1 / 121

台灣武田藥品工業股份有限公司

台灣武田藥品工業股份有限公司. ACTOS Clinical Trials. ACTOS Clinical Trials. PROACTIVE PRO spective Pioglit A zone C linical T rial I n Macro V ascular E vents. ACTOS Clinical Trials. PROACTIVE. Objective : Evaluate Effects of Pioglitazone in High-Risk Patients

jaxon
Download Presentation

台灣武田藥品工業股份有限公司

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. 台灣武田藥品工業股份有限公司

  2. ACTOS Clinical Trials

  3. ACTOS Clinical Trials PROACTIVE PROspective PioglitAzone Clinical Trial In MacroVascular Events

  4. ACTOS Clinical Trials PROACTIVE Objective : Evaluate Effects of Pioglitazone in High-Risk Patients  To evaluate whether pioglitazone reduce total mortality and macrovascular morbidity in high-risk patients with type 2 diabetes  To further characterize the safety of pioglitazone in this group of patients

  5. ACTOS Clinical Trials PROACTIVE Design :  5,420 patients  Randomized、Double-blind 、Multicenter 、 Placebo-controlled 、Parallel-group  Dose escalation to maximum 45 mg pioglitazone

  6. ACTOS Clinical Trials PROACTIVE Primary :  All-cause mortality Endpoints  Nonfatal myocardial infarction (MI)- including silent MI  Acute coronary syndrome  Coronary artery bypass surgery (CABG)  Stroke  Leg amputation  Bypass surgery or revascularization in the leg

  7. ACTOS Clinical Trials PROACTIVE Secondary :  Individual components of the primary Endpoints endpoints  Cardiovascular mortality

  8. ACTOS Clinical Trials CHICAGO A Study Evaluating Carotid Intima-Media THICkness (CIMT) in Atherosclerosis Using PioGlitazOne

  9. ACTOS Clinical Trials CHICAGO Objective : Compare Effects on Rate of Progression of Atherosclerosis – Pioglitazone vs Glimepiride Design :  400 patients  Randomized、Double-blind 、Multicenter  Dose escalation to maximum 45 mg pioglitazone or 4 mg glimepiride

  10. ACTOS Clinical Trials CHICAGO Primary : Absolute change in CIMT from baseline Endpoints to final visit Secondary :  Occurrence of new or exacerbated Endpoints congestive heart failure (CHF)  Occurrence of cardiovascular events as a composite of – Cardiovascular mortality、Fatal and nonfatal stroke

  11. ACTOS Clinical Trials PERISCOPE Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation

  12. ACTOS Clinical Trials PERISCOPE Objective : To evaluate the effect of Pioglitazone vs Glimepiride on the rate of progression of coronary atherosclerotic disease as measured by intravascular ultrasound (IVUS) Design :  600 patients  Randomized、Double-blind 、Multicenter  Dose escalation to maximum 45 mg pioglitazone or 4 mg glimepiride

  13. ACTOS Clinical Trials PERISCOPE Primary : Percent change in coronary artery Endpoints atheroma volume using IVUS imaging of coronary arteries Secondary :  Occurrence of new or exacerbated Endpoints congestive heart failure (CHF)  Occurrence of cardiovascular events as a composite of – Cardiovascular mortality、Fatal and nonfatal stroke

  14. ACTOS Clinical Trials PURE I Pioglitazone in Heart FailURE ( NYHA Class I )

  15. ACTOS Clinical Trials PURE I Objective : Compare Cardiac Safety in Patients With Type 2 Diabetes and Mild Cardiac Disease - Pioglitazone vs Glyburide Design :  300 patients  Randomized、Double-blind 、Multicenter  Dose escalation to maximum 45 mg pioglitazone or 15 mg glyburide

  16. ACTOS Clinical Trials PURE I Primary : Change in walking distance during a Endpoints standardized 6 – minute walk test Secondary :  Morbidity and mortality due to Endpoints cardiovascular events  Change in cardiac structure and function as measured by echocardiograph analysis  A1c、 FPG 、BP 、Body Weight

  17. ACTOS Clinical Trials BARI 2D Bypass Angioplasty Revascularization Investigation in Type 2Diabetes NIH – Sponsored Study

  18. ACTOS Clinical Trials BARI 2D Objective : Compare Effects of Angioplasty or Bypass Surgery With a Medical Program Determine Survival Outcomes of Increasing Insulin Levels vs Decreasing Insulin Resistance Design :  2,600 patients  Randomized、Multicenter  5 – year duration

  19. ACTOS Clinical Trials BARI 2D Primary : In 5 years, all-cause mortality Endpoints Secondary : Combined endpoint of : Endpoints  Death  Q wave myocardial infarction (MI)  Stroke

  20. ACTOS Cardiovascular Clinical Trials Timeline

  21. Pioglitazone HCl - Actos Scientific Posters、Presentations、Abstracts 2003

  22. Pioglitazone HCl - Actos Scientific Posters、Presentations、Abstracts 2003 • American Association of Clinical Endocrinologists ( AACE ) – May 14~18 : San Diego, CA • International Society for Pharmacoeconomics and Outcomes Research ( ISPOR ) – May 18~21 : Arlington, VA • American Diabetes Association ( ADA ) – June 13~19 : New Orleans, LA

  23. Pioglitazone HCl - Actos Scientific Posters、Presentations、Abstracts 2003 • The Endocrine Society ( ENDO ) – June 19~22 : Philadelphia, PA • International Diabetes Federation ( IDF ) – August 24~29 : Paris, France

  24. AACE Reductions of Alanine Transaminase Levels in Patients with Type 2 Diabetes Mellitus Treated with Pioglitazone Plus Sulfonylurea or Metformin or Insulin

  25. AACE Objective :To evaluate the effect of pioglitazone (PIO) plus sulfonylurea (SU) or metformin (MET) or Insulin on ALT levels. Design :  2,219 patients  24-Week Randomized、Multicenter  (30 or 45 mg) of PIO plus SU or MET or Insulin

  26. AACE

  27. AACE Total of 2,219 participants, 5 subjects (0.22%) had an adverse event of 3X the upper limit of normal increased ALT

  28. ADA - 2 Long-term Effects of Pioglitazone and Glibenclamide on Serum Lipids in Patients with Type 2 Diabetes

  29. ADA - 2 Objective:To compare the long-term effects of PIO and GLB on lipid profiles, glycemic control, and insulin sensitivity in patients with T2D.

  30. ADA - 2

  31. ADA - 2 Effect of PIO and GLB on Lipoprotein-related Cardiovascular Risk Parameters Key Point: Long-term (52-week) treatment with PIO significantly reduced AIP and Total Cholesterol/HDL-C compared with GLB

  32. ADA - 2 Effect of PIO and GLB on HOMA-S Key Point: PIO significantly enhanced insulin sensitivity compared with baseline and GLB, as measured by HOMA-S, whereas GLB significantly decreased insulin sensitivity.

  33. ADA - 2 Time-course of Effect on A1C Key Point: The reduction in A1C by pioglitazone was less rapid but more sustained compared with GLB.

  34. ADA - 2 Effect of PIO and GLB on Safety Variables Key Point: PIO produced more weight gain and edema, but less hypoglycemia than GLB.

  35. ADA - 2 • Conclusions : • Compared with GLB, PIO significantly improved HDL-C and TG, without producing a significant increase in total cholesterol or LDL-C. • Compared with GLB, PIO reduced AIP and total cholesterol/HDL-C. • Compared with GLB, PIO had beneficial effects on lipid profiles and insulin sensitivity (as assessed by HOMA-S) despite producing more weight gain than GLB.

  36. ADA • Quartet studies • Four large European randomized, double-blind clinical trials over one year (over 3,700 patients). • 25 countries across Europe, Australia, South Africa, and Canada.

  37. ADA - 3 Results of Liver Safety Testing in 3713 Type 2 Diabetic Patients Treated for One Year in Double-Blind Controlled Trials with Pioglitazone, Metformin or Gliclazide Quartet studies

  38. ADA - 3 Objective:To compare liver test results in patients treated with thiazolidinedione pioglitazone with those treated with metformin or a sulphonylurea, gliclazide. Quartet studies

  39. ADA - 3 • Design : • Four large European randomized, double-blind clinical trials over one year (over 3,700 patients). • Two trials used monotherapy treatments (pioglitazone vs metformin and pioglitazone vs gliclazide) • Two trials studied combination therapies • (pioglitazone + metformin vs gliclazide + metformin) • (pioglitazone + SU vs metformin + SU ). Quartet studies

  40. ADA - 3 Mean Changes in Liver Tests Pioglitazone(n = 1,857); non-pioglitazone: gliclazide or metformin (n = 1,856)

  41. ADA - 3 Mean Changes in Liver Tests Pioglitazone(n = 1,857); non-pioglitazone: gliclazide or metformin (n = 1,856)

  42. ADA - 3 Percentage Changes from Baseline Over Time in (ALT) Pioglitazone(n = 1,857); non-pioglitazone: gliclazide or metformin (n = 1,856)

  43. ADA - 3 • Conclusions : • Reduction in insulin resistance with pioglitazone treatment results in improvement of liver testing results. Quartet studies

  44. ADA - 4 Favourable Effects of Pioglitazone Mono or Combination Therapy on the Atherogenic Index of Plasma – A Surrogate Marker of LDL Particle Size Quartet studies

  45. ADA - 4 • Background : • The atherogenic index of plasma (AiP) is inversely correlated with LDL particle size and can be used as an indirect measurement of LDL atherogenic power. • AiP was calculated as the log10 ( TG / HDL-C ) • The aim of the current analysis was to assess if pioglitazone would influence AiP. Quartet studies

  46. ADA - 4 Mean Change (± SEM) from Baseline in AiP Quartet studies

  47. ADA - 4 • Conclusions : • The improvement in AiP was greater with Pioglitazone than with MET or GLUC as either monotherapy or combination. • The favorable change in the size of LDL particles with Pioglitazone, which may reduce the atherogenicity of LDL in patients with type 2 diabetes. • Pioglitazone may cause a shift from small dense to large more buoyant LDL particles. This may have implications on atherogenesis and other cardiovascular risks. Quartet studies

  48. ADA - 5 The Effects of Pioglitazone, Metformin and Gliclazide as Monotherapy or in Combination on 3-Hour OGTT Investigations Quartet studies

  49. ADA - 5 • Background : • Previous trials have measured the impact of Pioglitazone on OGTT after 16 and 24 weeks. However, no data exists showing the potential long-term benefits. • The aim of the present analysis was to investigate the effectiveness of Pioglitazone in reducing post-load glucose levels after 52 weeks using 3-hour OGTT. Quartet studies

  50. ADA - 5 Study Design Quartet studies

More Related