Table of Contents
COZAAR™ (losartan) in Type 2 Diabetes and Nephropathy
RENAAL
RENAAL
COZAAR™ (losartan): Proposed New Indication
Evidentiary Standard for Approvals Based Primarily on a Single Study
Use of a Single Study to Support a New Claim Points to Consider for COZAAR
COZAAR™ (losartan): Proposed New Indication
COZAAR™ (losartan) in Type 2 Diabetes and Nephropathy
Merck Consultants
Merck Consultants
Losartan in Type 2 Diabetes and Nephropathy
Losartan in Type 2 Diabetes and Nephropathy Agenda
End-Stage Renal Disease: An Unmet Medical Need
Diabetic Nephropathy
Theoretical Hemodynamic Role of Angiotensin II in Diabetic Glomerular Injury
Theoretical Non-Hemodynamic Role of Angiotensin II in Diabetic Glomerular Injury
Preclinical Renal Data: Blockade of Angiotensin II System
Clinical Renal Outcomes Data: Renin-Angiotensin System Blockade in Diabetic Nephropathy
Factors that Differentiate Type 2 from Type 1 Diabetic Patients
Current Clinical Approaches to Delay Progression to ESRD in Type 2 Diabetes
Primary Study Question in RENAAL
RENAAL
RENAAL: Study Organization
RENAAL: Primary Hypothesis
Progression of Renal Disease in Type 2 Diabetes
RENAAL: Secondary Hypotheses
RENAAL: Key Inclusion/Exclusion Criteria
RENAAL: Study Design (I)
RENAAL: Study Design (II)
RENAAL: Study Design (III)
RENAAL: Early Study Termination
Agenda
RENAAL: Patient Disposition
RENAAL: Baseline Demographics (I)
RENAAL: Baseline Demographics (II)
RENAAL: Medical History at Baseline
RENAAL: Selected Mean Baseline Laboratory Values
RENAAL: Primary Hypothesis
RENAAL: Analysis of Primary Composite Endpoint
RENAAL: Analysis of Primary Composite Endpoint
RENAAL: Primary Composite Endpoint
RENAAL: Analysis of Irreversible Clinical Endpoints (Pre-specified)
RENAAL: Analysis of Irreversible Clinical Endpoints (Pre-specified)
RENAAL: Analysis of Irreversible Clinical Endpoints (Pre-specified)
RENAAL: Analysis of Irreversible Clinical Endpoints (Pre-specified)
RENAAL: Irreversible Clinical Endpoints (I)
RENAAL: Irreversible Clinical Endpoints (II)
RENAAL: Irreversible Clinical Endpoints (III)
RENAAL: Summary of Primary Composite and Clinical Endpoints
RENAAL: Imbalance in Baseline Risk
RENAAL: Distribution of Baseline Proteinuria by Stratum
RENAAL: Distribution of Baseline Proteinuria within Strata
RENAAL: Risk for Primary Composite Endpoint Rises with Increasing Baseline Proteinuria
RENAAL: Risk for Primary Composite Endpoint Rises with Increasing Baseline Proteinuria
RENAAL: Primary Composite Endpoint Adjusted by Baseline Proteinuria (post hoc)
RENAAL: Endpoints Adjusted for Baseline Proteinuria as a Continuous Covariate (post hoc)
RENAAL: Pre-defined Sensitivity Analyses
RENAAL: Blood Pressure Control
RENAAL: Concurrent Antihypertensive Medications
RENAAL: Comparable Blood Pressure (Trough) Control Between Treatment Groups
RENAAL: Mean Arterial Pressure
RENAAL: Endpoints Adjusted for Mean Arterial Blood Pressure
RENAAL: Baseline Subgroups
RENAAL: Baseline Subgroups
RENAAL: Secondary Hypotheses (Renal)
RENAAL: Reduction in the Rate of Loss of Renal Function (On-treatment Approach)
RENAAL: Losartan Reduces Proteinuria (On-treatment Approach)
RENAAL: Efficacy Summary (Renal)
Agenda
RENAAL: Secondary Hypotheses (Cardiovascular)
RENAAL: Secondary Cardiovascular Composite Endpoint
RENAAL: Secondary Cardiovascular Composite Endpoint and Components
RENAAL: Composite of ESRD/MI/Stroke/Death (post hoc)
RENAAL: Summary of Cardiovascular Data
Agenda
RENAAL: Clinical Adverse Experience Summary
RENAAL: Laboratory Adverse Experience Summary
RENAAL: Pre-specified Analysis of Adverse Experiences
RENAAL: Distribution of Serum Potassium Values at Each Time Point
RENAAL: Serum Potassium at Any Time During the Study
RENAAL: Hyperkalemia
RENAAL: Summary of Safety
RENAAL: Review of Evidence and Conclusions
RENAAL: Strength of the Evidence
RENAAL: Robust Study Design
RENAAL: Clinically Important and Statistically Significant Results
RENAAL: Imbalance in Baseline Risk
RENAAL: Clinically Important and Statistically Significant Results
RENAAL: Renal Protective Effects and Blood Pressure Control
RENAAL: Clinically Important and Statistically Significant Results
RENAAL: Secondary Cardiovascular Composite Endpoint and Components
Conclusions
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