COZAAR™ (losartan) in Type 2 Diabetes and Nephropathy

4/15/02


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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

Author: Lee W. Potts