Earlier Treatment of Kidney Disease Complication, Zemplar(reg) Shows Potential in Phase III Trial

Main Category: Urology / Nephrology
Article Date: 04 May 2005 - 14:00 PDT


Abbott today presented the results of its pivotal Phase III clinical studies for Zemplar(reg) (paricalcitol) Capsules in patients with stage three and four chronic kidney disease (CKD) who do not yet require dialysis. Study results indicate that Zemplar Capsules provided significant and sustained reduction in parathyroid hormone (PTH) levels in pre-dialysis stage three and four chronic kidney disease patients with secondary hyperparathyroidism (SHPT). The study compared Zemplar Capsules to placebo. Currently, many dialysis patients (stage five) with SHPT are treated with the injectable form of Zemplar.

The results were presented at the National Kidney Foundation 2005 Spring Clinical Meetings. SHPT is a major complication associated with CKD. If left untreated, it can detrimentally impact bones and other vital organs, including the heart, muscles and nerves. Reduction in PTH level is a key indicator for SHPT treatment efficacy.

According to the National Kidney Foundation, more than 20 million Americans - one in nine adults - have CKD and an additional 20 million are at risk, creating what the National Institutes of Health describes as a "growing epidemic." Zemplar Capsules are an investigational oral therapy developed for the treatment of SHPT associated with CKD.

"The research findings for Zemplar Capsules represent new hope for millions of chronic kidney disease patients. The Phase III studies demonstrate substantial parathyroid hormone reduction, with encouraging adverse event results that make it possible to treat SHPT earlier in the CKD continuum," said Daniel W. Coyne, M.D., associate professor of medicine at Washington University School of Medicine and lead investigator for the Zemplar Capsules Phase III studies. "Previously, limitations with treatment options prevented widespread intervention for secondary hyperparathyroidism in pre-dialysis patients."

Results from Zemplar Capsules Phase III Clinical Studies

Study results from three Phase III trials showed that Zemplar Capsules were safe and effective in reducing parathyroid hormone (PTH) levels in stage three and four kidney disease patients with SHPT. Ninety-one percent of patients treated with Zemplar Capsules had significant and sustained reduction in PTH levels, compared to only 13 percent of placebo patients, after 24 weeks of therapy. Significant reduction in PTH was defined as achievement of at least two consecutive, greater than or equal to 30 percent reductions in PTH. Additionally, patients had a greater than 30 percent mean reduction in PTH by week nine, with a sustained reduction in PTH noted throughout the remainder of the study.

Zemplar Capsule treatment had minimal impact on calcium and phosphorus levels when compared to placebo. Elevations in blood calcium, phosphorus and urinary calcium values are known treatment-related safety concerns that have been associated with treatment of SHPT in stage three and four CKD patients with activated vitamin D therapy. The incidence of clinically meaningful hypercalcemia (2 percent paricalcitol vs. 0 percent placebo) or elevations in phosphorus (10 percent paricalcitol vs. 12 percent placebo) were not significantly different between Zemplar Capsules and placebo. Additionally, there was no significant difference in the change in urinary calcium excretion from baseline to endpoint between Zemplar Capsules and placebo.

Results from the Phase III pivotal trials showed no statistically significant difference in adverse events in patients treated with Zemplar Capsules when compared to placebo. The only adverse event reported by significantly more patients than placebo, regardless of causality, was vertigo (5 percent paricalcitol vs. 0 percent placebo).

Phase III clinical trials for Zemplar Capsules included patients in stages three (moderate) and four (severe) of chronic kidney disease, who were treated and evaluated in three prospective, randomized, placebo-controlled, double-blinded studies at multiple centers over a 24-week period. Additionally, this trial represents the largest number of patients studied in the early-stage CKD population with SHPT.

Results from National Kidney Foundation Guidelines Achievement Study with Zemplar Capsules

The Phase III trial data were further analyzed to evaluate consistency with the National Kidney Foundation in the Kidney Disease Outcomes Quality Initiative K/DOQI guidelines for calcium (Ca) and phosphorus (P) targets. Maintaining appropriate levels of Ca and P is critical for the effective management of SHPT.

Results showed that Zemplar Capsules allow for reduction and suppression of PTH consistent with the overall Phase III study findings. Additionally, Ca, P, and calcium and phosphorus product (Ca X P) values were maintained within the K/DOQI targets for: calcium (91 percent paricalcitol vs. 95 percent placebo), phosphorus (70 percent paricalcitol vs. 75 percent placebo) and calcium and phosphorus combined (94 percent paricalcitol vs. 96 percent placebo).

Zemplar Capsules Background

Zemplar Capsules are an investigational oral form of activated vitamin D that has been developed for the treatment of SHPT in stage three and four CKD patients. Zemplar Injection was introduced in 1998 and has become the most widely-used activated vitamin D therapy for the prevention and treatment of SHPT among dialysis patients. In July 2004, Abbott submitted a New Drug Application (NDA) with the Food and Drug Administration for Zemplar Capsules to treat CKD stage three and four patients who do not require dialysis.

"Zemplar Capsules Phase III study results represent an important milestone for patients with chronic kidney disease and demonstrates Abbott's continued commitment to the renal and primary care community," said Laura A. Williams, M.D., M.P.H., global project head, Renal Global Project Team, Abbott.

About Kidney Disease And Secondary Hyperparathyroidism

According to the National Kidney Foundation, more than 20 million Americans - one in nine adults - have CKD and an additional 20 million are at risk, creating what the National Institutes of Health describes as a "growing epidemic." Two major risk factors for kidney disease are diabetes and hypertension, which account for two-thirds of new cases each year. Minority populations also bear a disproportionate burden. CKD includes five stages. Stage five requires the need for dialysis or kidney transplant.

When kidneys start to fail, they gradually lose their ability to activate the vitamin D they obtain through diet and other sources. As a result, many kidney patients develop SHPT, a serious disorder that causes bone disease and can affect many organs and tissues, including red blood cells, the heart, nerves and muscles. If SHPT is not managed early it can worsen, leading to other related conditions and progression of the underlying kidney disease.

Indication and Important Safety Information - Zemplar (paricalcitol) Injection

Zemplar Injection is indicated for the prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure or stage five CKD.

Adverse effects with greater than 5 percent frequency with Zemplar Injectable versus placebo, regardless of causality, were nausea (13 percent vs. 8 percent), vomiting (8 percent vs. 4 percent), and edema (7 percent vs. 0 percent). Zemplar is contraindicated in patients with vitamin D toxicity, hypercalcemia, or hypersensitivity to product ingredients. Administration may place patients at risk for hypercalcemia, elevated Ca x P product, and metastatic calcification. For full prescribing information on Zemplar Injection visit http://www.zemplar.com.

About Abbott

Abbott is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs more than 60,000 people and markets its products in more than 130 countries.

http://www.abbott.com/news/press

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