Clinical Efficacy Testing for Orally Inhaled Drugs

1

• Clinical Efficacy Testing for Orally Inhaled
  Drugs
• Robert J. Meyer, MD
• Acting Director,
• DPDP

2
Introduction

• Observations About Inhaled Drugs
• Efficacy Determination for Inhaled Pulmonary
  Products
• Safety Determination for Inhaled Pulmonary
  Products

3
Clinically Characterizing Inhaled Drugs

• Intended Site of Action
• Locally Acting vs. Systemic
• Locally Acting
• Mechanism of Action
• Extent of Systemic Absorption
• Consequences of Systemic Absorption

4
Clinically Characterizing Inhaled Drugs

• For Locally Acting, Orally Inhaled Drugs
• Delivery to site of action cannot be inferred
  from serum pharmacokinetics
• Clinical Study Design Depend on Drug Class /
  Action
• Local safety (I.e., respiratory tract safety)
  cannot be inferred from PK
• Systemic safety may be approached by PK studies
  (depending on reference)

5
Clinically Characterizing Inhaled Drugs
Patient
Device
Drug
6
Clinically Comparing Inhaled Drugs

• Assuring equivalent delivery characteristics
  for efficacy does not fully address safety
• Assuring equivalent systemic delivery
  characteristic does not address relative efficacy
• In-vitro data, Scintigraphy data, PK data all
  useful in developing drugs, but not definitive
  for clinical characterization

7
Efficacy Testing of Inhaled Drugs

• Bronchodilators
• Direct Measures of Action
• Serial Spirometry (bronchodilation)
• Protection against bronchoprovocation
• Peak Flow Rate Assessments
• Supportive measures
• Symptoms and signs assessments

8
Efficacy Testing of Inhaled Drugs

• Corticosteroids
• Direct Measures of Action
• None
• Exploratory - eNO, airway inflammatory markers
• Indirect Measures of Action
• Serial Trough Spirometry
• Exacerbation rates / assessment of control
• symptoms / rescue use
• Protection against bronchoprovocation

9
Efficacy Testing of Inhaled Drugs

• Others - Cromolyn
• Direct Measures of Action
• ???
• Indirect measures of Action
• trough PFTs over time
• Symptoms / rescue use
• Protection against bronchoprovocation
• EIB, AMP,,

10
Safety Testing of Inhaled Drugs

• Tolerability of Drug Product
• Excipient issues
• Local safety
• Systemic safety
• PK useful, when possible and when well
  characterized reference exists
• If PK cannot be done, PD and AE assessments