Research Design Considerations for Single-Dose Analgesic Clinical Trials in Acute Pain

This webinar will review the recent article in Pain by Cooper et al that summarizes the findings of a meeting convened by IMMPACT, the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials. The article looked at key considerations and best practices governing design of acute pain studies. A single-dose analgesic study is usually the first step in a clinical development plan to establish the safety and efficacy for an acute pain medication. This first study should be conducted in an established postsurgical model to determine proof of concept, the effective dose range, analgesic properties such as time to onset of analgesic activity, magnitude of analgesic activity, and duration of analgesic effect. The relationship between dose and efficacy/safety also can be defined. Inclusion of a placebo arm allows for determination of the treatment effect and relative safety versus an untreated population. A positive control arm provides validation of the model, and relative potency against an established analgesic medication also can be determined.

Importance of preclinical research

Data derived from preclinical in vitro studies and in vivo animal models can provide important guidance on designing the clinical development plan. Determination of receptor binding characteristics, mechanism of action, whether the drug has central or peripheral nervous system activity, the metabolic profile, and the degree of protein binding can provide clues regarding the appropriate clinical models and study designs.

Key elements to consider in every acute pain analgesic study are:

Efficacy and safety in acute pain models. Fully characterizing these factors is essential to any analgesic trial. Efficacy attributes include onset of effect, maximum analgesic effect and duration of effect, and overall effect across the dosing interval. It’s also important to characterize the full adverse effect profile.

General research design considerations. A placebo treatment arm and a positive control arm are highly recommended.

Proof of concept and dose ranging. The initial proof-of-concept study should define the dose-response relationship, and comparator analgesics should be used as benchmarks for judging assay sensitivity and the relative efficacy of the investigational compound.

Choosing the right active comparator. In the absence of established standards, it’s wise to choose comparators whose mechanism of action is similar to the treatment under study.

The major efficacy domains in acute pain trials are pain intensity and pain relief. Additionally, analgesic onset and duration are important measures in most conditions. The webinar also will address documentation and reporting of adverse events and conclude with 10 best practices and principles that should be factored into every acute pain analgesia trial as recommended by the IMMPACT group.

Join us in exploring the current state of knowledge and experience for evaluating the efficacy and safety of medications that treat acute pain.

Speaker

Michael Kuss, Vice President, Analgesia, Premier Research

Michael Kuss, Vice President, Analgesia, Premier Research

Michael Kuss leads a highly experienced group of researchers who provide sponsors with clean data that can confidently be used to support marketing for their drugs in development. Premier Research has developed multiple proprietary pain models that minimize the variability of subjective responses to pain and that have become industry standards for analgesia research.

Mr. Kuss is responsible for the company’s analgesia franchise and providing strategic analgesic drug development services to sponsors. He also serves as a consultant for external and internal customers with regard to operational execution of analgesic clinical study protocols. Prior to joining Premier Research in 2001, he worked at Pharmacia (GD Searle and Monsanto), where he was involved in the clinical development of several NSAIDs and COX-2 inhibitors as part of the Arthritis, Inflammation, and Pain team. He also worked as a clinical research associate at Abbott Laboratories.

He holds a bachelor’s degree in medical technology from Wright State University in Dayton, Ohio.

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