CRESTOR ® (ZD4522, rosuvastatin calcium) TABLETS Comments on Efficacy Joy Mele FDA Statistical Reviewer Division of Biometrics 2 Joy Mele FDA Statistical.

Slides:

Advertisements

Similar presentations

Labeling claims for patient- reported outcomes (A regulatory perspective) FDA/Industry Workshop Washington, DC September 16, 2005 Lisa A. Kammerman, Ph.D.

Advertisements

A Flexible Two Stage Design in Active Control Non-inferiority Trials Gang Chen, Yong-Cheng Wang, and George Chi † Division of Biometrics I, CDER, FDA Qing.

Statins in Renal Failure Andrea Fox Sunnybrook Health Science Center May 2010.

Design and analysis of clinical trials MULTIPLE COMPARISONS.

Robert K Huff PharmD. Candidate May Objectives The study was designed to examine 3 main aspects Biochemical effects Safety Tolerability Evacetrapib.

Impact of Prior Knowledge on Drug Development Decisions: Case studies across companies Jaap W Mandema, PhD Quantitative Solutions Inc. 845 Oak Grove Ave,

2003 0ctoberPharsight Copyright 1 Bridging Strategies using Clinical Trial Simulations D. Russell Wada Mountain View CA, USA The 4th Kitasato University-Harvard.

Simvastatin Increases HDL-C and Apolipoprotein A-1 Levels Significantly More Than Atorvastatin John P. Kastelein, Evan A. Stein, Michael A. Davidson, John.

Weng TC, et al. J Clin Pharm Ther 2010;35:

CE-1 CRESTOR ® Clinical Development Efficacy James W. Blasetto, MD, MPH Senior Director, Clinical Research.

Slide Source: Lipid and Lipoprotein Parameters at Baseline and Drug Treatment: METEOR Trial Baseline, Mean (SD) Time-Weighted Average.

* Plus–minus values are means ±SD. † Race was determined by the investigator. ‡ The body-mass index is the weight in kilograms divided by the square of.

ASTEROID A Study To evaluate the Effect of Rosuvastatin On Intravascular ultrasound- Derived coronary atheroma burden.

Role of Rosuvastatin in the Treatment of Dyslipidemia

Luveris ® New Drug Application ( ) Kate Meaker, M.S. Statistical Reviewer Division of Biometrics II Kate Meaker, M.S. Statistical Reviewer Division.

Power and Sample Size Determination Anwar Ahmad. Learning Objectives Provide examples demonstrating how the margin of error, effect size and variability.

Fenofibrate Intervention and Event Lowering in Diabetes FIELDFIELD Presented at The American Heart Association Scientific Sessions, November 2005 Presented.

BackgroundBackground HDL-C levels are inversely related to CV event rates. HDL-C levels are inversely related to CV event rates. Torcetrapib, a cholesteryl.

Rimonabant in Obesity Presented at American College of Cardiology Scientific Sessions 2004 Presented by Dr. Jean-Pierre Despres RIO LIPIDS Trial.

Drugs in the Body (1) Recurrence Relations A patient is given an initial dose of 50mg of a drug. Each hour the patient is given a 20mg tablet of the.

CI-1 CRESTOR ® (rosuvastatin calcium) Tablets Endocrinologic and Metabolic Drugs Advisory Committee Bethesda, Maryland July 9, 2003 C.

1 Statistics in Drug Development Mark Rothmann, Ph. D.* Division of Biometrics I Food and Drug Administration * The views expressed here are those of the.

SATURN: Objective To compare the effects of rosuvastatin 40 mg versus atorvastatin 80 mg on progression of coronary atherosclerosis assessed by intravascular.

Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 2 ARBITER-2 Trial Presented at The American Heart Association Scientific.

Endocrinologic & Metabolic Drugs Advisory Committee Meeting

Collaborative Atorvastatin Diabetes Study CARDS Dr Sachin Kadoo.

Baseline Patient Characteristics Bart A.N. Verhoeven, et al. Stroke 2006;37:

Chemical Structure of Rosuvastatin Relative lipophilicity * Rosuvastatin Cerivastatin Simvastatin Fluvastatin Atorvastatin Pravastatin.

Zometa for Prostate Cancer Bone Metastases Protocol 039 Amna Ibrahim, M.D. Oncology Drug Products FDA.

Lipitor Time Of Day Cheap Atorvastatin Canadian Pharmacy pfizer lipitor recall fda common lipitor doses fimasartan atorvastatin is lipitor a simvastatin.

DIABETES INSTITUTE JOURNAL CLUB CARINA SIGNORI, D.O., M.P.H. DECEMBER 15, 2011 Atherothrombosis intervention in metabolic syndrome with low HDL/High Triglycerides:

The Heart Outcomes Prevention Evaluation (HOPE) – 3 Trial

Drug Interactions Lipitor Azithromycin Atorvastatin Cost muscle aches associated with lipitor lipitor medicijnen lipitor generic callback lipitor emagrece.

Atorvastatin Ir Tablet Order Atorvastatin Online crestor vs lipitor study is lipitor a class c medication class action lawsuits for lipitor lipitor pungi.

Double-blind, randomized trial in 4,162 patients with Acute Coronary Syndrome

1 Clinical Studies Section of Labeling Joseph Porres, M.D., Ph.D. Medical Officer Division of Dermatologic and Dental Drug Products FDA.

An Alternative to Data Imputation in Analgesic Clinical Trials David Petullo, Thomas Permutt, Feng Li Division of Biometrics II, Office of Biostatistics.

Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated.

Buy Crestor buy crestor 5mg online crestor online cheap buy crestor 20 mg buy crestor 40 mg cheap crestor 10mg cheap crestor 40 mg cheap rosuvastatin calcium.

Baseline characteristics and effectiveness results

Neal B, et al. Diabetes Care 2015;38:403–411

REVEAL: Randomized placebo-controlled trial of anacetrapib in 30,449 patients with atherosclerotic vascular disease Louise Bowman on behalf of the HPS.

Effects of Anacetrapib on the Incidence of New-Onset Diabetes Mellitus and on Vascular Events in People With Diabetes Louise Bowman & Martin Landray on.

Intensive Statin Recommendations

Senior Medical Director, Cardiovascular

First time a CETP inhibitor shows reduction of serious CV events

SPIRE Program: Studies of PCSK9 Inhibition and the Reduction of Vascular Events Unanticipated attenuation of LDL-c lowering response to humanized PCSK9.

Treatment LDL-C: baseline (mg/dL) LDL-C: 24 mo (mg/dL) p

Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 monoclonal antibody alirocumab vs placebo in patients with heterozygous familial.

Efficacy of alirocumab in high cardiovascular risk populations with or without heterozygous familial hypercholesterolemia: Pooled analysis of eight ODYSSEY.

An International Atherosclerosis Society Position Paper: Global recommendations for the management of dyslipidemia-Full report Scott M. Grundy, Hidenori.

Overview. 5 Things You Need to Know About Statin Selection in Patients With HIV Infection.

Section 7: Aggressive vs moderate approach to lipid lowering

% decrease in LDL-C at 24 weeks from baseline

Efficacy and safety of naproxcinod in the treatment of patients with osteoarthritis of the knee: a 13-week prospective, randomized, multicenter study

% decrease in LDL-C at 24 weeks from baseline

ODYSSEY FH I and II Trial design: Participants with heterozygous familial hypercholesterolemia on statin therapy were randomized to alirocumab 75 mg SQ.

Screening, Lipid Stabilization, and Placebo Run-in

LRC-CPPT and MRFIT Content Points:

HOPE-3 Trial design: Patients without known cardiovascular disease, and with an intermediate risk of cardiovascular events, were randomized in a 2 x 2.

Body mass, BMI, plasma lipids, lipoproteins, and glucose homeostasis at baseline, and following placebo and rosuvastatin periods Dmitri Sviridov et al.

RUTHERFORD-2 Trial design: Patients with heterogeneous familial hypercholesterolemia (HeFH) on statins were randomized in a 2:2:1:1 fashion to subcutaneous.

Major classes of drugs to reduce lipids

Updates on Dyslipidemia

SPIRE Program: Studies of PCSK9 Inhibition and the Reduction of Vascular Events Unanticipated attenuation of LDL-c lowering response to humanized PCSK9.

TNT diabetes analysis: Baseline and final LDL cholesterol levels

Section 6: Update on lipid treatment guidelines

Late-Breaking Data on LDL-C Reduction

Presentation transcript:

CRESTOR ® (ZD4522, rosuvastatin calcium) TABLETS Comments on Efficacy Joy Mele FDA Statistical Reviewer Division of Biometrics 2 Joy Mele FDA Statistical Reviewer Division of Biometrics 2 Center for Drug Evaluation and Research

2 Comments on Efficacy Rosuvastatin Effect on LDL –Studies 8, 33 and 65 Comparison of Rosuvastatin and Atorvastatin –Studies 33 and 65 Rosuvastatin Effect on HDL Rosuvastatin Effect on LDL –Studies 8, 33 and 65 Comparison of Rosuvastatin and Atorvastatin –Studies 33 and 65 Rosuvastatin Effect on HDL

3 Three Dose Response Studies Type IIa/IIb Patients Study Doses Sample Size Baseline LDL per arm 8 ROSU ~ ROSU ~191 ATOR ROSU ~189 ATOR Study Doses Sample Size Baseline LDL per arm 8 ROSU ~ ROSU ~191 ATOR ROSU ~189 ATOR 10-80

4 LDL Mean % Change from Baseline for the Dose Range of Rosuvastatin

5 Comparability of Rosuvastatin and Atorvastatin Rosuvastatin is significantly more potent on mg per mg basis What doses are comparable? –2x? 4x? Treatment difference and 95% CI Rosuvastatin is significantly more potent on mg per mg basis What doses are comparable? –2x? 4x? Treatment difference and 95% CI

6 Rosuvastatin vs. 2x Atorvastatin Studies LDL % change from baseline Treatment Differences and 95% CI

7 Rosuvastatin 40 vs. Atorvastatin 80 Study 65 - LDL % Change from Baseline LOCF

8 Rosuvastatin vs. 4x Atorvastatin Studies LDL % change from baseline Mean Treatment Differences and 95% CI

9 HDL % Change from Baseline Rosuvastatin Compared to Placebo Study BSL ~50 +3% +13% +14% +8% +9% 23 ~55 +3% +11% +15% 24 ~49 +4% +12% +12% 35 ~35 -2% +4% +6% +18% +15% +10% Treatment group n<30 in Studies 8, 23 and 35; ~128 in Study 24 Study BSL ~50 +3% +13% +14% +8% +9% 23 ~55 +3% +11% +15% 24 ~49 +4% +12% +12% 35 ~35 -2% +4% +6% +18% +15% +10% Treatment group n<30 in Studies 8, 23 and 35; ~128 in Study 24

10 HDL % Change from Baseline for Atorvastatin and Rosuvastatin Study 65 Type IIa/IIb

11 SummarySummary Rosuvastatin achieves about 4% more mean LDL-lowering than 2 times the dose of atorvastatin The HDL effects are variable –No dose response relationship Small increase for 20 mg over 10 mg –Consistent with the statin class Rosuvastatin achieves about 4% more mean LDL-lowering than 2 times the dose of atorvastatin The HDL effects are variable –No dose response relationship Small increase for 20 mg over 10 mg –Consistent with the statin class