Stimulation of cholecystokinin-A receptors with Gl181771X: a failed clinical trial that did not test the pharmacogenetic hypothesis for reduction of food intake.
There are two interacting components in a clinical trial: the drug and the study design. When a trial does not work, we blame the drug--and the study is usually not published. This Commentary provides a context for the use of efficacy pipeline pharmacogenetics (PGx) in therapeutic programs. Jordan et al. published the results of an obesity trial with a cholecystokinin-A (CCK-A) receptor agonist and concluded that CCK-A by itself does not have a central role in long-term energy balance. The conclusions were sound, the report accurate, and the journal commendable for publishing a negative study, but the trial design was misdirected--it did not build on phase IIA information and did not test the proposed mechanism of action. The hypotheses should have been based on the original putative role of a central mechanism affecting appetite, which had been validated using efficacy PGx in phase IIA.
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