A Placebo-Controlled Trial of Prucalopride for Severe Chronic Constipation Michael Camilleri, M.D., Rene Kerstens, M.Sc., An Rykx, Ph.D., and Lieve Vandeplassche,

Slides:

Advertisements

Similar presentations

Srdan (Serge) Verstovsek M.D., Ph.D. Professor of Medicine Department of Leukemia University of Texas MD Anderson Cancer Center Houston, Texas, USA JAK.

Advertisements

CONSENSUS: Cooperative North Scandinavian Enalapril Survival Study Purpose To determine whether the ACE inhibitor enalapril reduces mortality in patients.

Purpose To determine whether metoprolol controlled/extended release

TROPHY TRial Of Preventing HYpertension. High-normal BP increases CV risk Vasan RS et al. N Engl J Med. 2001;345: Incidence of CV events in women.

The ERICA Trial Peter H. Stone, MD, FACC, Nikolay A. Gratsiansky, MD, Alexey Blokhin, MD, I-Zu Huang, MD, Lixin Meng, MS, MPH, for the ERICA Investigators.

Prevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia James Shepherd, M.D., Stuart M. Cobbe, M.D., Ian Ford, Ph.D., Christopher.

Clinical Observation of Montelukast as a Partner Agent for Complementary Therapy.

The ONTARGET Trial Reference The ONTARGET investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358:15.

Reference Cooper BA, and the IDEAL study group. A randomized controlled trial of early versus late initiation of dialysis. N Engl J Med [Accessed.

CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved Purpose To determine whether the angiotensin.

BEAUTI f UL: morBidity-mortality EvAlUaTion of the I f inhibitor ivabradine in patients with coronary disease and left ventricULar dysfunction Purpose.

Randomized, double-blind, multicenter, controlled trial.

Comparison of Nilotinib and Imatinib in Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP): ENESTnd Beyond One Year Larson.

Clinical trial 2. Objective To evaluate efficacy and safety of varenicline for smoking cessation compared with sustained-release bupropion (bupropion.

Management of Constipation in Adults Stephen Aglubat, MD May 2012.

Slide 1 EZT 2002-W-6022-SS Ezetimibe Co-administered with Statins: Efficacy and Tolerability Copyright © 2003 MSP Singapore Company, LLC. All rights reserved.

Switch NNRTI to NNRTI  Switch EFV to ETR –CNS toxicity study –Patient’s preference study.

Laura Mucci, Pharm.D. Candidate Mercer University 2012 Preceptor: Dr. Rahimi February 2012.

CAST: Cardiac Arrhythmia Suppression Trial Purpose To determine whether therapy with class Ic antiarrhythmics to suppress asymptomatic or mildly symptomatic.

AIRE: Acute Infarction Ramipril Efficacy study Purpose To determine whether the ACE inhibitor ramipril reduces mortality in patients with evidence of heart.

BEST: Beta-blocker Evaluation Survival Trial Purpose To determine whether the β-blocker bucindolol reduces morbidity and mortality in patients with advanced.

CI-1 Zelnorm ® (tegaserod maleate) Gastrointestinal Drugs Advisory Committee Meeting July 14, 2004 Gastrointestinal Drugs Advisory Committee Meeting July.

1 1 Zelnorm ® (tegaserod maleate) Advisory Committee Presentation Gastrointestinal Drugs July 14, 2004.

Cardiovascular Risk and NSAIDs Arthritis Advisory Committee Meeting November 29, 2006 Sharon Hertz, M.D. Deputy Director Division of Analgesia, Anesthesia,

Bowel Trouble? By: Stephanie Adams. Interesting Facts Feeling Plugged up? ◦ It is normal for people to experience short periods of constipation. ◦ About.

LIPID: Long-term Intervention with Pravastatin in Ischemic Disease Purpose To determine whether pravastatin will reduce coronary mortality and morbidity.

HOPE: Heart Outcomes Prevention Evaluation study Purpose To evaluate whether the long-acting ACE inhibitor ramipril and/or vitamin E reduce the incidence.

Clinical trial 2. Objective To evaluate efficacy and safety of varenicline for smoking cessation compared with sustained-release bupropion (bupropion.

ICSA2007 Symposium, 6/5/07 Panel Session Shuyen Ho First Example in Respiratory Area  Steroid Nasal Spray  Seasonal Allergic Rhinitis, Age  12 yr 

Clinical Trial Results. org Anti-Inflammatory Effects of Pioglitazone and/or Simvastatin in High Cardiovascular Risk Patients With Elevated High Sensitivity.

Sprout Pharmaceuticals Inc. FDA Approval Date: August 18, 2015

IN 1 NDA Gastrointestinal Advisory Committee Meeting Gaithersburg, Maryland June 26, 2000 Gastrointestinal Advisory Committee Meeting Gaithersburg,

CE-1 Zelnorm ® (tegaserod maleate) Efficacy and Safety in Chronic Constipation Eslie Dennis, MD Senior Medical Director: Gastroenterology Clinical Development.

EF 1 Efficacy and Safety Martin P. Lefkowitz, MD Director, Clinical Research Martin P. Lefkowitz, MD Director, Clinical Research.

C-1 Efficacy of the Combination: Meta-Analyses Donald A. Berry, Ph.D. Frank T. McGraw Memorial Chair of Cancer Research University of Texas M.D. Anderson.

Angelo L Gaffo Kenneth G Saag Core Evidence 2009:4 25–36

Patient presenting with symptoms of constipation Identify causeIdentify cause. Consider disease, drugs, pregnancy, immobility, psychological problems Confirm.

4S: Scandinavian Simvastatin Survival Study

Thrice-Weekly Glatiramer Acetate for Relapsing Forms of Multiple Sclerosis: Findings from the GALA Study Fred D. Lublin, MD Saunders Family Professor of.

Conclusions Sidney Cohen, MD Chairman, Department of Medicine Temple University School of Medicine Philadelphia, Pennsylvania Sidney Cohen, MD Chairman,

Downloaded from Slide 1 Dual Inhibition of Two Sources of Cholesterol: Absorption and Production Results of a Clinical Trial.

COPERNICUS: Carvedilol Prospective Randomized Cumulative Survival trial Purpose To assess the effect of carvedilol, a β 1 -, β 2 - and α 1 -receptor blocker,

Effects of 1-H-indole-3-glyoxamide (A-002) on concentration of secretory phospholipase A2 (PLASMA study): a phase II double-blind, randomised,placebo-controlled.

내과 R2 이지훈 N Engl J Med Sep 8.

Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease (HOPE-3 trial) R4. 박은지 / PF. 정혜문 Salim Yusuf, M.B., B.S., D.Phil.,

Effect of Spironolactone on Diastolic Function and Exercise Capacity in Patients with Heart Failure with preserved Ejection Fraction Effect of Spironolactone.

Insulin pump treatment compared with multiple daily injections for treatment of type 2 diabetes (OpT2mise): a randomized open-label controlled trial Yves.

Lactobacillus reuteri DSM for the management of infantile colic in breastfed infants A randomized, double-blind, placebo-controlled trial.

Robert A. Terkeltaub, Daniel E. Furst, Katherine Bennett, Karin A. Kook, R. S. Crockett, and Matthew W. Davis ARTHRITIS & RHEUMATISM Vol. 62, No. 4, April.

Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation Manesh R. Patel, M.D., Kenneth W. Mahaffey, M.D., Jyotsna Garg, M.S., Guohua Pan, Ph.D.,

A Phase 3 Trial of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis N ENGL J MED. May 18, /NEJMoa Talmadge E. King, Jr., M.D.,

1 Once-daily indacaterol versus twice-daily salmeterol for COPD ; a placebo-controlled comparison R2 정명화 Eur Respir J 2011; 37: 273–279.

GASTROENTEROLOGY 2008; 134 :688–695 소화기내과 R4 이 재 연.

Manesh R. Patel, M.D., Kenneth W. Mahaffey, M.D., Jyotsna Garg, M.S., Guohua Pan, Ph.D., Daniel E. Singer, M.D., Werner Hacke, M.D., Ph.D., Gunter Breithardt,

Journal Conference Hepatology 2009;50: Background.

Statins The AURORA Trial Reference Fellstrom BC. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009;360. A.

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

Everolimus for Advanced Pancreatic Neuroendocrine Tumors N Engl J Med 2011;364: R4. 박선희 / Prof. 동석호.

1 Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation R3 Dae Ho Kim / Prof. Jin Bae Kim N Engl J Med 2011; DOI: Manesh R. Patel, M.D.,

Cardiovascular Disease and Antihypertensives The RENAAL Trial Reference Brunner BM, and the RENAAL study group. Effects of losartan on renal and cardiovascular.

Telbivudine Versus Lamivudine in Chinese Patients with Chronic Hepatitis B: Results at 1 Year of a Randomized, Double-Blind Trial HEPATOLOGY 2008;47:

Multicenter, Placebo-Controlled Trial

Nymox Pivotal Phase 3 Fexapotide (NX-1207) BPH Extension Trial Successfully Meets Primary Endpoint

HOPE: Heart Outcomes Prevention Evaluation study

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

The IDEAL Study Reference

Diabetes Journal Club Julie Shah.

EVITA Trial design: Smokers admitted with an acute coronary syndrome were randomized to varenicline 1 mg twice daily (n = 151) vs. placebo (n = 151). Study.

SIGNIFY Trial design: Participants with stable coronary artery disease without clinical heart failure and resting heart rate >70 bpm were randomized to.

Late-Breaking Data on LDL-C Reduction

Presentation transcript:

A Placebo-Controlled Trial of Prucalopride for Severe Chronic Constipation Michael Camilleri, M.D., Rene Kerstens, M.Sc., An Rykx, Ph.D., and Lieve Vandeplassche, D.V.M., Ph.D. N Engl J Med 2008;358: R3. 조병현

Page  2  Constipation  15~50% of eldery(women>men)  a/w : infrequent bowel movement, hard stools, straining, bloating, feeling of incomplete evacuation after defecation  Mechanism : reduced colonic motility etc.  Prucalopride  selective, high-affinity 5-hydroxytryptamine4(5-HT4) receptor agonist  Increase colonic motility  decrease transit time  Other 5-HT4 receptor agonists  Interact in 5-HT3, 5-HT1b and hERG channel  an unfavorable cardiovascular profile and CNS symptoms Background aimed to determine the efficacy, safety, and effect on quality of life of 2-mg and 4-mg doses of oral prucalopride, given once daily for 12 weeks, in patients with severe chronic constipation

Page  3 Research Design and Method  Study - multicenter, randomized, double-blind, placebo-controlled, parallel-group  Patients - age : ≥18 years - chronic constipation :  two or fewer spontaneous, complete bowel movements per week for a minimum of 6 months

Page  4 Research Design and Method  Randomization - treatment period : 12wks - run-in phase : 2wks  two or fewer spontaneous, complete bowel movements per week - assigned consecutive numbers, starting with the lowest number - 3 groups : placebo, 2mg of prucalopride, 4mg of prucalopride - taken orally before breakfast  Disallowd medication - laxatives - except  3 or more consecutive days  15mg of bisacodyl  enema

Page  5 Research Design and Method  Assessments *Diaries Daily, timing, consistency, degree of straining, sensation of evacuation date & time of intake drug Primary efficacy– proportion of patients having 3 or more spontaneous, complete bowel movements per week during 12 weeks Secondary efficacy-proportion of patients with average increase of one or more spontaneous, complete bowel movements per week as compared with the baseline number *questionnaries PAC-SYM, PAC-QOL, SF-36 *Safety V/S, EKG, Lab tests, P/E,heart rate, QT interval

Page  6 RESULTS

Page  7 RESULTS

Page  8 RESULTS

Page  9 RESULTS

Page  10 RESULTS Serious adverse events 3 (1.4%) 7 (3.4%) 8 (3.8%) Lab abnormalities  no significant differences

Page  11 Conclusion  Over 12 weeks, prucalopride significantly improved bowel function and reduced the severity of symptoms in patients with severe chronic constipation.  Prucalopride given at a dose of 4 mg did not provide an incremental benefit over the 2 mg dose.  Larger and longer-term trials are required(to fully assess the risks and benefits).