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Intravenous Safety and Pharmacokinetics of a Novel Dimerizer Drug, AP1903, in Healthy Volunteers

2001; Wiley; Volume: 41; Issue: 8 Linguagem: Inglês

10.1177/00912700122010771

1552-4604

John D. Iuliucci, Stuart Oliver, Steven K. Morley, Chris Ward, Janet Ward, David C. Dalgarno, Tim Clackson, Harvey J. Berger,

Virus-based gene therapy research

AP1903 is a novel gene‐targeted drug that is being developed for use in drug‐regulated cell therapies. An intravenous, single‐blind, placebo‐ and saline‐controlled, ascending‐dose study was performed to evaluate the safety, tolerability and pharmacokinetics of AP1903. Twenty‐eight normal healthy male volunteers were randomized into five dosage groups of AP1903 (0.01, 0.05, 0.1, 0.5, and 1 mg/kg). Within each group, 4 volunteers received a single dose of AP1903, 1 volunteer received an equal volume of placebo, and 1 received an equal volume of normal saline. The only exception was in the 0.5 mg/kg group, in which 4 volunteers were dosed: 3 received AP1903 and 1 received normal saline. All dosages were administered as intravenous infusions over 2 hours. Clinical safety parameters were monitored, and serial blood and urine samples were collected for analysis of AP1903. No drug‐related adverse events were observed at any of the dose levels with the possible exception of facial flushing in 1 volunteer at the 1.0 mg/kg dose level. AP1903 plasma levels were directly proportional to the administered dose, with mean C max values ranging from approximately 10 to 1275 ng/mL over the 0.01 to 1.0 mg/kg dose range. Following the infusion period, blood concentrations revealed a rapid distribution phase, with plasma levels being reduced to approximately 18%, 7%, and 1% of the maximal concentration at 0.5, 2, and 10 hours postdose, respectively. AP1903 was shown to be safe and well tolerated at all dose levels and demonstrated a favorable pharmacokinetic profile at doses well above the anticipated therapeutic dose .