a dose escalation study of vs-505 in end stage renal disease patients undergoing hemodialysis

Conditions: End Stage Renal Disease; Hyperphosphatemia

Summary: the purpose is to evaluate the tolerability, safety and efficacy of vs-505 when given with meal for 8 weeks to hemodialysis patients with hyperphosphatemia

this study consists of 4 period; 1) screening period: up to 30 days, 2) first washout period: 2 weeks (remove existing phosphate binder effect), 3) treatment period: 8 weeks, and 4) second washout period: 2 weeks (remove vs-505 effect). vs-505 is orally administered with meal for 8 weeks. the starting dose of vs-505 is 1.50 g/day and the dose will be elevated step wise from 1.50 g to 2.25 g, 4.50 g and 6.75 g per day based on the safety assessment and plasma pi level every 2 weeks during the treatment period.

Eligibility criteria:
inclusion criteria: * written informed consent given * able to comply with the study procedures and medications * on a stable hemodialysis (hd) regimen (3 times per week) including hemodialysis and hemodiafiltration for ≥12 weeks at screening and during the study period * no change in prescribed dose or frequency of any of the following medications within 4 weeks prior to screening 1. injectable iron agents 2. oral or injectable active vitamin d3 3. oral nutritional vitamin d 4. calcimimetics 5. calcium supplements 6. anti-osteoporotic medication including bisphosphonates 7. calcitonins * must be willing to avoid intentional changes in diet throughout the study * women of child-bearing potential or non-sterile male subjects and those who are sexually active with a non-sterile female partner must agree to use highly effective contraception * plasma pi level \>1.94 mmol/l (6.0 mg/dl) to \<3.23 mmol/l (10.0 mg/dl) after 2 weeks washout will qualify patients to enter the treatment period exclusion criteria: * blood purification therapy other than hd (hemodialysis and hemodiafiltration) * the plasma pi level is \>2.26 mmol/l (7.0 mg/dl) within the latest three tests prior to screening. * variation of the plasma pi is over 0.65 mmol/l (2.0 mg/dl) within the latest three tests prior to screening. * pre-emptive or scheduled renal transplant * history of hemochromatosis or ferritin ≥1000 mcg/l * oral iron agents including prescribed and over-the-counter drugs at screening. * current clinically significant gastrointestinal (gi) disorder, including gi bleeding, colitis, inflammatory bowel disease, irritable bowel syndrome, chronic constipation, new diagnosis of peptic or duodenal ulcer disease, within 4 weeks prior to screening * history of gastrectomy or duodenectomy, or gi tract surgery within 12 weeks prior to screening * hypertension: defined using pre-dialysis vital of diastolic blood pressure \>110 mmhg or systolic blood pressure \>180 mmhg * possible parathyroid intervention including surgical parathyroidectomy and percutaneous ethanol injection therapy during the study period * clinical evidence of active malignancy and/or receiving systemic chemotherapy/radiotherapy with the exception of basal cell or squamous carcinoma of the skin * severe cardiovascular disorders such as recent myocardial infarction; unstable angina; congested heart failure (nyha class ii or above) hospitalized within 24 weeks (6 months), valve stenosis, atrial fibrillation and arrhythmia * history of event by cerebrovascular disease or cardiovascular disease within 24 weeks (6 months) prior to screening * active infection or current treatment with antibiotics within 2 weeks prior to screening * history of hiv (elisa and western blot) test results * known active liver disease with aspartate aminotransferase or alanine aminotransferase levels greater than x3 the upper limit of normal * hepatitis b and/or hepatitis c treated with antiviral treatment within 4 weeks prior to screening * history of allergy of vs-505 and its related components * receipt of any investigational drug within 4 weeks prior to screening * pregnant and breast-feeding women * other patients who in the opinion of the investigators are ineligible for the study

Keywords: phosphate binder dialysis