Trial Outcomes & Findings for Comparison of Efficacy and Safety of Paricalcitol Injection With Maxacalcitol Injection in Adult Japanese Chronic Kidney Disease Subjects Receiving Hemodialysis With Secondary Hyperparathyroidism (NCT NCT01341782)
NCT ID: NCT01341782
Last Updated: 2013-06-06
Results Overview
The target iPTH range was 60-180 pg/mL, based on the average of the last 3 weeks of treatment, and with no hypercalcemia during the treatment phase. Hypercalcemia was defined as at least 1 corrected calcium value \> 11.0 mg/dL or at least 2 corrected calcium values ≥ 10.5 mg/dL. iPTH was measured before the first dialysis session of each week and analyzed by the central laboratory.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
255 participants
Primary outcome timeframe
iPTH measured during the last three weeks of treatment (Weeks 11, 12, and 13). Calcium measured throughout the study (Weeks 1-13).
Results posted on
2013-06-06
Participant Flow
Participant milestones
| Measure |
Paricalcitol
Participants received paricalcitol at an initial dose of 2 µg, and maxacalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 1 µg based on protocol-specified criteria up to a maximum of 7 µg.
|
Maxacalcitol
Participants received maxacalcitol at an initial dose of 5 µg (intact parathyroid hormone \[iPTH\] \< 500 pg/mL at Screening) or 10 µg (iPTH ≥ 500 pg/mL at Screening), and paricalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 2.5 µg based on protocol-specified criteria up to a maximum of 20 µg.
|
|---|---|---|
|
Overall Study
STARTED
|
127
|
128
|
|
Overall Study
COMPLETED
|
112
|
114
|
|
Overall Study
NOT COMPLETED
|
15
|
14
|
Reasons for withdrawal
| Measure |
Paricalcitol
Participants received paricalcitol at an initial dose of 2 µg, and maxacalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 1 µg based on protocol-specified criteria up to a maximum of 7 µg.
|
Maxacalcitol
Participants received maxacalcitol at an initial dose of 5 µg (intact parathyroid hormone \[iPTH\] \< 500 pg/mL at Screening) or 10 µg (iPTH ≥ 500 pg/mL at Screening), and paricalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 2.5 µg based on protocol-specified criteria up to a maximum of 20 µg.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
6
|
5
|
|
Overall Study
Missed 3 consecutive doses
|
0
|
4
|
|
Overall Study
2 consecutive calcium values >11.5 mg/dL
|
0
|
1
|
|
Overall Study
2 consecutive calcium values < 8.4 mg/dL
|
3
|
3
|
|
Overall Study
Other
|
5
|
0
|
Baseline Characteristics
Comparison of Efficacy and Safety of Paricalcitol Injection With Maxacalcitol Injection in Adult Japanese Chronic Kidney Disease Subjects Receiving Hemodialysis With Secondary Hyperparathyroidism
Baseline characteristics by cohort
| Measure |
Paricalcitol
n=127 Participants
Participants received paricalcitol at an initial dose of 2 µg, and maxacalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 1 µg based on protocol-specified criteria up to a maximum of 7 µg.
|
Maxacalcitol
n=128 Participants
Participants received maxacalcitol at an initial dose of 5 µg (iPTH \< 500 pg/mL at Screening) or 10 µg (iPTH ≥ 500 pg/mL at Screening), and paricalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 2.5 µg based on protocol-specified criteria up to a maximum of 20 µg.
|
Total
n=255 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
61.5 years
STANDARD_DEVIATION 11.24 • n=5 Participants
|
61.6 years
STANDARD_DEVIATION 12.46 • n=7 Participants
|
61.6 years
STANDARD_DEVIATION 11.85 • n=5 Participants
|
|
Sex: Female, Male
Female
|
45 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
92 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
82 Participants
n=5 Participants
|
81 Participants
n=7 Participants
|
163 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
127 participants
n=5 Participants
|
128 participants
n=7 Participants
|
255 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
127 participants
n=5 Participants
|
128 participants
n=7 Participants
|
255 participants
n=5 Participants
|
|
Duration of hemodialysis
|
8.4 years
STANDARD_DEVIATION 6.73 • n=5 Participants
|
8.9 years
STANDARD_DEVIATION 7.50 • n=7 Participants
|
8.6 years
STANDARD_DEVIATION 7.12 • n=5 Participants
|
|
Intact parathyroid hormone level
|
525.4 pg/mL
STANDARD_DEVIATION 205.55 • n=5 Participants
|
527.1 pg/mL
STANDARD_DEVIATION 203.33 • n=7 Participants
|
526.3 pg/mL
STANDARD_DEVIATION 204.03 • n=5 Participants
|
PRIMARY outcome
Timeframe: iPTH measured during the last three weeks of treatment (Weeks 11, 12, and 13). Calcium measured throughout the study (Weeks 1-13).Population: The per-protocol set (PPS) consists of all randomized patients who completed at least 8 weeks of treatment and met the conditions specified by the subject classification (i.e., no violation of inclusion/exclusion criteria) that occurred before the study blind was broken.
The target iPTH range was 60-180 pg/mL, based on the average of the last 3 weeks of treatment, and with no hypercalcemia during the treatment phase. Hypercalcemia was defined as at least 1 corrected calcium value \> 11.0 mg/dL or at least 2 corrected calcium values ≥ 10.5 mg/dL. iPTH was measured before the first dialysis session of each week and analyzed by the central laboratory.
Outcome measures
| Measure |
Paricalcitol
n=119 Participants
Participants received paricalcitol at an initial dose of 2 µg, and maxacalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 1 µg based on protocol-specified criteria up to a maximum of 7 µg.
|
Maxacalcitol
n=118 Participants
Participants received maxacalcitol at an initial dose of 5 µg (iPTH \< 500 pg/mL at Screening) or 10 µg (iPTH ≥ 500 pg/mL at Screening), and paricalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 2.5 µg based on protocol-specified criteria up to a maximum of 20 µg.
|
|---|---|---|
|
Percentage of Participants With Target Intact Parathyroid Hormone (iPTH) and Without Hypercalcemia
|
27.7 percentage of participants
Interval 19.92 to 36.68
|
30.5 percentage of participants
Interval 22.37 to 39.66
|
SECONDARY outcome
Timeframe: Baseline to the last three weeks of treatment (Weeks 11, 12, and 13) for iPTH. Calcium measured throughout the study (Weeks 1-13).Population: The Full Analysis Set (FAS) consists of all randomized patients who received at least 1 dose of study drug and had at least 1 post-baseline iPTH measurement.
The percentage of participants with greater than or equal to 50% reduction in intact parathyroid hormone (iPTH) from baseline to the average of the last 3 weeks of treatment and with no hypercalcemia during the treatment phase. iPTH was measured before the first dialysis session of each week and analyzed by the central laboratory. Hypercalcemia was defined as at least 1 corrected calcium value \> 11.0 mg/dL or at least 2 corrected calcium values ≥ 10.5 mg/dL.
Outcome measures
| Measure |
Paricalcitol
n=127 Participants
Participants received paricalcitol at an initial dose of 2 µg, and maxacalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 1 µg based on protocol-specified criteria up to a maximum of 7 µg.
|
Maxacalcitol
n=128 Participants
Participants received maxacalcitol at an initial dose of 5 µg (iPTH \< 500 pg/mL at Screening) or 10 µg (iPTH ≥ 500 pg/mL at Screening), and paricalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 2.5 µg based on protocol-specified criteria up to a maximum of 20 µg.
|
|---|---|---|
|
Percentage of Participants With ≥ 50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline and With No Hypercalcemia
|
34.6 percentage of participants
Interval 26.43 to 43.6
|
39.1 percentage of participants
Interval 30.56 to 48.08
|
SECONDARY outcome
Timeframe: The last three weeks of treatment (Weeks 11, 12, and 13)Population: Full analysis set
The target iPTH range was 60-180 pg/mL, based on the average of the last 3 weeks of treatment. iPTH was measured before the first dialysis session of each week and analyzed by the central laboratory.
Outcome measures
| Measure |
Paricalcitol
n=127 Participants
Participants received paricalcitol at an initial dose of 2 µg, and maxacalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 1 µg based on protocol-specified criteria up to a maximum of 7 µg.
|
Maxacalcitol
n=128 Participants
Participants received maxacalcitol at an initial dose of 5 µg (iPTH \< 500 pg/mL at Screening) or 10 µg (iPTH ≥ 500 pg/mL at Screening), and paricalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 2.5 µg based on protocol-specified criteria up to a maximum of 20 µg.
|
|---|---|---|
|
Percentage of Participants With Target Intact Parathyroid Hormone (iPTH)
|
31.5 percentage of participants
Interval 23.55 to 40.33
|
32.8 percentage of participants
Interval 24.78 to 41.67
|
SECONDARY outcome
Timeframe: Baseline to the last three weeks of treatment (Weeks 11, 12, and 13)Population: Full analysis set
The percentage of participants with a greater than or equal to 50% reduction in intact parathyroid hormone (iPTH) from baseline to the average of the last 3 weeks of treatment. iPTH was measured before the first dialysis session of each week and analyzed by the central laboratory.
Outcome measures
| Measure |
Paricalcitol
n=127 Participants
Participants received paricalcitol at an initial dose of 2 µg, and maxacalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 1 µg based on protocol-specified criteria up to a maximum of 7 µg.
|
Maxacalcitol
n=128 Participants
Participants received maxacalcitol at an initial dose of 5 µg (iPTH \< 500 pg/mL at Screening) or 10 µg (iPTH ≥ 500 pg/mL at Screening), and paricalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 2.5 µg based on protocol-specified criteria up to a maximum of 20 µg.
|
|---|---|---|
|
Percentage of Participants With ≥ 50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline
|
44.9 percentage of participants
Interval 36.05 to 53.96
|
50.8 percentage of participants
Interval 41.8 to 59.72
|
SECONDARY outcome
Timeframe: Weeks 2 to 13Population: Full analysis set
iPTH control was defined as a ≥ 50% reduction from baseline. iPTH was measured before the first dialysis session of the week, each week during the treatment phase and analyzed by the central laboratory.
Outcome measures
| Measure |
Paricalcitol
n=127 Participants
Participants received paricalcitol at an initial dose of 2 µg, and maxacalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 1 µg based on protocol-specified criteria up to a maximum of 7 µg.
|
Maxacalcitol
n=128 Participants
Participants received maxacalcitol at an initial dose of 5 µg (iPTH \< 500 pg/mL at Screening) or 10 µg (iPTH ≥ 500 pg/mL at Screening), and paricalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 2.5 µg based on protocol-specified criteria up to a maximum of 20 µg.
|
|---|---|---|
|
Number of Visits at Which Participants Achieved iPTH Control With ≥ 50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline
|
3.9 visits
Standard Deviation 2.97
|
5.3 visits
Standard Deviation 3.17
|
SECONDARY outcome
Timeframe: Weeks 2 to 13Population: Full analysis set
iPTH control was defined as being within the target range of 60 to 180 pg/mL. iPTH was measured before the first dialysis session of the week, once a week during the treatment phase and analyzed by the central laboratory.
Outcome measures
| Measure |
Paricalcitol
n=127 Participants
Participants received paricalcitol at an initial dose of 2 µg, and maxacalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 1 µg based on protocol-specified criteria up to a maximum of 7 µg.
|
Maxacalcitol
n=128 Participants
Participants received maxacalcitol at an initial dose of 5 µg (iPTH \< 500 pg/mL at Screening) or 10 µg (iPTH ≥ 500 pg/mL at Screening), and paricalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 2.5 µg based on protocol-specified criteria up to a maximum of 20 µg.
|
|---|---|---|
|
Number of Visits at Which Participants Achieved iPTH Control in the Target Range of 60 to 180 pg/mL
|
2.6 visits
Standard Deviation 2.51
|
3.4 visits
Standard Deviation 2.84
|
Adverse Events
Paricalcitol
Serious events: 10 serious events
Other events: 118 other events
Deaths: 0 deaths
Maxacalcitol
Serious events: 15 serious events
Other events: 123 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Paricalcitol
n=127 participants at risk
Participants received paricalcitol at an initial dose of 2 µg, and maxacalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 1 µg based on protocol-specified criteria up to a maximum of 7 µg.
|
Maxacalcitol
n=128 participants at risk
Participants received maxacalcitol at an initial dose of 5 µg (iPTH \< 500 pg/mL at Screening) or 10 µg (iPTH ≥ 500 pg/mL at Screening), and paricalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 2.5 µg based on protocol-specified criteria up to a maximum of 20 µg.
|
|---|---|---|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/127
|
0.78%
1/128
|
|
Cardiac disorders
Sinus bradycardia
|
0.79%
1/127
|
0.00%
0/128
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/127
|
0.78%
1/128
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/127
|
0.78%
1/128
|
|
Endocrine disorders
Parathyroid gland enlargement
|
0.00%
0/127
|
0.78%
1/128
|
|
Eye disorders
Cataract
|
0.00%
0/127
|
0.78%
1/128
|
|
Gastrointestinal disorders
Colonic polyp
|
0.00%
0/127
|
0.78%
1/128
|
|
Gastrointestinal disorders
Gastric ulcer haemorrhage
|
0.79%
1/127
|
0.00%
0/128
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.79%
1/127
|
0.00%
0/128
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/127
|
1.6%
2/128
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/127
|
0.78%
1/128
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
0.79%
1/127
|
0.00%
0/128
|
|
Injury, poisoning and procedural complications
Shunt malfunction
|
0.00%
0/127
|
0.78%
1/128
|
|
Injury, poisoning and procedural complications
Shunt occlusion
|
0.00%
0/127
|
1.6%
2/128
|
|
Injury, poisoning and procedural complications
Shunt stenosis
|
1.6%
2/127
|
0.78%
1/128
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.79%
1/127
|
0.00%
0/128
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.00%
0/127
|
0.78%
1/128
|
|
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis
|
0.00%
0/127
|
0.78%
1/128
|
|
Musculoskeletal and connective tissue disorders
Trigger finger
|
0.79%
1/127
|
0.00%
0/128
|
|
Nervous system disorders
Carpal tunnel syndrome
|
0.00%
0/127
|
0.78%
1/128
|
|
Nervous system disorders
Dizziness
|
0.00%
0/127
|
0.78%
1/128
|
|
Nervous system disorders
Headache
|
0.00%
0/127
|
0.78%
1/128
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/127
|
0.78%
1/128
|
|
Nervous system disorders
Thalamus haemorrhage
|
0.79%
1/127
|
0.00%
0/128
|
|
Renal and urinary disorders
Renal disorder in pregnancy
|
0.00%
0/127
|
0.78%
1/128
|
|
Reproductive system and breast disorders
Prostatitis
|
0.79%
1/127
|
0.00%
0/128
|
Other adverse events
| Measure |
Paricalcitol
n=127 participants at risk
Participants received paricalcitol at an initial dose of 2 µg, and maxacalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 1 µg based on protocol-specified criteria up to a maximum of 7 µg.
|
Maxacalcitol
n=128 participants at risk
Participants received maxacalcitol at an initial dose of 5 µg (iPTH \< 500 pg/mL at Screening) or 10 µg (iPTH ≥ 500 pg/mL at Screening), and paricalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 2.5 µg based on protocol-specified criteria up to a maximum of 20 µg.
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
7.9%
10/127
|
5.5%
7/128
|
|
Gastrointestinal disorders
Diarrhoea
|
8.7%
11/127
|
4.7%
6/128
|
|
Gastrointestinal disorders
Vomiting
|
8.7%
11/127
|
5.5%
7/128
|
|
Infections and infestations
Nasopharyngitis
|
33.9%
43/127
|
38.3%
49/128
|
|
Injury, poisoning and procedural complications
Contusion
|
6.3%
8/127
|
5.5%
7/128
|
|
Injury, poisoning and procedural complications
Excoriation
|
7.1%
9/127
|
1.6%
2/128
|
|
Injury, poisoning and procedural complications
Procedural hypotension
|
11.0%
14/127
|
15.6%
20/128
|
|
Injury, poisoning and procedural complications
Shunt stenosis
|
7.1%
9/127
|
4.7%
6/128
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
39.4%
50/127
|
43.0%
55/128
|
|
Metabolism and nutrition disorders
Hyperphosphataemia
|
16.5%
21/127
|
13.3%
17/128
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.5%
7/127
|
4.7%
6/128
|
|
Vascular disorders
Hypertension
|
15.7%
20/127
|
14.8%
19/128
|
Additional Information
Global Medical Services
Abbvie (prior sponsor, Abbott)
Phone: 800-633-9110
Results disclosure agreements
- Principal investigator is a sponsor employee AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
- Publication restrictions are in place
Restriction type: OTHER