb 2010
- Primary completion
- May 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 24 Nov 2009 (estimated)
- Results
- Posted 29 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1: Paricalcitol | Experimental | Drug: ParicalcitolParticipants received a single 3 µg dose of paricalcitol capsules on Study Day 1. |
| Part 2: Placebo | Placebo comparator | Drug: Paricalcitol, Drug: PlaceboParticipants 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. |
| Part 2: Paricalcitol | Experimental | Drug: ParicalcitolParticipants 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. |
Who may qualify
- Ages
- 10 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (12 listed)
- 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:
- 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:
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ParicalcitolAlso: ZemplarParicalcitol capsules taken with water. | Drug | Part 1: Paricalcitol, Part 2: Paricalcitol, Part 2: Placebo |
| PlaceboPlacebo capsules taken with water | Drug | Part 2: Placebo |
Primary outcome
Part 1: Paricalcitol Maximum Observed Plasma Concentration (Cmax)
Time frame: Blood samples were collected at hour 0, 1, 2, 4, 6, 8, 12, 24, 36, and 48 hours after dosing.
Part 1: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞)
Time frame: Blood samples were collected at hour 0, 1, 2, 4, 6, 8, 12, 24, 36, and 48 hours after dosing.
Part 2: Percentage of Participants Achieving Two Consecutive Reductions at Least 30% From Baseline in iPTH
Time frame: 12-week double-blind treatment period
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.
5 secondary outcomes
Part 2: Percentage of Participants Achieving a Final iPTH Within KDOQI Target Ranges
Time frame: Week 12
Part 2: Change From Baseline in iPTH to Each Post-baseline Visit
Time frame: Baseline and Weeks 2, 4, 8 and 12
Part 2: Percentage of Participants Achieving Final Calcium Levels Within KDOQI Target Ranges
Time frame: Week 12
Part 2: Percentage of Participants Achieving Final Phosphorus Levels Within KDOQI Target Ranges
Time frame: Week 12
Part 2: Change From Baseline in First Morning Void (FMV) Urinary Albumin to Creatinine Ratio (UACR)
Time frame: Baseline and Weeks 4, 8 and 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28332096Webb NJA, Lerner G, Warady BA, Dell KM, Greenbaum LA, Ariceta G, Hoppe B, Linde P, Lee HJ, Eldred A, Dufek MB. Efficacy and safety of paricalcitol in children with stages 3 to 5 chronic kidney disease. Pediatr Nephrol. 2017 Jul;32(7):1221-1232. doi: 10.1007/s00467-017-3579-6. Epub 2017 Mar 22.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Deepa Chand, MD study director
AbbVie
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Paricalcitol in people with Chronic Kidney Disease Stage 3 and 4, run by AbbVie (prior sponsor, Abbott).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Paricalcitol Maximum Observed Plasma Concentration (Cmax) (time frame: Blood samples were collected at hour 0, 1, 2, 4, 6, 8, 12, 24, 36, and 48 hours after dosing.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01020487, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2018.