The FDA ( Food and Drug Administration ) has approved Zemplar ( Paricalcitol ) capsules, an oral, activated vitamin D therapy for prevention and treatment of secondary hyperparathyroidism ( SHPT ).
Zemplar capsules are indicated for the prevention and treatment of SHPT in stages three and four chronic kidney disease ( CKD ) patients, before the need for dialysis or transplantation.
SHPT is a major complication associated with CKD that can detrimentally impact bones and other vital organs, including the heart, muscles and nerves if left untreated.
It can occur when kidneys lose their ability to activate vitamin D obtained through diet and other sources.
One in nine adults in the U.S., or 20 million people have CKD and another 20 million are at risk for developing CKD from underlying causes such as diabetes and hypertension.
" Until now, physicians have had limited treatment options to manage secondary hyperparathyroidism in earlier-stage CKD patients. Zemplar capsules represent the opportunity to treat this population with a convenient, safe and effective activated vitamin D therapy," said Daniel W. Coyne, at Washington University School of Medicine and lead investigator for the Zemplar capsules Phase III studies.
Zemplar capsules are a new, oral formulation of Zemplar injection, which was introduced in 1998 and is the most widely-used activated vitamin D for the prevention and treatment of SHPT among dialysis patients.
Zemplar capsules were designed to reduce parathyroid hormone levels ( PTH ) with minimal impact on calcium and phosphorus levels in a convenient oral form.
Reduction of PTH is a key indicator of treatment efficacy.
Clinical trial results show that Zemplar capsules had minimal impact on calcium and phosphorus levels when compared to placebo.
The National Kidney Foundation guidelines recommend testing for and treating SHPT early in CKD, well before the need for dialysis. Earlier management of CKD and its complications may reduce the devastating consequences of the disease, such as bone loss and cardiovascular events.
Study results from three Phase III trials showed that Zemplar capsules are 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.
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 and phosphorus targets.
Calcium, phosphorus 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 ).
Maintaining appropriate levels of calcium and phosphorus is critical for the effective management of SHPT.
Bone disease is a known complication of SHPT that occurs as the kidneys gradually lose their ability to produce activated vitamin D, which is necessary for bone health.
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.
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.
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.
The safety profile of Zemplar was similar to placebo. Zemplar is contraindicated in patients with vitamin D toxicity, hypercalcemia, or hypersensitivity to any product ingredient.
PTH, calcium and phosphorus levels should be monitored every three months and more frequently during dosage changes.
Dosage titration is required to reach optimum reduction/levels of PTH.
Excessive administration of vitamin D compounds, including Zemplar capsules, can cause oversuppresion of PTH, hypercalcemia, hypercalciuria, hyperphosphatemia and adynamic bone disease.
Source: Abbott, 2005