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E12A Principles for Clinical Evaluation of New Antihypertensive Drugs

DraftCenter for Drug Evaluation and Research08/09/2000
Good Clinical Practice

Description

This document provides general principles for the clinical evaluation of new anti- hypertensive drugs. It describes core principles for the evaluation of antihypertensives that are accepted in the three ICH regions, but some region-specific differences remain. These differences may be harmonized in future, but it is important  at present to refer to existing regional guidelines and to discuss the specific  requirements with regional regulatory authorities, if required.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

2
Antihypertensive Drugs

pediatric populations are on average less sensitive to these drugs

Fixed Combination Products

Specific category of antihypertensive products; products containing two or more antihypertensive agents

Stakeholders

4
Research Ethics Board

body to contact regarding research participant rights

Participant

A member of the clinical study population from whom data are being collected

Researcher

responsible for designing and executing the study

Regional Regulatory Authorities

entities to consult regarding fixed combination data requirements

Regulatory Context

Regulatory Activities

1
Clinical Evaluation

Process for assessing new antihypertensive drugs; the overall process of assessing new antihypertensive drugs

Document Types

1
Sample Consent Form

template provided for research study participation

Attributes

2
Dose-Response Relationship

Accurate dose-response information is important for maximizing desirable effects.

Fixed maintenance dose

The randomly assigned dose in a dose-response study

Technical Details

Substances

2
Placebo

Accountability procedures for the investigational product including placebo; used as a reference in a clinical trial

Active control drug

Alternative control for clinical study designs

Testing Methods

7
Factorial Study

using multiple doses of each component to show contribution; Comparing A plus B to A and to B at their highest approved doses

ABPM

Recommended Use of ABPM (Ambulatory Blood Pressure Monitoring); Abbreviation for ambulatory blood pressure monitoring

Randomized Withdrawal Study

used at the end of treatment to establish assay sensitivity

Single fixed-dose vs. placebo

Short-term study design for clinical evaluation

Optional titration

Study design based on response vs. Placebo

Forced titration

Study design vs. Placebo to reach maintenance dose

Fixed-dose, dose-response

Study design to evaluate dose-response relationship

Processes

1
Pharmacodynamic Studies

characterization of hemodynamic, renal, and neurohumoral effects

Clinical Concepts

7
Systolic Blood Pressure

Primary basis of assessment of efficacy; primary measurement for evaluating drug effect

Diastolic Blood Pressure

Primary basis of assessment of efficacy

Systolic Hypertension

Significant and remediable risk factor

Essential Hypertension

the primary condition for the study population

Orthostatic Hypotension

safety concern regarding excessive fall in blood pressure on standing

Target Organ Damage

secondary condition that limits inclusion in placebo-controlled trials

Short-term study designs

Appendix detailing clinical trial structures

Identified Hazards

Hazards

1
Cardiovascular Morbidity

potential detrimental effect requiring outcome studies

Standards & References

Specifications

2
Trough/Peak Ratio

evaluation of blood pressure control late in the dose interval

Assay Sensitivity

This stock can be used to determine the relative assay sensitivity for detecting RCR.

ICH References (10)

ICH E12A

Principles for Clinical Evaluation of New Antihypertensive Drugs

ICH E1

Regulatory standards for the extent of population exposure for treatments intended for long-term treatment

ICH E3

document remedial actions in the clinical trial report; Structure and Content of Clinical Study Reports standards.

ICH E4

Dose-Response Information to Support Drug Registration

ICH E5

Ethnic Factors in the Accessibility of Foreign Clinical Data.

ICH E6

Referenced for safety data collection and adverse event reporting plans.

ICH E7

Studies in Support of Special Populations: Geriatrics

ICH E8

General Considerations for Clinical Studies

ICH E9

Statistical Principles for Clinical Trials; Discourages deterministic procedures due to high risk of bias; Notes that the use of Bayesian methods in clinical trials may be considered.

ICH E10

Choice of Control Group in Clinical Trials.

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics

See Also (8)