According to FDA Draft Guidance published in March 2010, a pharmacokinetic (PK) study should be conducted in patients with impaired renal function when the drug is likely to be used in such patients and when renal impairment is likely to mechanistically alter the PK of the drug and/or its active metabolites. One example of this is if the drug or a principal active metabolite is eliminated renally. This is also a consideration if a drug is metabolized through the liver because renal impairment may inhibit certain pathways of hepatic and gut drug metabolism. As a result, a PK study in patients with renal impairment should be conducted for most drugs intended for use to treat chronic disease.
The study evaluated the tolerability, pharmacokinetic and pharmacodynamic effects of a treatment of secondary hyperparathyroidism after a single dose administration to patients with mild, moderate and severe renal impairment (not requiring dialysis), and a control group (age and gender matched normal healthy volunteers). The strategy was to evaluate the effect of the compound on an equal number of patients with different stages of impaired renal function.
A restrictive protocol made it difficult to recruit study volunteers; finding patients with moderate/severe renal impairment who met the strict inclusion/exclusion criteria of the study presented the major challenge to completing enrollment. Patients also needed to be confined for approximately 62 hours (or three nights) followed by three consecutive daily outpatient visits during the winter holiday period.