A Dose Escalation Study of VS-505 in End Stage Renal Disease Patients Undergoing Hemodialysis

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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A Dose Escalation Study of VS-505 to Evaluate the Tolerability, Safety and Efficacy in End Stage Renal Disease Patients Undergoing Hemodialysis

Conditions
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End Stage Renal Disease, Hyperphosphatemia

Intervention / Treatment
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* Dietary Supplement: VS-505


Participation Criteria
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Eligibility Criteria
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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 Injectable iron agents Oral or injectable active vitamin D3 Oral nutritional vitamin D Calcimimetics Calcium supplements Anti-osteoporotic medication including bisphosphonates 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VS-505<br>750 mg capsule | Dietary Supplement: VS-505<br>* VS-505 is orally administered with meal for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inorganic phosphorus (Pi) change from baseline to end of treatment |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calcium (Ca) change from baseline to end of treatment |  | 8 weeks | 
| Ca x Pi change from baseline to end of treatment |  | 8 weeks | 
| intact parathyroid hormone change from baseline to end of treatment |  | 8 weeks | 
| Rate of patients whose Pi reduction is 0.65 mmol/L (2.0 mg/dL) |  | 8 weeks | 
| Rate of patients whose Pi reaches the goal between 1.13 mmol/L (3.5 mg/dL) and 1.94 mmol/L (6.0 mg/dL) |  | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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phosphate binder, dialysis