Integrating indacaterol dose selection in a clinical study in COPD using an adaptive seamless design

Area of Science:

• Pharmacology
• Clinical Trials
• Respiratory Medicine

Background:

• The drug development process traditionally separates dose-finding (Phase IIb) and efficacy/safety confirmation (Phase III).
• Adaptive seamless designs offer a streamlined approach by integrating these phases.
• This study investigated indacaterol, a once-daily inhaled long-acting beta(2)-adrenoreceptor agonist for COPD treatment, using this design.

Purpose of the Study:

• To evaluate the efficacy and safety of indacaterol in patients with moderate-to-severe COPD.
• To identify the optimal dose of indacaterol through an adaptive seamless trial design.
• To demonstrate the efficiency of adaptive seamless designs in drug development.

Main Methods:

• A 2-stage adaptive seamless clinical trial was conducted.
• The initial stage involved randomized treatment arms including various doses of indacaterol, formoterol, and tiotropium.
• Dose selection for the second stage was based on pre-set efficacy and safety criteria after 14 days of treatment.

Main Results:

• 801 patients with moderate-to-severe COPD were assessed.
• Indacaterol 150 microg was identified as the lowest effective dose, meeting efficacy criteria for bronchodilator effect.
• No safety concerns were observed for any indacaterol dose, leading to the selection of 150 microg and 300 microg for the second stage.

Conclusions:

• Adaptive seamless designs provide a novel and efficient method for combining dose selection with efficacy and safety evaluation in a single trial.
• This approach streamlines the clinical trial process for developing new COPD treatments.
• Indacaterol demonstrates promising efficacy and safety for COPD management.