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Phase 3 protocol

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Phase 3 protocol

  1. 1. PHASE III PROTOCOL Dr.RENJU.S.RAVI
  2. 2. PROTOCOL  It is a brief outline of what the study is & how it is to be carried out.  Main reference tool for the investigator  For submission to the Ethics committee to obtain permission to conduct the study 2
  3. 3. CLINICAL TRIALS  Clinical trials are studies performed with human subjects to test new drugs or combinations of drugs, new approaches to surgery or radiotherapy or procedures to improve the diagnosis of disease and the quality of life of the patient.
  4. 4. PHASES of Human research Phase I: Establish safety, PK studies Phase II : Establish efficacy,dose ranging Phase III : Randomized comparison of treatments Phase IV : Long term surveillance in broader population
  5. 5. Phase-III Clinical Trial  Multicentric study  Conducted by clinicians  Several hundred to few thousand patients  Lasts for 1 - 5 years  Study design-RCT  expensive, time-consuming and difficult trial to design.
  6. 6. Contd....... Document comparative efficacy and safety of new drug Document special characteristics of new drug Vs standard drug Determine optimum dosage schedule Document population kinetics if possible
  7. 7. Requirements - For permission to conduct phase III trial from DCGI 1. Introduction of drug 2. Chemical &Pharmaceutical information 3. Animal Pharmacology data 4. Details of Phase II Trial 5. Protocol of the proposed trial 6. Names& details of investigators 7. Details of institutions 8. Case report forms 9. Ethical clearance from IRB
  8. 8. Animal pharmacology data  Long term toxicity studies in animals  Three generation fertility studies  Peri/post natal studies in animals  Teratogenicity studies  Life span studies in mice and rats
  9. 9. “ Pharmaceutical company has marketed a novel CCB cardex for the treatment of mild to moderate essential hypertension. This drug has also been found to have additional antiplatelet property. You want to know whether it is safe and more efficacious than Nifedipine. Design a protocol for this study.”
  10. 10. Title A multicentric Parallel group double blind randomized control trial to compare the efficacy and safety of Cardex Vs Nifedipine in stage1 hypertension Protocol No: ASDW223 Version : 1.0 Date: 1/9/14 IND No: AK 0021
  11. 11. Chief Investigator: Dr. Ajay Assistant Professor, Dept of Internal Medicine MCH, Tvpm Phone: 9895005685 Co-investigator: Dr. Watson Assistant Professor, Dept of Internal Medicine MCH, Tvpm Phone: 9995678828 Sponsor: Glen mark Washington USA Ph :7680964765
  12. 12. INTRODUCTION Hypertension is one of the leading causes of morbidity and mortality in India. Chronic hypertension results in the development of coronary artery disease, cerebrovascular disease and end organ damage. Coronary artery disease is the most important long term complication of systemic hypertension. Patients are usually prescribed an antiplatelet drug like aspirin along with an antihypertensive like nicardipine to prevent re-occlusion.
  13. 13. Cardex is a novel calcium channel blocker with additional anti-platelet activity. Hence administering an antiplatelet drug separately is not required. In this context we are undertaking a study comparing the efficacy and safety of cardex with cardio selective CCB nifedipine.
  14. 14. Investigational product  Cardex is a novel calcium channel blocker with additional antiplatelet action. Phase I & Phase II trial has been done and data shows it is safe in humans.  Pharmacokinetic studies – A,D,M,E,Bioavailability  Pharmacodyanamic studies-receptor activity at cellular level
  15. 15. AIM: To compare the efficacy and safety of cardex vs nifedipine in patients with stage I hypertension
  16. 16. OBJECTIVES: Primary objective 1. To assess the efficacy and safety of cardex and its comparison with nifedipine in patients with stage I hypertension(JNCVIII) 2. To study the antiplatelet activity of cardex in patient with stage 1 HTN Secondary objective: 1. To study population kinetics
  17. 17. METHODOLOGY Study design: Double blind randomized control parallel group study to compare the efficacy and safety of cardex Vs Nifedipine Setting : Medicine OPD,MCH ,Tvpm. Total of 15 centers all over India Duration: 2 years Case definition: A case of stage I hypertension is a person having a BP greater than 140/90 mm hg but below 160/100 mm of Hg on three or more occasions.
  18. 18. Selection criteria  Inclusion criteria: a. Patients with newly diagnosed stage I hypertension acc. to JNC VIII b. Age group 20-65 yrs c. Patient not on any medications  Exclusion criteria a. Pregnant women b. Persons with hepatic or renal dysfunction c. severely ill patients d. Patients with bleeding disorders
  19. 19. Sample size: Total of 600 subjects. 300 in each arm Randomization : The study subjects are selected randomly using a computerized random table from newly diagnosed stage I hypertension patients attending the medicine OPD (Done from the trial Co-ordinator office)
  20. 20. Study Procedure  Selection of 600 Patients with with stage 1 hypertension Written informed consent obtained  Randomized to two groups of 300 each  Prior to the initiation of treatment, the systolic and diastolic BP will be assessed using syphgmomanometer .
  21. 21.  Base line investigations (Blood routine examination, LFT, RFT, lipid profile,Platelet count,BT,Platelet aggregation study, RBS) will be done in ACR lab, MCH Trivandrum  All relevant data will be recorded in prepared proforma.
  22. 22. Day 1  All 300 patients will receive cardex 10mg twice daily orally (after breakfast and after dinner)  The second group will receive nifedipine 20mg orally twice daily (after breakfast and after dinner)
  23. 23. Day 2  In all Patients BP measured in the morning at 8am after breakfast and morning dose of the drug  All the patients will be given tablets for the rest of the month to be taken at home  Asked to report any occurrence of side effects immediately to the investigators.
  24. 24. 2nd visit - At the end of one month • BP of all the patients will be recorded • 10 ml of blood - RBS, lipid profile,Platelet count,BT and platelet aggregation study. • If no significant side effect is noted the drugs will be given for a further period of 2 months • At the end of the period, patient will be asked to report for a third visit
  25. 25. 3rd visit  At the end of 3 months  BP of all patients will be recorded  10 ml of blood - estimate RBS, lipid profile Platelet count,BT and platelet aggregation study.  If no significant side effect is noted the drugs will be given for a further period of 3 months.
  26. 26. 4th visit • At the end of 6 months. • Recording of BP • RBS, lipid profile,BT, and platelet aggregation • If no significant side effect is noted the drugs will be given for a further period of 6 months
  27. 27. 5th visit • At the end of 12 months, final evaluation of the patients will be done. • Recording of BP • RBS, lipid profile,BT, and platelet aggregation 6th visit At the end of 18months • Follow up done up to 24 months
  28. 28.  All adverse effects during the period of study will be recorded in the adverse drug reaction form  If any serious ADE occurs it should be reported 1. within 24hrs to the sponsor 2. With in 7 days to the EC 3. With in 14 calendar days to the DCGI - expert committee. 30 days to decide upon compensation. Stopping rules  If patient develops any serious ADE  Drug should be stopped and appropriate treatment is started.
  29. 29. STATISTICAL ANALYSIS: • At the end of the study, BP during each of visits and platelet aggregatory studies will be evaluated. • SPSS version 16 will be used to evaluate the data. Student ‘t’ test and ANOVA will be used to estimate the significance.
  30. 30. ETHICAL ASPECTS  The study will be conducted acc to the declaration of Helsinki 2008,ICH& GCP guidelines . • After taking approval from the independent ethics committee, Medical College, Tvpm study will be started • A written informed consent will be obtained from all patients participating in the study.
  31. 31. INFORMED CONSENT  I.............hereby give my consent to be included as a subject in this study on “A multicentric parallel group double blind randomized control study to compare the efficacy and safety of Cardex Vs Nifedipine in Stage 1 Hypertension.” All the details regarding the study including any side effects and complications have been explained to me by Dr. Ajay , the principal investigator. I wholeheartedly agree without any compulsion to participate in this study. The principal investigator has explained to me that he will be collecting the data of my symptoms and results of blood tests & other investigations that has been done as part of the routine evaluation of my condition. The maintenance of confidentiality of the details has been assured. I am assured that I can withdraw from the study at any time and that my withdrawal from the study would not affect the treatment given to me.I also understand that there wouldn’t be any financial burden on me. Name of the investigator: Dr.Ajay Name of the patient: Signature and Date: Signature and Date: Name of the witness: Signature and Date:
  32. 32. OUTCOME • Mean reduction in systolic and diastolic BP by 10mmHg will be taken as the expected outcome. • A reduction in platelet aggregation as compared to initial value will be the 2nd expected outcome.
  33. 33. Patient with stage 1 HTN Selection criteria Not satisfied Out of the study satisfied RCT N=600 patients Nifedipine 20mg Cardex 10mg N=300 N=300 Reduction in BP Reduced platelet aggregation Reduction in BP Reduced platelet aggregation Comparison of outcome conclusion
  34. 34. REFERENCES 1. Cirzonna R, landmark L, frondoza GC. The new cardioselective calcium channel blocker-nifedipine a review. JAMA, 2005;8(2):125-32 2. Gupta S, Ravishankar G. A comparison of the antihypertensive effects of nicardipine with nifedipine.BMJ,2006;2(4):330-401. 3.Craig WA,Shaw WR,Ramgopal v Dhingra texbook ofHypertension and drug therapy fourth edition;32- 6:243-252
  35. 35. THANK YOU

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