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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00568178
First received: December 3, 2007
Last updated: March 16, 2012
Last verified: March 2012
  Purpose

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


Condition Intervention Phase
Proteinuria
Drug: Losartan Potassium
Other: Comparator: Placebo (Losartan)
Drug: Comparator: amlodipine besylate
Other: Comparator: Placebo (amlodipine besylate)
Other: Placebo (Losartan)
Drug: Enalapril Maleate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Parallel, Placebo or Amlodipine-Controlled Study of the Effects of Losartan on Proteinuria in Pediatric Patients With or Without Hypertension

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Double-Blind Treatment Phase: Percent Change From Baseline in Urinary Protein/Creatinine (Pr/Cr) Ratio (gm/gm) at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

    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.


  • Open Label Extension: Percent Change From Baseline of Urinary Pr/Cr Ratio (gm/gm) at Month 36 [ Time Frame: Baseline and Month 36 ] [ Designated as safety issue: No ]

    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.


  • Open Label Extension: Change From Baseline in Glomerular Filtration Rate (GFR) at Month 36 [ Time Frame: Baseline and Month 36 ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Double-Blind Treatment Phase: Change From Baseline in Systolic Blood Pressure in Hypertensive Participants at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Double-Blind Treatment Phase: Change From Baseline in Diastolic Blood Pressure in Hypertensive Participants at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

Enrollment: 306
Study Start Date: June 2007
Study Completion Date: March 2011
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Losartan Double-Blind Base Study (12-weeks)
Normotensive participants received losartan. Hypertensive participants received either active losartan (plus amlodipine placebo) OR active amlodipine (plus losartan placebo).
Drug: Losartan Potassium

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.

Other Name: Cozaar®
Other: Comparator: Placebo (Losartan)
Placebo (losartan suspension), administered orally, once daily for 12 weeks
Active Comparator: Amlodipine Double-Blind Base Study (12-weeks)
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)
Placebo (losartan suspension), administered orally, once daily for 12 weeks
Drug: Comparator: amlodipine besylate
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
Other Name: NORVASC®
Other: Comparator: Placebo (amlodipine besylate)
Liquid suspension, 1mg/mL, titrated to 0.2 mg/kg/day (5 mg maximum dose) once daily, for 12 weeks
Other Name: NORVASC®
Other: Placebo (Losartan)
Normotensive patients randomized to losartan placebo for 12 weeks.
Experimental: Losartan Open-Label Extension Phase (Month 36)
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

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.

Other Name: Cozaar®
Active Comparator: Enalapril Open-Label Extension Phase (Month 36)
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
Enalapril 2.5-, 5-, 10-, and 20-mg tablets or enalapril suspension (1 mg/mL), oral administration, once daily for 36 months.
Other Names:
  • Vasotec®
  • Renitec®

Detailed Description:

The study included a 12-week double-blind treatment phase and a 36-month open-label extension phase. Participants who completed or discontinued the initial 12-week phase of the study and who opted to participate in the open label extension phase were randomized to either losartan or enalapril at a dose of the investigator's choosing for the duration of the extension. The open label extension was designed to continue until the 100th participant completed 3 years of follow-up.

  Eligibility

Ages Eligible for Study:   12 Months to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00568178

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

Additional Information:
No publications provided by Merck Sharp & Dohme Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00568178     History of Changes
Other Study ID Numbers: MK-0954-326, 2006-006415-74
Study First Received: December 3, 2007
Results First Received: August 11, 2009
Last Updated: March 16, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Proteinuria
Urination Disorders
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Enalapril
Enalaprilat
Amlodipine
Losartan
Maleic acid
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Calcium Channel Blockers
Membrane Transport Modulators
Vasodilator Agents
Anti-Arrhythmia Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on September 11, 2014