Secondary Hyperparathyroidism-Chronic Kidney Disease
Conditions
Brief summary
Primary Objective: Evaluated the effect of Hectorol® capsules in reducing elevated levels of intact parathyroid hormone (iPTH). Secondary Objectives: * Evaluated the safety profile of Hectorol® capsules versus Rocaltrol® (calcitriol) capsules. * Determined the pharmacokinetic profile of 1,25-dihydroxyvitamin D2 after administration of Hectorol®.
Detailed description
The total study duration per participant was approximately up to 28 weeks.
Interventions
DRUGDoxercalciferol (GZ427397)
Pharmaceutical form: capsule Route of administration: oral
DRUGCalcitriol
Pharmaceutical form: capsule Route of administration: oral
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
: * Male or female aged 5 to 18 years old. * Weight ≥15 kg. * Chronic kidney disease (CKD) Stage 3 or 4 not on dialysis, defined as glomerular filtration rate (GFR) between 15 and 59 mL/min/1.73m\^2 (established by Schwartz equation) at Week -2 visit. * Intact parathyroid hormone (iPTH) value \>100 pg/mL for CKD Stage 3 or \>160 pg/mL for CKD Stage 4, at Week -2 visit. * Signed informed consent/assent form.
Exclusion criteria
* The participant had a serum 25-hydroxyvitamin D level \<30 ng/mL at screening. * The participant had a corrected calcium ≥10 mg/dL at the Week -2 visit. * The participant had a serum phosphorus \>4.5 mg/dL for children 13 to 18 years of age; \>5.8 mg/dL for children 5 to 12 years of age at the Week -2 visit. * The participant was anticipated to require maintenance hemodialysis within 3 months. * The participant used cinacalcet or vitamin D sterol therapies such as calcitriol, doxercalciferol, or paricalcitol within 14 days prior to the baseline visit. * The participant had a history of, or active, symptomatic heart disease within 12 months prior to the baseline (Week 0) visit. * The participant had a chronic gastrointestinal disease (ie, malabsorption, severe chronic diarrhea, chronic ulcerative colitis, or ileostomy). * The participant had primary hyperparathyroidism or has had a total parathyroidectomy. * The participant had an active malignancy. * The participant was unable to swallow a capsule in size similar to the Hectorol® and Rocaltrol® capsules. * The participant had a history of sensitivity or allergy to doxercalciferol, calcitriol or other vitamin D analogs. * The participant used aluminum or magnesium-based binders. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved 2 Consecutive >=30% Reductions in Intact Parathyroid Hormone From Baseline up to Week 12 | Baseline (Day 1) up to Week 12 | Blood samples were collected for assessment of iPTH levels. The percentage of participants meeting the iPTH \>=30% reduction from baseline at 2 consecutive study visits up to Week 12 was calculated. Two consecutive \>=30% reductions in iPTH from baseline up to Week 12 was defined as two consecutive 30% or greater reductions at any two consecutive measurements from baseline up to Week 12 with on-treatment strategy applied. The confidence interval (CI) was estimated using Clopper-Pearson method. The baseline value is defined as the last available value before the first dose of study treatment. Percentages are rounded off to the tenth decimal place. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Intact Parathyroid Hormone From Baseline to Weeks 12 and 24 | Baseline (Day 1) to Weeks 12 and 24 | Blood samples were collected for assessment of iPTH levels. The percentage changes from baseline iPTH, the effects over the treatment period time was explored using a mixed model for repeated measures approach (MMRM) as appropriate. The baseline value is defined as the last available value before the first dose of study treatment. |
| Number of Hypercalcemia Events up to Weeks 12 and 24 | Up to Weeks 12 and 24 | Hypercalcemia was defined as albumin corrected serum calcium \>10.2 milligrams per deciliter (mg/dL). Here, data for number of hypercalcemia events are reported. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | From first dose of study treatment (Day 1) up to 4 days after the last dose of study treatment; approximately 36 weeks | An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant who was administered a pharmaceutical product, and which did not necessarily have a causal relationship with this treatment. An AE occurred or was detected from the date the participant signed the informed consent form, irrespective of study periods without administration of the study treatment. TEAEs were defined as the AEs that developed, worsened or became serious during the treatment-emergent period (defined as time from administration of study treatment \[Day 1\] to last administration of study treatment + 4 days). SAE: Any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. |
| Maximum Observed Plasma Concentration (Cmax) of 1,25-Dihydroxyvitamin D2 at Week 8 or 10 | Pre-dose, 1, 4, 7, and 24 hours post-dose at Week 8 or 10 | Blood samples were collected at specified timepoints after administration of doxercalciferol (Hectorol®) to determine Cmax. Evaluation of the 1, 25-Dihydroxyvitamin D2 concentration-time data was obtained using non-compartmental methods. As pre-specified in protocol pharmacokinetic (PK) parameters were assessed at Week 8 or Week 10 choice was as per the schedule availability of the site and the participants. |
| Time to Maximum Plasma Concentration (Tmax) of 1,25-Dihydroxyvitamin D2 at Week 8 or 10 | Pre-dose, 1, 4, 7, and 24 hours post-dose at Week 8 or 10 | Blood samples were collected at specified timepoints after administration of doxercalciferol (Hectorol®) to determine tmax. Evaluation of the 1, 25-Dihydroxyvitamin D2 concentration-time data was obtained using non-compartmental methods. As pre-specified in protocol PK parameters were assessed at Week 8 or Week 10 choice was as per the schedule availability of the site and the participants. |
| Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24h) of 1,25-Dihydroxyvitamin D2 at Week 8 or 10 | Pre-dose, 1, 4, 7, and 24 hours post-dose at Week 8 or 10 | Blood samples were collected at specified timepoints after administration of doxercalciferol (Hectorol®) to determine AUC0-24h. Evaluation of the 1, 25-Dihydroxyvitamin D2 concentration-time data was obtained using non-compartmental methods. As pre-specified in protocol PK parameters were assessed at Week 8 or Week 10 choice was as per the schedule availability of the site and the participants. |
| Trough Plasma Concentration (Ctrough) of 1,25-Dihydroxyvitamin D2 at Week 8 or 10 | Pre-dose, 1, 4, 7, and 24 hours post-dose at Week 8 or 10 | Blood samples were collected at specified timepoints after administration of doxercalciferol (Hectorol®) to determine Ctrough. Evaluation of the 1, 25-Dihydroxyvitamin D2 concentration-time data was obtained using non-compartmental methods. As pre-specified in protocol PK parameters were assessed at Week 8 or Week 10 choice was as per the schedule availability of the site and the participants. |
Countries
Chile, United States
Contacts
STUDY_DIRECTORClinical Sciences & Operations
Sanofi
Participant flow
Recruitment details
The study was conducted at 23 centers in 2 countries. A total of 59 participants were screened from 19 January 2017 to 05 February 2020, of which 38 were screen failures. Screen failures were mainly due to participants did not meet the inclusion/exclusion criteria of the study.
Pre-assignment details
A total of 21 participants were randomized in a 2:1 ratio to receive either doxercalciferol (Hectorol®) or calcitriol (Rocaltrol®). The study was conducted to fulfill a post-marketing commitment (PMC). The study was terminated as food and drug administration (FDA) acknowledged the fulfillment of this PMC on 11 June 2025. Note: Reason for not completed = Reason for permanent treatment discontinuation.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 11.4 years STANDARD_DEVIATION 4.2 |
| Race/Ethnicity, Customized Black or African American | 2 Participants |
| Race/Ethnicity, Customized Not reported | 2 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants |
| Race/Ethnicity, Customized White | 15 Participants |
| Race/Ethnicity, Customized White/Black or African American | 1 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 7 |
| other Total, other adverse events | 11 / 14 | 6 / 7 |
| serious Total, serious adverse events | 3 / 14 | 0 / 7 |
Outcome results
None listed