PROTOCoL DESIGN

Importance

Protocol is the most important of all clinical trial documents

It is also the first to be prepared and discussed with the

investigators.

“ It is a confidential document since it contains information on drug “

Definition

A document that states the background, objectives, rationale, design,

methodology (including the methods for dealing with

AEs,withdrawals etc) and statistical considerations of the study. It

also states the conditions under which the study shall be performed

and managed.

Background

To study the effect of oral sulfonylurea in patient with type -2 diabetes

mellitus not previously treated with drug therapy.

Study Objectives

To assess the effectiveness of oral sulfonylurea in patients with type-2

diabetes diagnosed keeping in view that the patient is receiving

medication for the first time.

Study Design

Open Label,

Treatment (Glimepiride)

Active Control,

Safety/Efficacy Study

Diabetes Mellitus :

a group of diseases characterized by high levels of blood glucose

resulting from defects in insulin production, insulin action, or both

2 Types:

1) Type 1 diabetes

Insulin dependent diabetes

2) Type 2 diabetes

Non insulin dependent diabetes

blood glucose levels rise due to

1) Lack of insulin production

2) Insufficient insulin action

Sample Introduction

Glimepiride is a medium-to-long acting sulfonylurea anti-diabetic drug. It is

marketed as Amaryl by Sanofi-Aventis and Glyree by Ipca. Glimepiride is the first

third-generation sulfonylurea, and is very potent.

It is sometimes classified as third-generation, and sometimes classified as second-

generation.

Mechanism of action:

Pancreatic effect

Extra-pancreatic effect

Pancreatic effect:

Increase insulin release from pancreas

Suppress secretions of Glucagon

Extra pancreatic effect:

Increases the number of insulin receptors

Increases post-receptor insulin sensitivity

Increases glucolysis

Increases glycogen storage in muscle and liver

Decreases the hepatic output of glucose

Selection Criteria

Subjects already taking medication for type-2 diabetes mellitus:-No

Age eligible for study:-18Years to 40 Years

Genders eligible for study:-Both

Accepts healthy volunteers:-No

Inclusion criteria

Exclusion criteria

Withdrawal Criteria

Study Treatment

Life style modification

Diet control

All diabetic patients should be on diet control.

Diet control is a must either the patient is taking insulin

or oral therapy.

Over weight should be reduced .

Exercise

Smoking cessation

Insulin

Oral agents

Mechanism of action:

Pancreatic effect

Extra-pancreatic effect

Glimepiride 2mg per day

Once daily. Half-life 9 hours, peak action for 4 hours.

Phase/Type

Phase 2/Open Study

Patient

Type

Patients with type 2 diabetes not previously treated

with diet or oral drug

Trial Size Multicenter trial

Design Active control & openly treated with orally Glimepiride

drug

Dosing 2mg. Once Daily Glimepiride

Endpoints HbA1c, body weight, fasting plasma glucose, safety

Treatment of Type 2 Diabetes

Diagnosis

Therapeutic Lifestyle Change

After 12 Week check

Oral Drugs Only

Lab Test

Flow Chat

Lab Test Para Meter

Laboratory Examination

Glucose (Fasting)

Not lass than 120 mg/dl

Glucose (PP)

Not lass than 160 mg/dl

Glucose Torrance Test (GTT)

Hemoglobin (In Blood)

Not less than 8.0 gms/dl

HbA1C(Glycocyated

Hemoglobin)

Laboratory Examination

Urine(Rotten, Microscope)RM

Safety (Hepatic, CVD,

Hypoglycemia – While realizing that

diabetes is a serious disease!)

Efficacy (glycemic control, risk

factor reduction)

Side Effects (weight gain)

Patient acceptability

Preventing Diabetes

Complications

Glucose control

Blood pressure control

Blood lipid control

Preventive care practices for eyes,

kidneys, feet, teeth and gums

ADVERSE EVENTS (AE) REPORTING

Study Sponsor Notification by Investigator

A adverse event must be reported to the study sponsor by

telephone within 24 hours of the event. A Serious Adverse Event

(SAE) form must be completed by the investigator and faxed to the

study sponsor within 24 hours

EC/IRB Notification by Investigator

Reports of all adverse events (including follow-up information) must be

submitted to the EC/IRB within 10 working days.

FDA Notification by Sponsor

The study sponsor shall notify the FDA by telephone or by facsimile

transmission of any unexpected fatal or life-threatening experience

associated with the use of the drug as soon as possible but no later than 7

calendar days from the sponsor’s original receipt of the information.

Other Components

Quality control and assurance(QC/QA)procedures

Ethics( IDMC process, EC, Confidentiality)

Monitoring/ Direct access to data

Data Handling and record keeping

Financing and Insurance

Publication policy

Comparative approach

Regulatory Guidelines@

ICH-GCP

Indian GCP

Sch Y

Any Questions