Study Methodology

Study Methodology

This study was a single-group, multiple-dose study of clinically relevant doses of OxyContin® in healthy adult volunteers. Subjects (see Table 1) were non-smoking, 18-50 years of age, with a body mass index between 18 and 32 kg/m2.

All participants were screened for phenotypic variation of the CYP2D6 enzymes using a commercially available screening test (PGXL Laboratories, Louisville, KY), and ultrarapid, rapid and poor metabolizers were excluded from the study. Other exclusions included individuals with histories of substance abuse, significant disease, recent illness, or abnormal findings on physical examination, electrocardiogram, laboratory studies or drug screens. Additionally, those with recent histories of prescription, over the counter and herbal drug use were excluded.

Thirty-six healthy volunteers (15 females and 21 males) each received naltrexone blockade throughout the study (50 mg daily naltrexone dosing initiated 12 hours before OxyContin® administration and continued through day 4) according to the study protocol.

The subjects were randomized to one of the three dosages of OxyContin®, 80, 160 or 240 mg/d dosed every 12 hours through day 4. On day 2, two presteady-state urine samples were collected every 12 hours. The half-life of OxyContin® is 4.5 hours, and most patients will reach steady state after 4-5 half lives of a drug, leaving most patients taking OxyContin® at steady state before day 3. Previous pharmacokinetic studies have confirmed that upon repeated doses of OxyContin®, patients achieve steady-state levels within 24-36 hours.1Beginning on day 3 at midnight, urine samples of all subjects were collected through 23:59 on day 4, while subjects were at steady state.

During this study, a total of 373 urine samples were collected while the subjects were in steady state for each dose of OxyContin®. In addition, pK blood and oral fluid samples were collected three times on days 3 and 4. Laboratory, medication, physical examination and adverse event findings were collected in the event of early termination or at the follow-up visit.

Table 1. Characteristics of study participants

Ameritox Table 1