An Extension Study Designed to Assess Effects of Losartan on Proteinuria in Pediatric Populations (MK-0954-326 AM1,EXT1(AM2))

NCT00568178 | Completed Phase 3 Results

• 2 other identifiers: 0954-3262006-006415-74
• Study Type: interventional
• Target: 306
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the effects of losartan on proteinuria in pediatric patients.

Conditions

Proteinuria

Outcome Measures

Primary Outcomes (3)

• Double-Blind Treatment Phase: Percent Change From Baseline in Urinary Protein/Creatinine (Pr/Cr) Ratio (gm/gm) at Week 12

  Change in urinary protein excretion, determined as urinary Pr/Cr ratio compared to baseline\*, after approximately twelve weeks of treatment. Baseline is defined as values obtained at Visit 3, Week (-1) during the Single Blind Run-in period.

  Baseline and Week 12

• Open Label Extension: Percent Change From Baseline of Urinary Pr/Cr Ratio (gm/gm) at Month 36

  Change in urinary protein excretion, determined as urinary Pr/Cr ratio compared to baseline\*, after approximately three years of treatment. \*The baseline for efficacy data in the extension was defined as the last value obtained in the double-blind treatment phase.

  Baseline and Month 36

• Open Label Extension: Change From Baseline in Glomerular Filtration Rate (GFR) at Month 36

  The outcome measure of glomerular filtration rate was based on mL/min/1.73m\^2, as determined by the Schwartz formula: GFR = \_\_\_\_\_0.55 x height (cm)\_\_\_\_\_\_\_ divided by serum creatinine (mg/dL) GFR values were compared to the baseline GFR measure. \[Note: For male participants, ages 13 to 17 years, 0.70 was used as the multiplier in place of 0.55\] Baseline in regard to the extension is defined as the last value obtained in the double-blind treatment phase.

  Baseline and Month 36

Secondary Outcomes (2)

• Double-Blind Treatment Phase: Change From Baseline in Systolic Blood Pressure in Hypertensive Participants at Week 12

  Baseline and Week 12

• Double-Blind Treatment Phase: Change From Baseline in Diastolic Blood Pressure in Hypertensive Participants at Week 12

  Baseline and Week 12

Study Arms (4)

Losartan Double-Blind Base Study (12-weeks)

EXPERIMENTAL

Normotensive participants received losartan. Hypertensive participants received either active losartan (plus amlodipine placebo) OR active amlodipine (plus losartan placebo).

Drug: Losartan Potassium; Other: Comparator: Placebo (Losartan)

Amlodipine Double-Blind Base Study (12-weeks)

ACTIVE COMPARATOR

Hypertensive participants were randomized to receive either active losartan (plus amlodipine placebo) OR active amlodipine (plus losartan placebo) for 12 weeks.

Other: Comparator: Placebo (Losartan); Drug: Comparator: amlodipine besylate; Other: Comparator: Placebo (amlodipine besylate); Other: Placebo (Losartan)

Losartan Open-Label Extension Phase (Month 36)

EXPERIMENTAL

Participants were were carried over from the base study into the long-term safety extension. Participants in the extension were randomly assigned to either losartan or enalapril regardless of their previous randomized treatment. Dosing during the extension period (i.e. starting dose and any titration) was up to the investigator and varied by patient).

Drug: Losartan Potassium

Enalapril Open-Label Extension Phase (Month 36)

ACTIVE COMPARATOR

Participants were were carried over from the base study into the long-term safety extension. Participants in the extension were randomly assigned to either losartan or enalapril regardless of their previous randomized treatment. Dosing during the extension period (i.e. starting dose and any titration) was up to the investigator and varied by patient).

Drug: Enalapril Maleate

Interventions

Losartan Potassium DRUG

Losartan Use During the Double-Blind Treatment Phase: Losartan potassium was administered orally as tablets; 25 or 50 milligrams (mg); or as a liquid suspension 2.5 mg/mL prepared for participants who weighed less than 25 kilograms (kg) or for those participants unable to swallow tablets. During the double-blind period, participants were initially randomized to either a once-daily weight-dependent dose of approximately 0.7 mg/kg (25 mg tablet; up to 50 mg per day) and at 2-weeks the dose was increased to a once-daily maximum weight-dependent dose of 1.4 mg/kg. The maximum dose of losartan, as specified in the protocol, was 50 mg/day (if the patient weighed \<50 kg) or 100 mg/day (if the patient weighed ≥50 kg). Losartan Use During the Treatment Extension Phase: Dose modifications of the drug were left up to the discretion of the Investigators based on each participant's level of tolerance.

Also known as: Cozaar®

Losartan Double-Blind Base Study (12-weeks); Losartan Open-Label Extension Phase (Month 36)

Comparator: Placebo (Losartan) OTHER

Placebo (losartan suspension), administered orally, once daily for 12 weeks

Amlodipine Double-Blind Base Study (12-weeks); Losartan Double-Blind Base Study (12-weeks)

Comparator: amlodipine besylate DRUG

Amlodipine besylate (1 mg/mL) liquid suspension, oral administration, titrated to 0.2 mg/kg/day (5 mg maximum dose) per day for 12 Weeks

Also known as: NORVASC®

Amlodipine Double-Blind Base Study (12-weeks)

Comparator: Placebo (amlodipine besylate) OTHER

Liquid suspension, 1mg/mL, titrated to 0.2 mg/kg/day (5 mg maximum dose) once daily, for 12 weeks

Also known as: NORVASC®

Amlodipine Double-Blind Base Study (12-weeks)

Placebo (Losartan) OTHER

Normotensive patients randomized to losartan placebo for 12 weeks.

Amlodipine Double-Blind Base Study (12-weeks)

Enalapril Maleate DRUG

Enalapril 2.5-, 5-, 10-, and 20-mg tablets or enalapril suspension (1 mg/mL), oral administration, once daily for 36 months.

Also known as: Vasotec®, Renitec®

Enalapril Open-Label Extension Phase (Month 36)

Eligibility Criteria

• Age: 12 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participant is 1 to 17 years of age
• Able to provide a first-morning urine sample each day during the study
• Documented history of proteinuria associated with chronic kidney disease of any origin
• Signed consent of parent and/or legal guardian

You may not qualify if:

• Pregnant and/or nursing
• Requires more than 2 medications to control high blood pressure
• Has undergone major organ transplantation (e.g. heart, kidney, liver)
• Known sensitivity to losartan or other similar drugs, or any history of angioneurotic edema
• Known sensitivity to amlodipine or other calcium channel blocker
• Requires cyclosporine to treat renal disease (kidney disease)

Sponsors & Collaborators

• Organon and Co: lead

Related Publications (3)

• Webb NJ, Shahinfar S, Wells TG, Massaad R, Gleim GW, McCrary Sisk C, Lam C. Losartan and enalapril are comparable in reducing proteinuria in children with Alport syndrome. Pediatr Nephrol. 2013 May;28(5):737-43. doi: 10.1007/s00467-012-2372-9. Epub 2012 Dec 4.

  PMID: 23207876 DERIVED

• Webb NJ, Shahinfar S, Wells TG, Massaad R, Gleim GW, Santoro EP, Sisk CM, Lam C. Losartan and enalapril are comparable in reducing proteinuria in children. Kidney Int. 2012 Oct;82(7):819-26. doi: 10.1038/ki.2012.210. Epub 2012 Jun 27.

  PMID: 22739977 DERIVED

• Webb NJ, Lam C, Shahinfar S, Strehlau J, Wells TG, Gleim GW, Le Bailly De Tilleghem C. Efficacy and safety of losartan in children with Alport syndrome--results from a subgroup analysis of a prospective, randomized, placebo- or amlodipine-controlled trial. Nephrol Dial Transplant. 2011 Aug;26(8):2521-6. doi: 10.1093/ndt/gfq797. Epub 2011 Feb 1.

  PMID: 21285125 DERIVED

MeSH Terms

Conditions

Proteinuria

Interventions

Losartan; Amlodipine; Enalapril; Enalaprilat

Condition Hierarchy (Ancestors)

Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles; Dihydropyridines; Pyridines; Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2007
• First Posted: December 5, 2007
• Study Start: June 1, 2007
• Primary Completion: September 1, 2008
• Study Completion: March 1, 2011
• Last Updated: May 23, 2024
• Results First Posted: October 30, 2009

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share