ACHIEVE: Optimizing the Treatment of Secondary Hyperparathyroidism

ACHIEVE: Optimizing the Treatment of Secondary Hyperparathyroidism: A Comparison of Sensipar® and Low Dose Vitamin D vs. Escalating Doses of Vitamin D Alone

The purpose of this study is to compare the proportion of chronic kidney disease (CKD) subjects on dialysis receiving Sensipar® and low dose vitamin D or escalating doses of vitamin D alone who are able to achieve the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) secondary hyperparathyroidism (HPT) treatment targets for both biointact parathyroid hormone (biPTH) and calcium-phosphorus (Ca x P) product.

Study Overview

• Status: Completed
• Conditions: Secondary Hyperparathyroidism
• Intervention / Treatment: Drug: Sensipar®; Drug: Vitamin D

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: - On hemodialysis for at least 3 months and have received intravenous vitamin D therapy (paricalcitol or doxercalciferol) for at least 3 months prior to entering screening - Historical iPTH 150-800 pg/ml (or biPTH 80-430 pg/ml) within 6 months and corrected serum Ca greater than 8.4 mg/dl within 2 months prior to screening period. For subjects with biPTH 80-160 pg/ml (iPTH 150-300 pg/ml), Ca x P must be greater than 55 mg²/dl² within 2 months prior to the screening period - Screening (pre-washout) biPTH 80-430 pg/ml and a corrected serum Ca level greater than 8.4 mg/dl. For subjects with biPTH 80-160 pg/ml Ca x P must be also greater than 55 mg²/dl² - Baseline mean biPTH (post-washout) greater than 160 pg/ml and mean corrected Ca greater than 8.4 mg/dl Exclusion Criteria: - Parathyroidectomy in the 3 month period prior to screening - Current gastrointestinal disorder that may be associated with impaired absorption of orally administered medications or an inability to swallow tablets - Use of investigational drug or device or participation in a trial of investigational drug or device within 30 days of screening - Females of child bearing potential who are pregnant (e.g., positive pregnancy test) or are breast feeding or who refuse to use highly effective contraceptive measures (as determined by the investigator) throughout the study - Previously participated in this or any other Sensipar® study or has received or is receiving Sensipar® as a commercially available product

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cinacalcet and low-dose Vitamin D; Cinacalcet and low-dose IV Vitamin D	Drug: Sensipar®; Cinacalcet hydrochloride; Other Names: Cinacalcet hydrochloride, Cinacalcet HCL, Cinacalcet; Drug: Vitamin D; Vitamin D administered IV; Other Names: paricalcitol, doxercalciferol
Active Comparator: Vitamin D alone; Escalating doses of IV Vitamin D alone	Drug: Vitamin D; Vitamin D administered IV; Other Names: paricalcitol, doxercalciferol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achieving the NKF-K/DOQI targets for both biPTH (80-160 pg/mL, equivalent to iPTH 150-300 pg/mL) and Ca x P (less than 55 mg^2/dL^2) during the assessment phase	Proportion of subjects in each treatment group simultaneously achieving the National Kidney Foundation - Kidney Disease Outcome Quality Initiative (NKF-K/DOQI) targets for both biPTH (80-160 pg/mL, equivalent to iPTH 150-300 pg/mL) and Ca x P (< 55 mg^2/dL^2) during the assessment phase (last 11 weeks of study following a 16-week titration phase)	Weeks 17 - 27

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change from Baseline for P During the Assessment Phase	Absolute change from baseline for serum phosphorus (P) during the assessment phase	Baseline to weeks 17-27
Proportion of Participants with ≥ 30% Reduction from Baseline in Mean iPTH During the Assessment Phase	Proportion of participants with ≥ 30% reduction from baseline in mean intact parathyroid hormone (iPTH) during the assessment phase.	Baseline and Weeks 17-27
Percent Change from Baseline for Calcium During the Assessment Phase	Percent Change from Baseline for Calcium (Ca) During the Assessment Phase	Baseline to weeks 17-27
Percent Change from Baseline for Phosphorus During the Assessment Phase	Percent change from baseline for Phosphorus (P) during the assessment phase	Baseline to weeks 17-27
Percent Change from Baseline for Ca x P During the Assessment Phase	Percent change from baseline for calcium x phosphorus (Ca x P) during the assessment phase	Baseline to weeks 17-27
Percent Change from Baseline for iPTH During the Assessment Phase	Percent change from baseline for intact parathyroid hormone (iPTH) during the assessment phase	Baseline to weeks 17-27
Proportion of Participants who Attained the K/DOQI Target Range for Ca x P During the Assessment Phase.	Proportion of participants who attained the K/DOQI target range for calcium x phosphorus (Ca x P) during the assessment phase.	Weeks 17 - 27
Proportion of Participants who Attained the K/DOQI Target Range for Ca During the Assessment Phase	Proportion of participants who attained the K/DOQI target range for calcium (Ca) during the assessment phase.	Weeks 17-27
Proportion of Participants who Attained the K/DOQI Target Range for iPTH During the Assessment Phase	Proportion of participants who attained the K/DOQI target range for intact parathyroid hormone (iPTH) during the assessment phase.	Weeks 17-27
Proportion of Participants who Attained the K/DOQI Target Range for P During the Assessment Phase.	Proportion of participants who attained the K/DOQI target range for phosphorus (P) during the assessment phase.	Weeks 17-27
Absolute Change from Baseline for iPTH During the Assessment Phase	Absolute change from baseline for intact parathyroid hormone (iPTH) during the assessment phase.	Baseline to weeks 17-27
Absolute Change from Baseline for Ca During the Assessment Phase	Absolute change from baseline for calcium (Ca) during the assessment phase	Baseline to weeks 17-27
Absolute Change from Baseline for Ca x P During the Assessment Phase	Absolute change from baseline for calcium x phosphorus (Ca x P) during the assessment phase.	Baseline to weeks 17-27

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Fishbane S, Shapiro WB, Corry DB, Vicks SL, Roppolo M, Rappaport K, Ling X, Goodman WG, Turner S, Charytan C. Cinacalcet HCl and concurrent low-dose vitamin D improves treatment of secondary hyperparathyroidism in dialysis patients compared with vitamin D alone: the ACHIEVE study results. Clin J Am Soc Nephrol. 2008 Nov;3(6):1718-25. doi: 10.2215/CJN.01040308.
• Shireman TI, Almehmi A, Wetmore JB, Lu J, Pregenzer M, Quarles LD. Economic analysis of cinacalcet in combination with low-dose vitamin D versus flexible-dose vitamin D in treating secondary hyperparathyroidism in hemodialysis patients. Am J Kidney Dis. 2010 Dec;56(6):1108-16. doi: 10.1053/j.ajkd.2010.07.012. Epub 2010 Oct 15.
• TBD.Sensipar plus low dose vitamin D (ACHIEVE).Journal-004521;
• TBD.Time in target.Journal-004521;

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Primary Completion (Actual): October 1, 2006
• Study Completion (Actual): December 1, 2006

Study Registration Dates

• First Submitted: August 24, 2005
• First Submitted That Met QC Criteria: August 25, 2005
• First Posted (Estimate): August 26, 2005

Study Record Updates

• Last Update Posted (Estimate): February 11, 2014
• Last Update Submitted That Met QC Criteria: February 7, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Vitamin D; Chronic Kidney Disease; Cinacalcet HCl; Sensipar®
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Parathyroid Diseases; Neoplastic Processes; Hyperparathyroidism; Neoplasm Metastasis; Hyperparathyroidism, Secondary; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Micronutrients; Hormone Antagonists; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Calcimimetic Agents; Vitamin D; Cinacalcet; 1 alpha-hydroxyergocalciferol
• Other Study ID Numbers: 20050102