E.V.O.L.V.E. Trial™: EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events - Full Text View

Sponsored by:	Amgen
Information provided by:	Amgen
ClinicalTrials.gov Identifier:	NCT00345839

Purpose

The purpose of this study is to evaluate the effects of cinacalcet (cinacalcet HCl or Sensipar®/Mimpara®) on cardiovascular events and death in chronic kidney disease (CKD) patients with secondary hyperparathyroidism (HPT) who are receiving dialysis.

Condition	Intervention	Phase
Secondary Hyperparathyroidism Chronic Kidney Disease	Drug: Cinacalcet Drug: Sensipar (Cinacalcet HCl) Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Safety/Efficacy Study
Official Title:	EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events

Resource links provided by NLM:

MedlinePlus related topics: Kidney Failure

Drug Information available for: Cinacalcet Cinacalcet hydrochloride

U.S. FDA Resources

Further study details as provided by Amgen:

Primary Outcome Measures:

Time to the composite event comprising all-cause mortality or non-fatal cardiovascular events (MI, hospitalization for unstable angina, HF, or peripheral vascular event) [ Time Frame: estimated 2.5 to 4 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Time to all-cause mortality [ Time Frame: estimated 2.5 to 4 years ] [ Designated as safety issue: No ]
Time to cardiovascular mortality [ Time Frame: estimated 2.5 to 4 years ] [ Designated as safety issue: No ]
Time to fatal and non-fatal MI [ Time Frame: estimated 2.5 to 4 years ] [ Designated as safety issue: Yes ]
Time to fatal and non-fatal hospitalization for unstable angina [ Time Frame: estimated 2.5 to 4 years ] [ Designated as safety issue: Yes ]
Time to fatal and non-fatal HF event [ Time Frame: estimated 2.5 to 4 years ] [ Designated as safety issue: Yes ]
Time to fatal and non-fatal peripheral vascular event [ Time Frame: estimated 2.5 to 4 years ] [ Designated as safety issue: Yes ]
Time to fatal and non-fatal stroke [ Time Frame: estimated 2.5 to 4 years ] [ Designated as safety issue: Yes ]
Time to bone fracture [ Time Frame: estimated 2.5 to 4 years ] [ Designated as safety issue: Yes ]
Time to parathyroidectomy [ Time Frame: estimated 2.5 to 4 years ] [ Designated as safety issue: Yes ]

Enrollment:	3883
Study Start Date:	September 2006
Estimated Study Completion Date:	November 2010
Estimated Primary Completion Date:	August 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Cinacalcet: Experimental	Drug: Cinacalcet Possible doses: 30, 60, 90, 120, and 180 mg using tablet strengths of 30, 60, or 90 mg. Sequential titration starting at 30 mg QD, once every 4 weeks for the first 20 weeks and once every 8 weeks after Week 20. Titration increases or decreases based on PTH values, serum calcium, and safety. Daily dosing unless temporary hold criteria or withdrawal criteria is met, or until study completion; estimated 2.5 to 4 years of intervention. Drug: Sensipar (Cinacalcet HCl) Possible doses: 30, 60, 90, 120, and 180 mg using tablet strengths of 30, 60, or 90 mg. Sequential titration starting at 30 mg QD, once every 4 weeks for the first 20 weeks and once every 8 weeks after Week 20. Titration increases or decreases based on PTH values, serum calcium, and safety. Daily dosing unless temporary hold criteria or withdrawal criteria is met, or until study completion; estimated 2.5 to 4 years of intervention.
Placebo: Placebo Comparator	Drug: Placebo Possible doses: 30, 60, 90, 120, and 180 mg using tablet strengths of 30, 60, or 90 mg. Sequential titration starting at 30 mg QD, once every 4 weeks for the first 20 weeks and once every 8 weeks after Week 20. Titration increases or decreases based on PTH values, serum calcium, and safety. Daily dosing unless temporary hold criteria or withdrawal criteria is met, or until study completion; estimated 2.5 to 4 years of intervention.

Arms

Assigned Interventions

Cinacalcet: Experimental

Drug: Cinacalcet

Possible doses: 30, 60, 90, 120, and 180 mg using tablet strengths of 30, 60, or 90 mg. Sequential titration starting at 30 mg QD, once every 4 weeks for the first 20 weeks and once every 8 weeks after Week 20.

Titration increases or decreases based on PTH values, serum calcium, and safety. Daily dosing unless temporary hold criteria or withdrawal criteria is met, or until study completion; estimated 2.5 to 4 years of intervention.

Drug: Sensipar (Cinacalcet HCl)

Possible doses: 30, 60, 90, 120, and 180 mg using tablet strengths of 30, 60, or 90 mg. Sequential titration starting at 30 mg QD, once every 4 weeks for the first 20 weeks and once every 8 weeks after Week 20.

Titration increases or decreases based on PTH values, serum calcium, and safety. Daily dosing unless temporary hold criteria or withdrawal criteria is met, or until study completion; estimated 2.5 to 4 years of intervention.

Placebo: Placebo Comparator

Drug: Placebo

Possible doses: 30, 60, 90, 120, and 180 mg using tablet strengths of 30, 60, or 90 mg. Sequential titration starting at 30 mg QD, once every 4 weeks for the first 20 weeks and once every 8 weeks after Week 20.

Titration increases or decreases based on PTH values, serum calcium, and safety. Daily dosing unless temporary hold criteria or withdrawal criteria is met, or until study completion; estimated 2.5 to 4 years of intervention.

Detailed Description:

Secondary HPT is common in people with CKD. Patients with secondary HPT often have high parathyroid hormone (PTH) levels and may develop large parathyroid glands in the neck. Patients with secondary HPT may have bone disease (osteodystrophy). This bone disease may cause bone pain, fractures, and poor formation of red blood cells. Other problems from secondary HPT may include increases in blood levels of calcium and phosphorus. These may cause calcium to deposit in body tissues. Calcium deposits can cause arthritis (joint pain and swelling), muscle inflammation, itching, gangrene (death of soft tissue), or heart and lung problems. New evidence suggests that secondary HPT is associated with cardiovascular disease and increased death risk. The purpose of this study is to evaluate the effects of cinacalcet (cinacalcet HCl or Sensipar®/Mimpara®) on cardiovascular events (having to do with the heart and its blood vessels) and death in chronic kidney disease (CKD) patients with secondary hyperparathyroidism (HPT) who are receiving dialysis. These events include death from any reason, heart attack and episodes where the heart does not get enough oxygen, peripheral vascular disease (narrowing of vessels that carry blood to the legs, arms, stomach or kidneys), and heart failure (a condition that occurs when the heart is unable to pump enough blood to meet the need's of the body's tissues)

Eligibility

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

Criteria

Inclusion Criteria:

Inclusion:≥ 18 years of age
Treated with maintenance hemodialysis - PTH ≥ 300 pg/mL (31.8 pmol/L)
serum calcium ≥ 8.4mg/dL (2.1 mmol/L)
Ca x P ≥ 45 mg2/dL2 (3.63 mmol2/L2)

Exclusion Criteria: - Exclusion:

Parathyroidectomy in the 12 weeks before the date of informed consent
Received therapy with cinacalcet within 3 months of randomization
Hospitalization within 12 weeks of randomization for any of the following events: a. Myocardial ischemia b.

Unstable angina c. HF (including any unplanned presentation to a health care facility that would require mechanical intervention [i.e., unplanned dialysis treatment]) d. Peripheral vascular disease (other than dialysis vascular access revision) e. Stroke

History of seizure within 12 weeks prior to randomization
Scheduled date for kidney transplant from a known living donor
Anticipated parathyroidectomy within 6 months after randomization

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00345839

Show 417 Study Locations

Sponsors and Collaborators

Amgen

Investigators

Study Director:

MD

Amgen

More Information

Additional Information:

AmgenTrials clinical trials website This link exits the ClinicalTrials.gov site

Publications:

Notenboom V, Hibbert RG, van Rossum-Fikkert SE, Olsen JV, Mann M, Sixma TK. Functional characterization of Rad18 domains for Rad6, ubiquitin, DNA binding and PCNA modification. Nucleic Acids Res. 2007;35(17):5819-30. Epub 2007 Aug 24.

Responsible Party:	Amgen Inc. ( Global Development Leader )
Study ID Numbers:	20050182
Study First Received:	June 27, 2006
Last Updated:	September 10, 2009
ClinicalTrials.gov Identifier:	NCT00345839 History of Changes
Health Authority:	CAN: HealthCanada; EU: Committee for Human Medicinal Products; Latin America/Russia: Ministry Of Health; United States: Food and Drug Administration

Keywords provided by Amgen:

Cinacalcet HCl
Cinacalcet
AMG 073
Sensipar
Mimpara

Calcimimetic
Hemodialysis
CKD
Secondary hyperparathyroidism (HPT)

Study placed in the following topic categories:

Parathyroid Diseases
Renal Insufficiency
Kidney Failure, Chronic
Endocrine System Diseases
Calcium, Dietary
Hyperparathyroidism, Secondary
Hyperparathyroidism

Urologic Diseases
Renal Insufficiency, Chronic
Neoplasm Metastasis
Kidney Diseases
Endocrinopathy
Kidney Failure

Additional relevant MeSH terms:

Parathyroid Diseases
Renal Insufficiency
Kidney Failure, Chronic
Endocrine System Diseases
Hyperparathyroidism, Secondary
Neoplastic Processes
Neoplasms

Pathologic Processes
Hyperparathyroidism
Urologic Diseases
Renal Insufficiency, Chronic
Neoplasm Metastasis
Kidney Diseases
Kidney Failure

ClinicalTrials.gov processed this record on September 11, 2009