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

Chronic Kidney Disease Clinical Trial

— IMPACT SHPT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00977080
• Other study ID #: M10-967
• Secondary ID: 2009-011378-14
• Status: Completed
• Phase: Phase 4
• First received: September 14, 2009
• Last updated: May 18, 2012
• Start date: November 2009
• Est. completion date: May 2011

Study information

• Verified date: May 2012
• Source: Abbott
• Contact: n/a
• Is FDA regulated: No
• Health authority: Czech Republic: State Institute for Drug ControlDenmark: Danish Medicines AgencyGermany: Federal Institute for Drugs and Medical DevicesGreece: National Organization of MedicinesItaly: Ethics CommitteeItaly: Ministry of HealthItaly: The Italian Medicines AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Portugal: National Pharmacy and Medicines InstituteRussia: Ministry of Health of the Russian FederationSpain: Spanish Agency of MedicinesSweden: Medical Products AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 272
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Hemodialysis
• Hyperparathyroidism
• Hyperparathyroidism, Secondary
• Kidney Diseases
• Renal Insufficiency, Chronic
• Secondary Hyperparathyroidism

Intervention

Drug:
• Paricalcitol
Paricalcitol dosed per label by region (participants were to receive cinacalcet if they developed hypercalcemia)
• 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)

Locations

Country	Name	City	State
Czech Republic	Site Reference ID/Investigator# 22311	Brno
Czech Republic	Site Reference ID/Investigator# 22310	Jilemnice
Czech Republic	Site Reference ID/Investigator# 21624	Usti nad Labem
Denmark	Site Reference ID/Investigator# 22363	Aalborg
Denmark	Site Reference ID/Investigator# 23105	Copenhagen
Denmark	Site Reference ID/Investigator# 23909	Fredericia
Denmark	Site Reference ID/Investigator# 22462	Holstebro
Germany	Site Reference ID/Investigator# 21748	Coburg
Germany	Site Reference ID/Investigator# 33268	Darmstadt
Germany	Site Reference ID/Investigator# 35903	Duesseldorf
Germany	Site Reference ID/Investigator# 21742	Frankfurt
Germany	Site Reference ID/Investigator# 21744	Heilbronn
Germany	Site Reference ID/Investigator# 21368	Luedenscheid
Greece	Site Reference ID/Investigator# 22362	Athens
Greece	Site Reference ID/Investigator# 22322	Thessaloniki
Greece	Site Reference ID/Investigator# 22323	Thessaloniki
Greece	Site Reference ID/Investigator# 22463	Thessaloniki
Greece	Site Reference ID/Investigator# 38970	Thessaloniki
Greece	Site Reference ID/Investigator# 39262	Thessaloniki
Italy	Site Reference ID/Investigator# 22312	Bergamo
Italy	Site Reference ID/Investigator# 21746	Genova
Italy	Site Reference ID/Investigator# 39180	Lucca
Italy	Site Reference ID/Investigator# 22314	Milan
Italy	Site Reference ID/Investigator# 21367	Pavia
Italy	Site Reference ID/Investigator# 21745	Pesaro
Netherlands	Site Reference ID/Investigator# 21842	Alkmaar
Netherlands	Site Reference ID/Investigator# 22309	Delft
Netherlands	Site Reference ID/Investigator# 21843	Dordrecht
Portugal	Site Reference ID/Investigator# 38903	Beja
Portugal	Site Reference ID/Investigator# 38531	Faro
Portugal	Site Reference ID/Investigator# 22464	Lisbon
Portugal	Site Reference ID/Investigator# 23910	Vila Franca de Xira
Russian Federation	Site Reference ID/Investigator# 24642	Moscow
Russian Federation	Site Reference ID/Investigator# 24643	Moscow
Spain	Site Reference ID/Investigator# 21361	Barcelona
Spain	Site Reference ID/Investigator# 21364	Cordoba
Spain	Site Reference ID/Investigator# 22366	L'Hospitalet, Barcelona
Spain	Site Reference ID/Investigator# 21362	Madrid
Spain	Site Reference ID/Investigator# 38343	Madrid
Spain	Site Reference ID/Investigator# 21363	Palma de Mallorca
Spain	Site Reference ID/Investigator# 22367	Pamplona
Spain	Site Reference ID/Investigator# 38462	Puerto de la Cruz
Spain	Site Reference ID/Investigator# 21365	Seville
Sweden	Site Reference ID/Investigator# 23913	Linkoping
Sweden	Site Reference ID/Investigator# 23782	Stockholm
Sweden	Site Reference ID/Investigator# 22364	Uppsala
United Kingdom	Site Reference ID/Investigator# 23912	Birmingham
United Kingdom	Site Reference ID/Investigator# 21747	Coventry
United Kingdom	Site Reference ID/Investigator# 23102	London
United Kingdom	Site Reference ID/Investigator# 23104	London
United Kingdom	Site Reference ID/Investigator# 23103	Manchester
United Kingdom	Site Reference ID/Investigator# 41982	Omagh, Northern Ireland
United Kingdom	Site Reference ID/Investigator# 40222	Sheffield
United States	Site Reference ID/Investigator# 22772	Aiken	South Carolina
United States	Site Reference ID/Investigator# 23688	Arvada	Colorado
United States	Site Reference ID/Investigator# 22776	Bluefield	West Virginia
United States	Site Reference ID/Investigator# 24342	Chula Vista	California
United States	Site Reference ID/Investigator# 21370	Coral Springs	Florida
United States	Site Reference ID/Investigator# 21369	Detroit	Michigan
United States	Site Reference ID/Investigator# 22786	Detroit	Michigan
United States	Site Reference ID/Investigator# 22505	Flushing	New York
United States	Site Reference ID/Investigator# 21143	Houston	Texas
United States	Site Reference ID/Investigator# 22982	Houston	Texas
United States	Site Reference ID/Investigator# 25902	Hudson	Florida
United States	Site Reference ID/Investigator# 22796	Lancaster	Pennsylvania
United States	Site Reference ID/Investigator# 21146	Lauderdale Lakes	Florida
United States	Site Reference ID/Investigator# 26743	Lauderdale Lakes	Florida
United States	Site Reference ID/Investigator# 21142	Los Angeles	California
United States	Site Reference ID/Investigator# 22762	Los Angeles	California
United States	Site Reference ID/Investigator# 22778	Meridian	Idaho
United States	Site Reference ID/Investigator# 22788	Miami	Florida
United States	Site Reference ID/Investigator# 21145	Omaha	Nebraska
United States	Site Reference ID/Investigator# 21147	Orangeburg	South Carolina
United States	Site Reference ID/Investigator# 22722	Orlando	Florida
United States	Site Reference ID/Investigator# 22770	Philadelphia	Pennsylvania
United States	Site Reference ID/Investigator# 22758	Riverside	California
United States	Site Reference ID/Investigator# 22506	San Antonio	Texas
United States	Site Reference ID/Investigator# 21442	San Diego	California
United States	Site Reference ID/Investigator# 21144	St. Louis	Missouri
United States	Site Reference ID/Investigator# 21443	St. Louis	Missouri
United States	Site Reference ID/Investigator# 23147	Tampa	Florida
United States	Site Reference ID/Investigator# 22781	Tempe	Arizona
United States	Site Reference ID/Investigator# 22759	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Abbott

Countries where clinical trial is conducted

United States,  Czech Republic,  Denmark,  Germany,  Greece,  Italy,  Netherlands,  Portugal,  Russian Federation,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes