Antimicrob Agents Chemother 1993 Mar;37(3):429-35

Biologic effects after a single dose of poly(I):poly(C12U) in healthy
volunteers.

Hendrix CW, Margolick JB, Petty BG, Markham RB, Nerhood L, Farzadegan H, Ts'o
PO, Lietman PS

Department of Medicine, School of Hygiene and Public Health, Johns Hopkins
University, Baltimore, Maryland 21205.

Poly(I):poly(C12U) (mismatched double-stranded RNA; atvogen), an interferon
inducer, is active against human immunodeficiency virus in vitro. To determine
the extent and duration of the biologic effects of poly(I):poly(C12U), we
administered a single dose of the drug to healthy volunteers in a randomized,
double-blind, placebo-controlled 2-week crossover study. We analyzed blood for
alpha and gamma interferons, neopterin, 2',5'-oligoadenylate synthetase,
lymphocyte surface markers, lymphocyte proliferation after exposure to soluble
antigens and mitogens, and natural killer cell activity. Minimal biologic
effects were observed after administration of a single 200-mg dose to four
volunteers; therefore, the dose was increased to 600 mg in 10 subjects. Only
neopterin levels and symptoms were greater after administration of 600 mg of
poly(I):poly(C12U) than after administration of placebo (Wilcoxon signed rank
sum test, P = 0.06). A definite response in 2',5'-oligoadenylate synthetase
activity, however, was seen in a few subjects. Neither alpha nor gamma
interferon was detectable in serum after poly(I):poly(C12U) dosing. The
neopterin changes after administration of poly(I):poly(C12U) were similar at
both poly(I):poly(C12U) dose levels, with an early decrease at 6 h, a peak at 1
day, and a gradual decrease toward the baseline over the following 3 days. A
mild flu-like syndrome occurred in one-half of the subjects following
administration of poly(I):poly(C12U) and in only one subject following
administration of placebo. This syndrome resolved within 16 h after
poly(I):poly(C12U) dosing.

Publication Types:
Clinical trial
Randomized controlled trial

PMID: 7681656, UI: 93213111