Evaluation of the Effectiveness of Paricalcitol Versus Cinacalcet With Low-Dose Vitamin D (IMPACT SHPT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Abbott
ClinicalTrials.gov Identifier:
NCT00977080
First received: September 14, 2009
Last updated: May 18, 2012
Last verified: May 2012
  Purpose

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


Condition Intervention Phase
Chronic Kidney Disease
Secondary Hyperparathyroidism
Hemodialysis
Drug: Paricalcitol
Drug: Cinacalcet
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Abbott:

Primary Outcome Measures:
  • 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). [ Time Frame: Weeks 21 to 28 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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). [ Time Frame: Weeks 21 to 28 ] [ Designated as safety issue: No ]
    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.

  • 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). [ Time Frame: Weeks 21 to 28 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Weeks 21 to 28 ] [ Designated as safety issue: No ]
    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.

  • 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) [ Time Frame: Weeks 21 to 28 ] [ Designated as safety issue: Yes ]
    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.

  • 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) [ Time Frame: Weeks 21 to 28 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 272
Study Start Date: November 2009
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: IV Paricalcitol
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
Paricalcitol dosed per label by region (participants were to receive cinacalcet if they developed hypercalcemia)
Other Names:
  • ABT-358
  • paricalcitol
  • Zemplar
Active Comparator: Cinacalcet (at sites with IV paricalcitol)
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
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)
Other Names:
  • Sensipar
  • Mimpara
  • Hectorol
Active Comparator: Oral paricalcitol
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
Paricalcitol dosed per label by region (participants were to receive cinacalcet if they developed hypercalcemia)
Other Names:
  • ABT-358
  • paricalcitol
  • Zemplar
Active Comparator: Cinacalcet (at sites with oral paricalcitol)
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
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)
Other Names:
  • Sensipar
  • Mimpara
  • Hectorol

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Male or female patients >= 18 years old.
  2. 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.
  3. 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.
  4. 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

  1. Patient had a history of parathyroidectomy.
  2. 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.
  3. 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.
  4. Patient was known to be human immunodeficiency (HIV) positive.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00977080

  Show 83 Study Locations
Sponsors and Collaborators
Abbott
Investigators
Study Director: Samina Khan, MD Abbott
  More Information

No publications provided by Abbott

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Abbott
ClinicalTrials.gov Identifier: NCT00977080     History of Changes
Other Study ID Numbers: M10-967, 2009-011378-14
Study First Received: September 14, 2009
Results First Received: May 18, 2012
Last Updated: May 18, 2012
Health Authority: Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Italy: Ethics Committee
Italy: Ministry of Health
Italy: The Italian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Portugal: National Pharmacy and Medicines Institute
Russia: Ministry of Health of the Russian Federation
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Abbott:
Zemplar
paricalcitol
IMPACT SHPT
Hemodialysis
Chronic Kidney Disease Stage 5

Additional relevant MeSH terms:
Hyperparathyroidism
Hyperparathyroidism, Secondary
Kidney Diseases
Renal Insufficiency, Chronic
Parathyroid Diseases
Endocrine System Diseases
Urologic Diseases
Renal Insufficiency
Vitamin D
Ergocalciferols
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on August 26, 2014