Evaluation of the Effectiveness of Paricalcitol Versus Cinacalcet With Low-Dose Vitamin D

Study Overview
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Brief Summary
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Evaluates the effectiveness of on-label Paricalcitol versus Cinacalcet with Low-Dose Vitamin D.

Detailed Description
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During a 4-week washout period, participants stopped taking cinacalcet or other vitamin D receptor activators (VDRAs). (Participants who were naive to cinacalcet or VDRAs did not have to wash out). At randomization, participants entered a 28-week open-label treatment period, during which they received either cinacalcet or paricalcitol. Participants who were assigned to receive paricalcitol were dosed according to the approved label in their respective geographic regions (i.e., IV at sites in the US and Russia and oral at sites in Europe). Supplemental cinacalcet was administered to participants in the paricalcitol arms who developed hypercalcemia (defined as >= 10.5 mg/dL). The evaluation period was from Weeks 21 to 28.

Official Title
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The IMPACT SHPT Study: Study to Evaluate the Improved Management of iPTH With Paricalcitol-centered Therapy vs. Cinacalcet Therapy With Low-dose Vitamin D in Hemodialysis Patients With Secondary Hyperparathyroidism

Conditions
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Chronic Kidney Disease, Secondary Hyperparathyroidism, Hemodialysis

Intervention / Treatment
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* Drug: Paricalcitol
* Drug: Cinacalcet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Male or female patients >= 18 years old. Patient was diagnosed with Stage 5 chronic kidney disease (CKD) and had been receiving intravenous (IV) or oral vitamin D receptor activators (VDRAs) or cinacalcet during the 8 weeks prior to the screening period or naïve patients who had not received VDRA or cinacalcet within 8 weeks of screening. Patient was on maintenance HD (hemodialysis) 3 times weekly (TIW) for at least 3 months prior to screening and was expected to remain on HD for the duration of the study. For entry into the Pre-Treatment Washout Period (for patients who were not naïve to VDRAs and cinacalcet), the patient had to have screening laboratory values of: iPTH level 130 to 700 pg/mL Serum Total Alkaline Phosphatase level >= 40 U/L Calcium level <= 10.0 mg/dL (2.49 mmol/L) Calcium-phosphorus product (CaxP) <= 75 mg2/dL2 (US) and <= 70 mg2/dL2 (non-US) Exclusion Criteria Patient had a history of parathyroidectomy. Patient had a current malignancy (with the exception of basal or squamous cell carcinoma of the skin), or clinically significant liver disease, in the opinion of the investigator. Use of known inhibitors (i.e., ketoconazole) or inducers (i.e., carbamazepine) of cytochrome P450 (including grapefruit and/or grapefruit juice) 3A (CYP3A) or drugs metabolized by cytochrome P450 2D6 (CYP2D6) (e.g., flecainide, vinblastine, thioridazine, and most tricyclic antidepressants) within 2 weeks prior to study drug administration. Commonly used beta blockers such as metoprolol and carvedilol are allowed but are metabolized by CYP2D6; thus, an adjustment to a lower dose may have been required. Patient was known to be human immunodeficiency (HIV) positive.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: IV Paricalcitol<br>Participants in the IV stratum received intravenous (IV) paricalcitol and, if hypercalcemia (calcium >= 10.5 mg/dL), received 30 mg of oral cinacalcet. Paricalcitol was dosed at 0.07 mcg/kg with titration every 2 weeks. | Drug: Paricalcitol<br>* Paricalcitol dosed per label by region (participants were to receive cinacalcet if they developed hypercalcemia)<br>* Other names: Zemplar;|
| Active Comparator: Cinacalcet (at sites with IV paricalcitol)<br>Participants in the IV stratum received 30 mg of oral cinacalcet daily with a low-dose vitamin D receptor activator (VDRA) (doxercalciferol IV 1 mcg 3 times weekly (TIW) at sites in the US and alfacalcidol capsules 0.25 mcg daily at sites in Russia). | Drug: Cinacalcet<br>* On-label oral cinacalcet by region with low dose vitamin D receptor activator (VDRA) (either doxercalciferol at US sites or alfacalcidol at non-US sites)<br>* Other names: Hectorol;|
| Active Comparator: Oral paricalcitol<br>Participants in the oral stratum received oral paricalcitol and, if hypercalcemia (calcium >= 10.5 mg/dL), received 30 mg of oral cinacalcet. Paricalcitol was dosed at mcg = IPTH/60 3 times weekly (TIW) with titration every 2 weeks. | Drug: Paricalcitol<br>* Paricalcitol dosed per label by region (participants were to receive cinacalcet if they developed hypercalcemia)<br>* Other names: Zemplar;|
| Active Comparator: Cinacalcet (at sites with oral paricalcitol)<br>Participants in the oral stratum received 30 mg of oral cinacalcet daily with a low-dose vitamin D receptor activator (VDRA) (alfacalcidol capsules 0.25 mcg daily). | Drug: Cinacalcet<br>* On-label oral cinacalcet by region with low dose vitamin D receptor activator (VDRA) (either doxercalciferol at US sites or alfacalcidol at non-US sites)<br>* Other names: Hectorol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants Who Achieve a Mean Intact Parathyroid Hormone (iPTH) Value Between 150 to 300 pg/mL During the Evaluation Period (Weeks 21 to 28). | iPTH values obtained during the evaluation period (Weeks 21 to 28) were averaged for each participant with at least 2 iPTH values. Participants whose average iPTH value was between 150 to 300 pg/mL were counted. | Weeks 21 to 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieve at Least 30% Reduction From Baseline in Intact Parathyroid Hormone (iPTH) as Assessed by the Mean iPTH Obtained During the Evaluation Period (Weeks 21 to 28). | iPTH values obtained during the evaluation period (Weeks 21 to 28) were averaged for each participant with both a baseline iPTH value and at least 2 iPTH values. Participants whose average iPTH value showed a 30% reduction from Baseline were counted. | Weeks 21 to 28 | 
| Number of Participants Who Achieve at Least 50% Reduction From Baseline in iPTH as Assessed by the Mean iPTH Obtained During the Evaluation Period (Weeks 21 to 28). | iPTH values obtained during the evaluation period (Weeks 21 to 28) were averaged for each participant with both a baseline iPTH value and at least 2 iPTH values. Participants whose average iPTH value showed a 50% reduction from Baseline were counted. | Weeks 21 to 28 | 
| Analysis of the Number of Participants Who Achieve a Mean iPTH Value Between 150 and 300 pg/mL During the Evaluation Period (Weeks 21 to 28) Using a Cochran-Mantel-Haenszel Test Controlling for IV and Oral Site Randomization Strata | iPTH values obtained during the evaluation period (Weeks 21 to 28) were averaged for each participant with at least 2 iPTH values. Participants whose average iPTH value was between 150 to 300 pg/mL were counted. Data from both the IV and oral strata were analyzed together. | Weeks 21 to 28 | 
| Number of Participants With Hypocalcemia Defined as < 8.4 mg/dL and Based on the Mean of at Least 2 Values Obtained During the Evaluation Period (Weeks 21 to 28) | Calcium values obtained during the evaluation period (Weeks 21 to 28) were averaged for each participant with at least 2 calcium values. Participants whose average calcium value was < 8.4 mg/dL were counted. | Weeks 21 to 28 | 
| Number of Participants With Hypercalcemia Defined as Calcium > 10.5 mg/dL and Based on the Mean of at Least 2 Values Obtained During the Evaluation Period (Weeks 21 to 28) | Calcium values obtained during the evaluation period (Weeks 21 to 28) were averaged for each participant with at least 2 calcium values. Participants whose average calcium value was > 10.5 mg/dL were counted. | Weeks 21 to 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Zemplar, paricalcitol, IMPACT SHPT, Hemodialysis, Chronic Kidney Disease Stage 5