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

NCT00860093 | Terminated Phase 2 DMC

• 1 other identifier: MPC-5971
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Nephrolithiasis

Keywords

Kidney Calculi; Urolithiasis; Lithotripsy; potassium compounds; magnesium compounds

Outcome Measures

Primary Outcomes (1)

• stone free rate after SWL treatment

  12 weeks

Secondary Outcomes (3)

• increase in urine inhibitors

  4 week and 12 week

• Reduced need for secondary procedures such as URS to clear obstructive fragments

  12 weeks

• reduced stone/fragment area (mm2),percent change from the treatment stone area (mm2)

  12 weeks

Study Arms (2)

1

EXPERIMENTAL

MPC-5971

Drug: MPC-5971

2

PLACEBO COMPARATOR

placebo identical in appearance to study drug

Other: placebo

Interventions

placebo OTHER

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.

2

MPC-5971 DRUG

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.

1

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mission Pharmacal: lead

Study Sites (3)

Idaho Urologic Institute

Meridian, Idaho, 83642, United States

Location

Columbus Urology Research

Columbus, Ohio, 43220, United States

Location

Urology Clinics of North Texas, PA

Dallas, Texas, 75231, United States

Location

Related Publications (13)

• 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. doi: 10.1016/s0022-5347(17)38330-1.

  PMID: 1988724 BACKGROUND

• 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. doi: 10.1002/jbmr.5650070306.

  PMID: 1585829 BACKGROUND

• 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. doi: 10.1016/s0022-5347(01)68155-2.

  PMID: 9366314 BACKGROUND

• 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. doi: 10.1046/j.1365-2036.1998.00280.x.

  PMID: 9692708 BACKGROUND

• 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. doi: 10.1177/009127009803801108.

  PMID: 9824785 BACKGROUND

• 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. doi: 10.1097/00045391-199901000-00007.

  PMID: 10423646 BACKGROUND

• 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. doi: 10.1016/s0272-6386(99)70115-0.

  PMID: 10401023 BACKGROUND

• 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. doi: 10.1046/j.1523-1755.2000.00881.x.

  PMID: 10652038 BACKGROUND

• 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.

  PMID: 15117041 BACKGROUND

• 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. doi: 10.1111/j.1442-2042.2005.01001.x.

  PMID: 15733107 BACKGROUND

• 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.

  PMID: 15822549 BACKGROUND

• 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. doi: 10.1097/01.mjt.0000149922.16098.c0.

  PMID: 16645424 BACKGROUND

• 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. doi: 10.1016/j.juro.2007.01.156.

  PMID: 17509313 BACKGROUND

MeSH Terms

Conditions

Nephrolithiasis; Kidney Calculi; Urolithiasis

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Calculi; Calculi; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2009
• First Posted: March 11, 2009
• Study Start: April 1, 2010
• Primary Completion: November 1, 2010
• Study Completion: December 1, 2010
• Last Updated: March 7, 2019

Record last verified: 2019-03

Locations

US (3)