Table of Contents
AvandiaŽ (rosiglitazone maleate)
AvandiaŽ SmithKline Beecham Pharmaceuticals
AvandiaŽ - Key Messages
AvandiaŽ Preclinical Findings - Highlights
PPAR? is a Key Molecular Target for Thiazolidinediones
Rosiglitazone - Preclinical Efficacy
Preclinical Findings Common to Thiazolidinediones
Preclinical Findings Common to Thiazolidinediones
Differences in Pharmacological Potency
Differences in Hepatic Safety Profile
PPT Slide
Efficacy and Safety Predictions from Preclinical Studies
AvandiaŽ SmithKline Beecham Pharmaceuticals
AvandiaŽ (rosiglitazone maleate)
AvandiaŽ Data Presentation
AvandiaŽ Phase 2/3 Clinical Program
Dose-response of AvandiaŽ in Monotherapy
Change from Baseline in FPG at Week 8 (Pooled Monotherapy Data)
AvandiaŽ Monotherapy
Monotherapy Study Design
011: Baseline Demographic Characteristics
011: Baseline Metabolic Characteristics
011: FPG at Week 26
011: HbA1c at Week 26
024: FPG at Week 26
024: FPG Responders
024: HbA1c at Week 26
024: HbA1c by Prior Therapy
Monotherapy Summary
Monotherapy Summary
AvandiaŽ Durability of Effect
020: Study Design Double-blind, double-dummy
020: FPG Over Time
020: HbA1c Over Time
020: Hypoglycemia
020: Endogenous Insulin Parameters - Change from Baseline at Week 52 Expressed as a Percentage of Baseline
Monotherapy Summary
Monotherapy Summary
AvandiaŽ - Lipid Effects
020: LDL-C Over Time
020: HDL-C Over Time
020: LDL-C/HDL-C Over Time
020: Triglycerides Over Time
020: Free Fatty Acids Over Time
Monotherapy Summary
Monotherapy Summary
Monotherapy Summary
Monotherapy Summary
AvandiaŽ Combination with Metformin
094 and 093: Eligible Patients
094: Study Design
094: Baseline Metabolic Characteristics
094: FPG at Week 26
094: FPG Responders
094: HbA1c at Week 26
093: Study Design The Synergy Study
093: FPG at Week 26 Compared to Baseline
093: FPG Responders
093: HbA1c at Week 26 Compared to Baseline
HbA1c - Treatment Effect (95% CI) Monotherapy
HbA1c - Treatment Effect (95% CI) - AvandiaŽ + Metformin
Conclusions
Conclusions
Conclusions
Conclusions
Conclusions
Conclusions
Conclusions
AvandiaŽ SmithKline Beecham Pharmaceuticals
AvandiaŽ (rosiglitazone maleate)
AvandiaŽ Clinical Program Safety Profile
AvandiaŽ Studies
AvandiaŽ Safety Database Phase 2/3 Clinical Program
AvandiaŽ Safety Database- Patient Years of Treatment
Characteristics of the Safety Populations
Clinical Characteristics of the Safety Population
Frequency of Concomitant Medication Use in the Study Population
Percent of Patients with One or More Adverse Event Report
Most Frequent Adverse Events in Double-blind Trials - AvandiaŽ Monotherapy
Most Frequent Adverse Events in Double-blind Trials - AvandiaŽ in Combination with Sulfonylureas
Most Frequent Adverse Events in Double-blind Trials - AvandiaŽ in Combination with Metformin
Analysis of AEs in Patient Sub-Groups
Adverse Events Leading to Withdrawal
Summary of Serious Non-fatal Adverse Experiences
Reported Deaths
Adverse Event Summary
Areas of Interest Based on Preclinical Findings
Areas of Interest Based on Preclinical Findings
Hemodynamic/Cardiovascular Effects
Echocardiography Study- 080
Echocardiography Study- 080
Mean LVMI at Baseline, Week 28 and Week 52
Echocardiography Results
Mean Ejection Fraction at Baseline, Week 28 and Week 52
Change in Mean 24 Hour Ambulatory Blood Pressure- 080 (Baseline to Week 52 - All Randomized [OC] Population )
Cardiovascular Serious Adverse Experiences -
Deaths Attributed to Cardiac Events
Cardiac Mortality Comparison to Other Clinical Trials and Observational Studies
Frequency of Edema in Double-blind Studies
Hemodynamic / Cardiovascular Conclusions
Areas of Interest Based on Preclinical Findings
Hematology
020: Mean Hematocrit Over Time
Anemia Adverse Events
Criteria for Hemoglobin and Hematocrit Assessment
Percentage of Patients Below Threshold Values for Hemoglobin or Hematocrit
PPT Slide
PPT Slide
Summary: Hematology
Areas of Interest Based on Preclinical Findings
Weight
Weight Mean Change (kg) from Baseline to Week 52
Weight Conclusions
Area of Special Interest
Liver Safety
Study Entry Criteria & Monitoring
ALT Levels > 3x ULRR in the AvandiaŽ Clinical Program
PPT Slide
006.003.00359 AvandiaŽ 1mg bd
024.030.02644 - 105.022.60241 Placebo / AvandiaŽ 8mg od
Two Patients with Jaundice
Liver - Summary
AvandiaŽ Conclusions: Safety Profile
AvandiaŽ SmithKline Beecham Pharmaceuticals
AvandiaŽ (rosiglitazone maleate)
AvandiaŽ: 5 Main Points
AvandiaŽ: 5 Main Points
Type 2 Diabetes: Lessons from UKPDS*
Type 2 Diabetes: Lessons from UKPDS
AvandiaŽ: 5 Main Points
AvandiaŽ: Insulin Sensitizer in Preclinical Studies
AvandiaŽ: 5 Main Points
HbA1c - Treatment Effect (95% CI) Monotherapy
Hypoglycemic Effect is Durable and Clinically Significant
AvandiaŽ: Insulin Sensitizer in Man
AvandiaŽ: Insulin Sensitizer in Man
AvandiaŽ: 5 Main Points
No Evidence of Hepatotoxicity
AvandiaŽ: 5 Main Points
Cardiovascular Lipid Profile
Hemodynamic Effects
Avandia: Conclusion
Positive Risk / Benefit Assessment
AvandiaŽ SmithKline Beecham Pharmaceuticals
AvandiaŽ (rosiglitazone maleate)
AvandiaŽ - Profile
AvandiaŽ - Efficacy
AvandiaŽ - Efficacy
AvandiaŽ - Safety
AvandiaŽ - Safety
AvandiaŽ Proposed Indications
AvandiaŽ (rosiglitazone maleate)
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