Chronic Kidney Disease, Stage 5, Secondary Hyperparathyroidism
Conditions
Keywords
Stage 5 Chronic Kidney Disease (CKD)
Brief summary
The purpose of this study is to evaluate the effects of Zemplar® Injection and Hectorol® Injection on intestinal calcium absorption in Chronic Kidney Disease Stage 5 subjects on hemodialysis.
Interventions
DRUGZemplar® injection
6 mcg QOD
DRUGHectorol® injection
3.6 mcg QOD
Sponsors
Abbott
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is \>= 20 years of age. * Subject is diagnosed with CKD Stage 5, and must be on maintenance (chronic) hemodialysis (HD) three times a week for at least 2 months prior to the Screening Visit and expected to remain on HD for the duration of the study. * If female, subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or is of childbearing potential and practicing one of the following methods of birth control: * Condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD) * Contraceptives (oral or parenteral) for three months prior to study drug administration * In a monogamous relationship with a vasectomized partner * If female, subject is not breastfeeding and has a negative serum pregnancy test prior to the treatment phase. * Subject has an intact PTH value \> 200 pg/mL at Screening only (or Re-screening, if applicable). * Subject has a serum calcium level \< 10.2 mg/dL at Screening only (or Re-screening, if applicable). * Subject has a serum phosphorus level \< 6.5 mg/dL at Screening only (or Re-screening, if applicable). * Subject has a CaxP product \<= 65 at Screening only (or Re-screening, if applicable). * Subject must voluntarily sign and date an informed consent, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), prior to the conduct of any study-specific procedure.
Exclusion criteria
* Subject has a history of an allergic reaction or significant sensitivity to vitamin D or vitamin D related compounds. * Subject has chronic gastrointestinal disease, which in the Investigator's opinion, may result in clinically significant GI malabsorption. * Liver function defects defined as \> 2 times the upper limit of normal for liver enzyme (SGOT/AST, SGPT/ALT) levels. * Subject has a hemoglobin level \< 9.0 g/dL. * Subject is taking maintenance calcitonin, Sensipar® (cinacalcet), glucocorticoids in an equivalent dose \> 5 mg prednisone daily, or other drugs that may affect calcium or bone metabolism within 2 weeks prior to screening, other than females on stable (same dose and product for 3 months) estrogen and/or progestin therapy. * For any reason, subject is considered by the Investigator to be an unsuitable candidate to receive pharmacological doses of vitamin D. * Subject has received any investigational drug within 4 weeks prior to the Treatment Phase.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Calcium Absorption Fractions Analyzed by Analysis of Variance (ANOVA) | 42 Days | Calcium Absorption Fraction obtained at the end of Period 1 & Period 2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Calcium Absorption Fractions Analyzed by Mixed Model | 42 Days | Calcium Absorption Fraction obtained at the end of Period 1 & Period 2 |
Countries
United States
Participant flow
Pre-assignment details
Subjects assigned randomly in a 1:1 manner to Sequence Group I or II. Group I received Drug A (6 mcg Zemplar Injection QOD for 6 doses) in Period 1 and Drug B (3.6 mcg Hectorol Injection QOD for 6 doses) in Period 2. Each treatment period was 14 days and a 14 day washout separated the treatment periods.
Participants by arm
| Arm | Count |
|---|---|
| Zemplar First 6 mcg Zemplar Injection QOD for 6 doses in Period 1 and 3.6 mcg Hectorol Injection QOD for 6 doses in Period 2 | 21 |
| Hectorol First 3.6 mcg Hectorol Injection QOD for 6 doses in Period 1 and 6 mcg Zemplar Injection QOD for 6 doses in Period 2 | 20 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period: Second Intervention | Other | 2 | 1 |
| Period: Washout Period of Two Weeks | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Zemplar First | Hectorol First |
|---|---|---|---|
| Age Continuous | 55.0 years STANDARD_DEVIATION 10.34 | 54.3 years STANDARD_DEVIATION 11.03 | 55.6 years STANDARD_DEVIATION 9.81 |
| Age, Customized 40 - <60 years | 25 participants | 13 participants | 12 participants |
| Age, Customized <40 years | 3 participants | 2 participants | 1 participants |
| Age, Customized >=60 years | 13 participants | 6 participants | 7 participants |
| Calcium Absorption Fraction | 0.107 Fractions STANDARD_DEVIATION 0.0085 | 0.085 Fractions STANDARD_DEVIATION 0.0086 | 0.130 Fractions STANDARD_DEVIATION 0.0132 |
| Race/Ethnicity, Customized Hispanic | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized No ethnicity | 41 participants | 21 participants | 20 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 33 Participants | 18 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 3 Participants | 4 Participants |
| Region of Enrollment United States | 41 participants | 21 participants | 20 participants |
| Sex: Female, Male Female | 19 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 22 Participants | 15 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / — | 15 / — |
| serious Total, serious adverse events | 3 / — | 3 / — |
Outcome results
Primary
Calcium Absorption Fractions Analyzed by Analysis of Variance (ANOVA)
Calcium Absorption Fraction obtained at the end of Period 1 & Period 2
Time frame: 42 Days
Population: Per-Protocol Population - all subjects who completed both Period 1 and 2 and did not have major protocol violations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Zemplar | Calcium Absorption Fractions Analyzed by Analysis of Variance (ANOVA) | 0.103 Fractions | Standard Error 0.007 |
| Hectorol | Calcium Absorption Fractions Analyzed by Analysis of Variance (ANOVA) | 0.108 Fractions | Standard Error 0.007 |
Comparison: The null hypothesis was that there is no difference in mean calcium absorption between Zemplar and Hectorol. Approximately 42 subjects were to be randomized assuming 36 subjects would available in the per-protocol set. A sample size of 36 subjects has 80% power to detect a mean difference of -0.018 assuming the Zemplar group mean is 0.139, the Hectorol group mean is 0.157 and the STD is 0.037. The ANOVA model included effects for sequence, subject-within-sequence, period and treatment regimen.p-value: 0.57395% CI: [-0.024, 0.014]ANOVA
Secondary
Calcium Absorption Fractions Analyzed by Mixed Model
Calcium Absorption Fraction obtained at the end of Period 1 & Period 2
Time frame: 42 Days
Population: ITT Population -all randomized subjects who received at least one dose of study drug and were analyzed by the randomized treatment sequence assigned to each subject.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Zemplar | Calcium Absorption Fractions Analyzed by Mixed Model | 0.106 Fractions | Standard Error 0.011 |
| Hectorol | Calcium Absorption Fractions Analyzed by Mixed Model | 0.110 Fractions | Standard Error 0.011 |
Comparison: The null hypothesis was that there is no difference in the mean calcium absorption fraction between Zemplar Injection and Hectorol Injection. The power calculation applied to the primary efficacy analysis.p-value: 0.6795% CI: [-0.023, 0.015]Mixed Models Analysis