Efficacy and Safety of Using MPC-5971 in Subjects Undergoing Shock Wave Lithotripsy

A Multi-Site Placebo-Controlled Randomized Double-Blind Study to Evaluate the Efficacy and Safety of Using MPC-5971 as Adjuvant Therapy in Subjects Undergoing Shock Wave Lithotripsy

The purpose of this study is to evaluate the efficacy of MP-5971 in facilitating stone passage after Shock Wave Lithotripsy treatment.

Shock Wave Lithotripsy (SWL) is widely utilized as a first line therapy in patients with renal calculi. SWL is associated with limited morbidity, however, complications relating to stone fragment passage after treatment can occur, the most serious being ureter obstruction. In addition, the growth and agglomeration of residual fragments after SWL treatment, in approximately 40% of patients, will lead to another stone episode within 12 months. Adjunct therapy with MPC-5971 should reduce the risk of complications of residual stone fragments by facilitating passage, preventing blockage and inhibiting growth and enlargement of residual fragments. This is based on MPC-5971's ability to increase urinary inhibitors against growth and agglomeration of stone fragments and by reducing urinary saturation of calcium oxalate and uric acid. The objective is to see a decrease in fragment complications and a significant increase in the stone free rate at 3 months following SWL treatment in combination with MPC-5971.

Inclusion criteria:

• Male or female subject aged > or equal to 18 to < or equal to 70.
• Subject has undergone a computerized tomography (CT) scan within 30 days of the screening visit.
• Subject has been diagnosed with single unilateral renal calculus (target treatment stone).
• Target treatment stone, is presumed to be of calcium composition and/or uric acid composition.
• Target treatment stone is between > or equal to 5 and < or equal to 15 mm in diameter.
• Contra lateral kidney may hold a clinically inconsequential size calculus that does not require concurrent SWL treatment.
• Both kidneys are anatomically normal.
• An appropriate candidate for SWL, determined by treating physician.
• Female subjects with a negative pregnancy test, hysterectomy, tubal ligation or non-child bearing potential (post-menopausal).
• Female subjects of child bearing potential with a negative pregnancy test and taking appropriate birth control for the duration of the study.
• Urine is pyuria negative and nitrite negative on dipstick and/or negative upon microscopic evaluation.
• Subject must voluntarily consent to participate in this study and provide his/her written informed consent prior to start of any study-specific procedures.

Exclusion Criteria:

• Current or past history of cystine stones or infection stones.
• Renal insufficiency, defined as serum creatinine value outside of the normal reference range.
• Currently has or had hyperkalemia within the past six months, defined as serum potassium outside of the normal reference range.
• Currently has or had hypermagnesemia within the past six months, defined as serum magnesium outside of the normal reference range.
• Active urinary tract infection.
• Renal calculi in an anatomically abnormal kidney; horseshoe shape, ureteropelvic junction obstruction or calyceal diverticulum.
• Altered urinary tract anatomy such as a transplant kidney, urinary reconstruction or congenital anomaly.
• Blood coagulopathies and or taking anticoagulants (warfarin, coumarin, heparin).
• Taking salicylate (aspirin), including low dose aspirin for cardio-prophylaxis or other NSAID (OTC) that may increase bleeding time, within the past 7 days.
• History of complications with previous SWL; pyelonephritis, perinephric hematoma.
• Unsuccessful SWL treatments for previous stone within the past six months.
• Currently has or previously had ulcers of the esophagus, stomach and/or small intestines.
• Chronic diarrhea or has a history of diarrhea.
• Bowel disease such as Crohn's disease, Celiac disease, fat malabsorption or Sprue.
• Undergone any bariatric surgery procedures.
• Obese, defined as BMI >30.
• Uncontrolled hypertension defined as subjects taking medication specific for hypertension or subject not on medication with systolic blood pressure above 140 and diastolic above 90.
• Adrenal insufficiency (i.e., Addison's disease), adrenal tumors, and/or subjects on adrenal hormone replacement therapy.
• Taking potassium-sparing diuretics (triamterene, amiloride, spironolactone, Midamor®, Aldactone®, Dyrenium®, Eplerenone®).
• Taking potassium supplements (Rx or OTC) within the past 15 days.
• Taking magnesium supplements (Rx or OTC) within the past 15 days.
• Taken potassium citrate supplements (Rx or OTC) within the past 30 days.
• Subject taking anticholinergic medications at entry (dicyclomine, atropine, scopolamine, oxybutynin, tolerodine, Cogentin®, Sinemet®, Robinal®, Kenadrin®, Artane®, Enablex®, Detrol®, Vesicare®, Sanctura®, Ditropan®, Oxytrol®, Bentyl®, Byclomine®, Dibent®, Di-Spaz®, or Dilomine®). (Subjects may be prescribed anticholinergics as standard of care with use of stents post entry.)
• Subject is has taken gastrointestinal enzyme replacement therapy or proton pump inhibitors within past 30 days (Ultrase®, Creon®, Viokase®, Pancrease® MT, pancrelipase agents, Aciphex®, Nexium®, Prevacid®, Protonix®, Zegerid® Prilosec OTC®, Kapidex®, rabeprazole, esomeprazole, lansoprazole, pantoprazole, omeprazole, dexlansoprazole).
• Women who are pregnant or lactating.
• Subjects with a known hypersensitivity to potassium, magnesium, citrate or any excipients in the drug formulation