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

NCT00977080 | Completed Phase 4 Results

• 2 other identifiers: M10-9672009-011378-14
• Study Type: interventional
• Target: 272
• Locations: 12 countries
• Sites: 83

Brief Summary

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

Conditions

Chronic Kidney Disease; Secondary Hyperparathyroidism; Hemodialysis

Keywords

Zemplar; paricalcitol; IMPACT SHPT; Hemodialysis; Chronic Kidney Disease Stage 5

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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).

  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).

  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

  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)

  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)

  Weeks 21 to 28

Study Arms (4)

IV Paricalcitol

ACTIVE COMPARATOR

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

Cinacalcet (at sites with IV paricalcitol)

ACTIVE COMPARATOR

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

Oral paricalcitol

ACTIVE COMPARATOR

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

Cinacalcet (at sites with oral paricalcitol)

ACTIVE COMPARATOR

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

Interventions

Paricalcitol DRUG

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

Also known as: ABT-358, Zemplar

IV Paricalcitol; Oral paricalcitol

Cinacalcet DRUG

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)

Also known as: Sensipar, Mimpara, Hectorol

Cinacalcet (at sites with IV paricalcitol); Cinacalcet (at sites with oral paricalcitol)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Abbott: lead

Study Sites (83)

Site Reference ID/Investigator# 22781

Tempe, Arizona, 85284, United States

Location

Site Reference ID/Investigator# 24342

Chula Vista, California, 91910, United States

Location

Site Reference ID/Investigator# 21142

Los Angeles, California, 90033, United States

Location

Site Reference ID/Investigator# 22762

Los Angeles, California, 90048, United States

Location

Site Reference ID/Investigator# 22758

Riverside, California, 92505, United States

Location

Site Reference ID/Investigator# 21442

San Diego, California, 92123, United States

Location

Site Reference ID/Investigator# 23688

Arvada, Colorado, 80002, United States

Location

Site Reference ID/Investigator# 21370

Coral Springs, Florida, 33071, United States

Location

Site Reference ID/Investigator# 25902

Hudson, Florida, 34667, United States

Location

Site Reference ID/Investigator# 21146

Lauderdale Lakes, Florida, 33313, United States

Location

Site Reference ID/Investigator# 26743

Lauderdale Lakes, Florida, 33313, United States

Location

Site Reference ID/Investigator# 22788

Miami, Florida, 33173, United States

Location

Site Reference ID/Investigator# 22722

Orlando, Florida, 32806, United States

Location

Site Reference ID/Investigator# 23147

Tampa, Florida, 33614, United States

Location

Site Reference ID/Investigator# 22778

Meridian, Idaho, 83642, United States

Location

Site Reference ID/Investigator# 21369

Detroit, Michigan, 48202, United States

Location

Site Reference ID/Investigator# 22786

Detroit, Michigan, 48236, United States

Location

Site Reference ID/Investigator# 21144

St Louis, Missouri, 63110, United States

Location

Site Reference ID/Investigator# 21443

St Louis, Missouri, 63110, United States

Location

Site Reference ID/Investigator# 21145

Omaha, Nebraska, 68131, United States

Location

Site Reference ID/Investigator# 22505

Flushing, New York, 11355, United States

Location

Site Reference ID/Investigator# 22759

Toledo, Ohio, 43606, United States

Location

Site Reference ID/Investigator# 22796

Lancaster, Pennsylvania, 17604, United States

Location

Site Reference ID/Investigator# 22770

Philadelphia, Pennsylvania, 19106, United States

Location

Site Reference ID/Investigator# 22772

Aiken, South Carolina, 29801, United States

Location

Site Reference ID/Investigator# 21147

Orangeburg, South Carolina, 29115, United States

Location

Site Reference ID/Investigator# 22982

Houston, Texas, 77030, United States

Location

Site Reference ID/Investigator# 21143

Houston, Texas, 77099, United States

Location

Site Reference ID/Investigator# 22506

San Antonio, Texas, 78215, United States

Location

Site Reference ID/Investigator# 22776

Bluefield, West Virginia, 24701, United States

Location

Site Reference ID/Investigator# 22311

Brno, 65691, Czechia

Location

Site Reference ID/Investigator# 22310

Jilemnice, 51415, Czechia

Location

Site Reference ID/Investigator# 21624

Ústí nad Labem, 40113, Czechia

Location

Site Reference ID/Investigator# 22363

Aalborg, 9000, Denmark

Location

Site Reference ID/Investigator# 23105

Copenhagen, 2100, Denmark

Location

Site Reference ID/Investigator# 23909

Fredericia, 7000, Denmark

Location

Site Reference ID/Investigator# 22462

Holstebro, 7500, Denmark

Location

Site Reference ID/Investigator# 21748

Coburg, 96450, Germany

Location

Site Reference ID/Investigator# 33268

Darmstadt, 64295, Germany

Location

Site Reference ID/Investigator# 35903

Düsseldorf, 40210, Germany

Location

Site Reference ID/Investigator# 21742

Frankfurt, 60590, Germany

Location

Site Reference ID/Investigator# 21744

Heilbronn, 74076, Germany

Location

Site Reference ID/Investigator# 21368

Lüdenscheid, 58515, Germany

Location

Site Reference ID/Investigator# 22362

Athens, 11528, Greece

Location

Site Reference ID/Investigator# 38970

Thessaloniki, 546 36, Greece

Location

Site Reference ID/Investigator# 22322

Thessaloniki, 54636, Greece

Location

Site Reference ID/Investigator# 22463

Thessaloniki, 54642, Greece

Location

Site Reference ID/Investigator# 22323

Thessaloniki, 56403, Greece

Location

Site Reference ID/Investigator# 39262

Thessaloniki, 570 01, Greece

Location

Site Reference ID/Investigator# 22312

Bergamo, 24128, Italy

Location

Site Reference ID/Investigator# 21746

Genova, 16132, Italy

Location

Site Reference ID/Investigator# 39180

Lucca, 55100, Italy

Location

Site Reference ID/Investigator# 22314

Milan, 20122, Italy

Location

Site Reference ID/Investigator# 21367

Pavia, 27100, Italy

Location

Site Reference ID/Investigator# 21745

Pesaro, 61100, Italy

Location

Site Reference ID/Investigator# 21842

Alkmaar, 1815 JD, Netherlands

Location

Site Reference ID/Investigator# 22309

Delft, 2625 AD, Netherlands

Location

Site Reference ID/Investigator# 21843

Dordrecht, 3317 NM, Netherlands

Location

Site Reference ID/Investigator# 38903

Beja, 7800-309, Portugal

Location

Site Reference ID/Investigator# 38531

Faro, 8005- 546, Portugal

Location

Site Reference ID/Investigator# 22464

Lisbon, 1750-130, Portugal

Location

Site Reference ID/Investigator# 23910

Vila Franca de Xira, 2600-076, Portugal

Location

Site Reference ID/Investigator# 24643

Moscow, 123182, Russia

Location

Site Reference ID/Investigator# 24642

Moscow, 125284, Russia

Location

Site Reference ID/Investigator# 21361

Barcelona, 08025, Spain

Location

Site Reference ID/Investigator# 21364

Córdoba, 14004, Spain

Location

Site Reference ID/Investigator# 22366

L'Hospitalet, Barcelona, 08097, Spain

Location

Site Reference ID/Investigator# 38343

Madrid, 28040, Spain

Location

Site Reference ID/Investigator# 21362

Madrid, 28041, Spain

Location

Site Reference ID/Investigator# 21363

Palma de Mallorca, 07014, Spain

Location

Site Reference ID/Investigator# 22367

Pamplona, 31008, Spain

Location

Site Reference ID/Investigator# 38462

Puerto de la Cruz, 38400, Spain

Location

Site Reference ID/Investigator# 21365

Seville, 41007, Spain

Location

Site Reference ID/Investigator# 23913

Linköping, 58185, Sweden

Location

Site Reference ID/Investigator# 23782

Stockholm, 182 88, Sweden

Location

Site Reference ID/Investigator# 22364

Uppsala, 751 85, Sweden

Location

Site Reference ID/Investigator# 23912

Birmingham, B18 7QH, United Kingdom

Location

Site Reference ID/Investigator# 21747

Coventry, CV2 2DX, United Kingdom

Location

Site Reference ID/Investigator# 23102

London, NW3 2PF, United Kingdom

Location

Site Reference ID/Investigator# 23104

London, SE1 9RT, United Kingdom

Location

Site Reference ID/Investigator# 23103

Manchester, M6 8HD, United Kingdom

Location

Site Reference ID/Investigator# 41982

Omagh, Northern Ireland, BT79 0AP, United Kingdom

Location

Site Reference ID/Investigator# 40222

Sheffield, S5 7AU, United Kingdom

Location

Related Publications (3)

• Cozzolino M, Ketteler M, Martin KJ, Sharma A, Goldsmith D, Khan S. Paricalcitol- or cinacalcet-centred therapy affects markers of bone mineral disease in patients with secondary hyperparathyroidism receiving haemodialysis: results of the IMPACT-SHPT study. Nephrol Dial Transplant. 2014 Apr;29(4):899-905. doi: 10.1093/ndt/gfu011. Epub 2014 Feb 4.

  PMID: 24500308 DERIVED

• Sharma A, Marshall TS, Khan SS, Johns B. Cost effectiveness of paricalcitol versus cinacalcet with low-dose vitamin D for management of secondary hyperparathyroidism in haemodialysis patients in the USA. Clin Drug Investig. 2014 Feb;34(2):107-15. doi: 10.1007/s40261-013-0151-4.

  PMID: 24214232 DERIVED

• Ketteler M, Martin KJ, Wolf M, Amdahl M, Cozzolino M, Goldsmith D, Sharma A, Marx S, Khan S. Paricalcitol versus cinacalcet plus low-dose vitamin D therapy for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis: results of the IMPACT SHPT study. Nephrol Dial Transplant. 2012 Aug;27(8):3270-8. doi: 10.1093/ndt/gfs018. Epub 2012 Mar 2.

  PMID: 22387567 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Hyperparathyroidism, Secondary

Interventions

paricalcitol; Cinacalcet; 1 alpha-hydroxyergocalciferol

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hyperparathyroidism; Parathyroid Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Limitations and Caveats

Using a fixed dosing algorithm based on biochemical criteria may affect interpretation of the results. In the future, the risk/benefit profile of these interventions should be assessed by longer-term clinical outcomes.

Results Point of Contact

• Title: Global Medical Services
• Organization: Abbott

800-633-9110

Study Officials

• Samina Khan, MD

  Abbott

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2009
• First Posted: September 15, 2009
• Study Start: November 1, 2009
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: June 20, 2012
• Results First Posted: June 20, 2012

Record last verified: 2012-05

Locations

SE (3); DE (6); RU (2); ES (9); US (30); GB (7); IT (6); CZ (3); DK (4); NL (3); PT (4); GR (6)