Trial Outcomes & Findings for Effectiveness of Paricalcitol in Reducing Parathyroid Hormone (PTH) Levels in X-linked Hypophosphatemic Rickets (NCT NCT00417612)
NCT ID: NCT00417612
Last Updated: 2020-03-17
Results Overview
Mean area under the curve for parathyroid hormone levels (PTHauc) sampled during a 26 hour study period, for Paricalcitol (Active Drug) and Placebo groups at Baseline and Month 12 .
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
33 participants
Primary outcome timeframe
Measured at baseline and Month 12
Results posted on
2020-03-17
Participant Flow
Participant milestones
| Measure |
Paricalcitol (Active Drug)
Participants given active drug, paricalcitol (Zemplar), in effort to reduce Parathyroid Hormone (PTH) level
Paricalcitol: Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits.
|
Placebo
Participants given placebo capsule to match for comparison
Placebo: Placebo sugar pill
|
|---|---|---|
|
Overall Study
STARTED
|
22
|
11
|
|
Overall Study
COMPLETED
|
19
|
8
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
Reasons for withdrawal
| Measure |
Paricalcitol (Active Drug)
Participants given active drug, paricalcitol (Zemplar), in effort to reduce Parathyroid Hormone (PTH) level
Paricalcitol: Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits.
|
Placebo
Participants given placebo capsule to match for comparison
Placebo: Placebo sugar pill
|
|---|---|---|
|
Overall Study
Errant diagnosis
|
0
|
1
|
|
Overall Study
Adverse Event
|
2
|
0
|
|
Overall Study
Protocol Violation
|
0
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
Baseline Characteristics
Effectiveness of Paricalcitol in Reducing Parathyroid Hormone (PTH) Levels in X-linked Hypophosphatemic Rickets
Baseline characteristics by cohort
| Measure |
Paricalcitol (Active Drug)
n=22 Participants
Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level
Paricalcitol: Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits.
|
Placebo
n=11 Participants
Participants given placebo capsule to match for comparison
Placebo: Placebo sugar pill
|
Total
n=33 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
2 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
19 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
29 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
26 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
22 participants
n=93 Participants
|
11 participants
n=4 Participants
|
33 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Measured at baseline and Month 12Mean area under the curve for parathyroid hormone levels (PTHauc) sampled during a 26 hour study period, for Paricalcitol (Active Drug) and Placebo groups at Baseline and Month 12 .
Outcome measures
| Measure |
Paricalcitol (Active Drug)
n=19 Participants
Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level
Paricalcitol: Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits.
|
Placebo
n=8 Participants
Participants given placebo capsule to match for comparison
Placebo: Placebo sugar pill
|
Paricalcitol (Children Ages 9-17)
Pediatric patients ages 9-17 given paricalcitol
|
|---|---|---|---|
|
Area Under the Curve for Parathyroid Hormone (PTHauc) Measurement
Baseline
|
1223 nlEq*26hr/ml
Standard Deviation 426
|
1449 nlEq*26hr/ml
Standard Deviation 865
|
—
|
|
Area Under the Curve for Parathyroid Hormone (PTHauc) Measurement
Month 12
|
987 nlEq*26hr/ml
Standard Deviation 372
|
1616 nlEq*26hr/ml
Standard Deviation 945
|
—
|
PRIMARY outcome
Timeframe: Measured at baseline and Month 12Mean PTHauc (% decrease) for Paricalcitol (Active Drug) and Placebo from Baseline to Month 12.
Outcome measures
| Measure |
Paricalcitol (Active Drug)
n=19 Participants
Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level
Paricalcitol: Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits.
|
Placebo
n=8 Participants
Participants given placebo capsule to match for comparison
Placebo: Placebo sugar pill
|
Paricalcitol (Children Ages 9-17)
Pediatric patients ages 9-17 given paricalcitol
|
|---|---|---|---|
|
Area Under the Curve for Parathyroid Hormone (PTH; Percentage Decrease)
20-29%
|
5 participants
|
1 participants
|
—
|
|
Area Under the Curve for Parathyroid Hormone (PTH; Percentage Decrease)
30-39%
|
1 participants
|
1 participants
|
—
|
|
Area Under the Curve for Parathyroid Hormone (PTH; Percentage Decrease)
>/= 40%
|
3 participants
|
0 participants
|
—
|
PRIMARY outcome
Timeframe: Measured at baseline and Month 12Clinically significant reduction of Mean PTHauc (% decrease \>/= 20) for Paricalcitol (Active Drug) and Placebo from Baseline to Month 12.
Outcome measures
| Measure |
Paricalcitol (Active Drug)
n=19 Participants
Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level
Paricalcitol: Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits.
|
Placebo
n=8 Participants
Participants given placebo capsule to match for comparison
Placebo: Placebo sugar pill
|
Paricalcitol (Children Ages 9-17)
Pediatric patients ages 9-17 given paricalcitol
|
|---|---|---|---|
|
Reduction of Parathyroid Hormone Area Under the Curve (PTHauc) of 20% or Greater
|
53 percentage of participants
|
25 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Measured at baseline and Month 12Population: Alkaline phosphatase activity was analyzed separately for children (less than 18 years of age) and adults as values varied considerably between these two groups. In other outcome measure modules the paricalcitol group is comprised of 19 participants analyzed which includes adults and children. In this module, the children (2) are their own arm.
Outcome measures
| Measure |
Paricalcitol (Active Drug)
n=17 Participants
Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level
Paricalcitol: Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits.
|
Placebo
n=8 Participants
Participants given placebo capsule to match for comparison
Placebo: Placebo sugar pill
|
Paricalcitol (Children Ages 9-17)
n=2 Participants
Pediatric patients ages 9-17 given paricalcitol
|
|---|---|---|---|
|
Static Parameters of Serum Alkaline Phosphatase at Baseline and 1 Year for Paricalcitol and Placebo Arms.
Serum Alkaline Phosphatase (1 Year)
|
112 mg/dl
Standard Deviation 70
|
98 mg/dl
Standard Deviation 34
|
402 mg/dl
Standard Deviation 211
|
|
Static Parameters of Serum Alkaline Phosphatase at Baseline and 1 Year for Paricalcitol and Placebo Arms.
Serum Alkaline Phosphatase (Baseline)
|
141 mg/dl
Standard Deviation 96
|
96 mg/dl
Standard Deviation 28
|
354 mg/dl
Standard Deviation 2
|
SECONDARY outcome
Timeframe: Measured at baseline and Month 12Outcome measures
| Measure |
Paricalcitol (Active Drug)
n=19 Participants
Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level
Paricalcitol: Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits.
|
Placebo
n=8 Participants
Participants given placebo capsule to match for comparison
Placebo: Placebo sugar pill
|
Paricalcitol (Children Ages 9-17)
Pediatric patients ages 9-17 given paricalcitol
|
|---|---|---|---|
|
Serum Calcium
Serum Calcium (Baseline)
|
9.2 mg/dl
Standard Deviation 0.5
|
9.3 mg/dl
Standard Deviation 0.5
|
—
|
|
Serum Calcium
Serum Calcium (1 Year)
|
9.4 mg/dl
Standard Deviation 0.5
|
9.3 mg/dl
Standard Deviation 0.5
|
—
|
SECONDARY outcome
Timeframe: Measured at baseline and Month 1299-Tc-methylenediphosphonate bone scans were completed and analyzed using the following scale\*: Bone scan severity scale with minimum score of 0 and maximum score of 4 (0 is no disease and 4 is greatest severity of disease). Appearance of lumbar spine and the sacroiliac region were used as internal references to which all suspected lesions were compared, and scored as follows: grade 0, normal scan without suspicious lesions grade 1, lesion(s) less intense than normal lumbar spine grade 2, lesion(s) similar in intensity to normal lumbar spine grade 3, lesions more intense than normal lumbar spine but similar to the normal sacroiliac region grade 4, lesions more intense than the normal sacroiliac region. \*devised by nuclear medicine radiologist at Yale New Haven Hospital
Outcome measures
| Measure |
Paricalcitol (Active Drug)
n=19 Participants
Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level
Paricalcitol: Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits.
|
Placebo
n=8 Participants
Participants given placebo capsule to match for comparison
Placebo: Placebo sugar pill
|
Paricalcitol (Children Ages 9-17)
Pediatric patients ages 9-17 given paricalcitol
|
|---|---|---|---|
|
Bone Scan Severity Score
12 Month Scan Score
|
1.76 units on a scale
Standard Deviation 1.25
|
2.12 units on a scale
Standard Deviation 1.55
|
—
|
|
Bone Scan Severity Score
Baseline Scan Score
|
2.18 units on a scale
Standard Deviation 1.19
|
2.00 units on a scale
Standard Deviation 1.51
|
—
|
SECONDARY outcome
Timeframe: Measured at baseline and Month 12Percent change in daily urinary calcium excretion, which is calculated the measurements of the calcium in the subject's 24-hr urine collections done at baseline and at the 1 year timepoints
Outcome measures
| Measure |
Paricalcitol (Active Drug)
n=19 Participants
Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level
Paricalcitol: Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits.
|
Placebo
n=8 Participants
Participants given placebo capsule to match for comparison
Placebo: Placebo sugar pill
|
Paricalcitol (Children Ages 9-17)
Pediatric patients ages 9-17 given paricalcitol
|
|---|---|---|---|
|
Percent Change in Urinary Calcium Excretion From Baseline to 1 Year
|
253 percent change
Standard Deviation 388
|
9 percent change
Standard Deviation 36
|
—
|
SECONDARY outcome
Timeframe: Measured at baseline and Month 12Outcome measures
| Measure |
Paricalcitol (Active Drug)
n=19 Participants
Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level
Paricalcitol: Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits.
|
Placebo
n=8 Participants
Participants given placebo capsule to match for comparison
Placebo: Placebo sugar pill
|
Paricalcitol (Children Ages 9-17)
Pediatric patients ages 9-17 given paricalcitol
|
|---|---|---|---|
|
Serum Intact Fibroblast Growth Factor 23 (FGF23)
Serum Intact FGF23 (Baseline)
|
120 pg/ml
Interval 72.0 to 203.0
|
93 pg/ml
Interval 46.0 to 188.0
|
—
|
|
Serum Intact Fibroblast Growth Factor 23 (FGF23)
Serum Intact FGF23 (1 Year)
|
244 pg/ml
Interval 145.0 to 411.0
|
104 pg/ml
Interval 47.0 to 227.0
|
—
|
SECONDARY outcome
Timeframe: Measured at baseline and Month 12Outcome measures
| Measure |
Paricalcitol (Active Drug)
n=19 Participants
Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level
Paricalcitol: Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits.
|
Placebo
n=8 Participants
Participants given placebo capsule to match for comparison
Placebo: Placebo sugar pill
|
Paricalcitol (Children Ages 9-17)
Pediatric patients ages 9-17 given paricalcitol
|
|---|---|---|---|
|
Serum 1,25 (OH)2D
Serum 1,25(OH)2D (Baseline)
|
51 pg/ml
Standard Deviation 18
|
47 pg/ml
Standard Deviation 9
|
—
|
|
Serum 1,25 (OH)2D
Serum 1,25 (OH)2D (1 Year)
|
52 pg/ml
Standard Deviation 17
|
46 pg/ml
Standard Deviation 14
|
—
|
Adverse Events
Paricalcitol (Active Drug)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Paricalcitol (Active Drug)
n=22 participants at risk
Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level
Paricalcitol: Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits.
|
Placebo
n=11 participants at risk
Participants given placebo capsule to match for comparison
Placebo: Placebo sugar pill
|
|---|---|---|
|
Renal and urinary disorders
Elevated Serum Creatinine
|
4.5%
1/22 • Number of events 1
|
0.00%
0/11
|
|
Blood and lymphatic system disorders
Hypercalcemia
|
4.5%
1/22 • Number of events 1
|
0.00%
0/11
|
Additional Information
Dr. Thomas O. Carpenter
Yale University School of Medicine
Phone: 203-785-6526
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place