PHASE III PROTOCOL

Dr.RENJU.S.RAVI

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

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.

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

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.

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

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

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

“ 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.”

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

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

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.

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.

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

AIM:

To compare the efficacy and

safety of cardex vs nifedipine in patients

with stage I hypertension

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

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.

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

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)

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 .

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.

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)

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.

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

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.

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

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

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.

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.

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.

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:

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.

Patient with stage 1 HTN

Selection criteriaNot

satisfied

Out of

the studysatisfied

RCT

N=600 patientsNifedipine 20mg

N=300Cardex 10mg

N=300

Reduction in BP

Reduced platelet aggregation

Reduction in BP

Reduced platelet aggregation

Comparison of

outcome

conclusion

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

THANK YOU