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

Nephrolithiasis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00860093
• Other study ID #: MPC-5971
• Status: Terminated
• Phase: Phase 2
• Start date: April 2010
• Est. completion date: December 2010

Study information

• Verified date: March 2019
• Source: Mission Pharmacal
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 135
• Est. completion date: December 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Kidney Calculi
• Nephrolithiasis

Intervention

Other:
• placebo
After SWL treatment subjects will be randomized to receive either MPC-5971 or placebo. Two tablets of MPC-5971 or placebo will be taken orally twice a day (bid). This will give a daily dosage equal to 40 mEq of potassium, 20 mEq of magnesium and 60 mEq of citrate. MPC-5971 or placebo will be taken bid for 90 days beginning immediately after SWL treatment.

Drug:
• MPC-5971
After SWL treatment subjects will be randomized to receive either MPC-5971 or placebo. Two tablets of MPC-5971 or placebo will be taken orally twice a day (bid). This will give a daily dosage equal to 40 mEq of potassium, 20 mEq of magnesium and 60 mEq of citrate. MPC-5971 or placebo will be taken bid for 90 days beginning immediately after SWL treatment.

Locations

Country	Name	City	State
United States	Columbus Urology Research	Columbus	Ohio
United States	Urology Clinics of North Texas, PA	Dallas	Texas
United States	Idaho Urologic Institute	Meridian	Idaho

Sponsors (1)

Lead Sponsor	Collaborator
Mission Pharmacal

Country where clinical trial is conducted

United States, 

References & Publications (13)

Ettinger B, Pak CY, Citron JT, Thomas C, Adams-Huet B, Vangessel A. Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis. J Urol. 1997 Dec;158(6):2069-73. — View Citation

Gonzalez GB, Pak CY, Adams-Huet B, Taylor R, Bilhartz LE. Effect of potassium-magnesium citrate on upper gastrointestinal mucosa. Aliment Pharmacol Ther. 1998 Jan;12(1):105-10. — View Citation

Jaipakdee S, Prasongwatana V, Premgamone A, Reungjui S, Tosukhowong P, Tungsanga K, Suwantrai S, Noppawinyoowong C, Maskasame S, Sriboonlue P. The effects of potassium and magnesium supplementations on urinary risk factors of renal stone patients. J Med Assoc Thai. 2004 Mar;87(3):255-63. — View Citation

Koenig K, Padalino P, Alexandrides G, Pak CY. Bioavailability of potassium and magnesium, and citraturic response from potassium-magnesium citrate. J Urol. 1991 Feb;145(2):330-4. — View Citation

Odvina CV, Mason RP, Pak CY. Prevention of thiazide-induced hypokalemia without magnesium depletion by potassium-magnesium-citrate. Am J Ther. 2006 Mar-Apr;13(2):101-8. — View Citation

Pak CY, Koenig K, Khan R, Haynes S, Padalino P. Physicochemical action of potassium-magnesium citrate in nephrolithiasis. J Bone Miner Res. 1992 Mar;7(3):281-5. — View Citation

Ruml LA, Gonzalez G, Taylor R, Wuermser LA, Pak CY. Effect of varying doses of potassium-magnesium citrate on thiazide-induced hypokalemia and magnesium loss. Am J Ther. 1999 Jan;6(1):45-50. — View Citation

Ruml LA, Pak CY. Effect of potassium magnesium citrate on thiazide-induced hypokalemia and magnesium loss. Am J Kidney Dis. 1999 Jul;34(1):107-13. — View Citation

Ruml LA, Wuermser LA, Poindexter J, Pak CY. The effect of varying molar ratios of potassium-magnesium citrate on thiazide-induced hypokalemia and magnesium loss. J Clin Pharmacol. 1998 Nov;38(11):1035-41. — View Citation

Sriboonlue P, Jaipakdee S, Jirakulsomchok D, Mairiang E, Tosukhowong P, Prasongwatana V, Savok S. Changes in erythrocyte contents of potassium, sodium and magnesium and Na, K-pump activity after the administration of potassium and magnesium salts. J Med Assoc Thai. 2004 Dec;87(12):1506-12. — View Citation

Tosukhowong P, Tungsanga K, Phongudom S, Sriboonlue P. Effects of potassium-magnesium citrate supplementation on cytosolic ATP citrate lyase and mitochondrial aconitase activity in leukocytes: a window on renal citrate metabolism. Int J Urol. 2005 Feb;12(2):140-4. — View Citation

Wuermser LA, Reilly C, Poindexter JR, Sakhaee K, Pak CY. Potassium-magnesium citrate versus potassium chloride in thiazide-induced hypokalemia. Kidney Int. 2000 Feb;57(2):607-12. — View Citation

Zerwekh JE, Odvina CV, Wuermser LA, Pak CY. Reduction of renal stone risk by potassium-magnesium citrate during 5 weeks of bed rest. J Urol. 2007 Jun;177(6):2179-84. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	stone free rate after SWL treatment		12 weeks
Secondary	increase in urine inhibitors		4 week and 12 week
Secondary	Reduced need for secondary procedures such as URS to clear obstructive fragments		12 weeks
Secondary	reduced stone/fragment area (mm2),percent change from the treatment stone area (mm2)		12 weeks