Document 2879
 DOCN  M94A2879
 TI    Phase I/II study of curdlan sulfate--an HIV inhibitor.
 DT    9412
 AU    Gordon M; Guralnik M; Lang W; Baker M; Goodgame J; DeMarzo C; Mimura T;
       Kaneko Y; AJI PHARMA USA, Inc., Glenpointe Centre West, Teaneck, NJ
       07666.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):204 (abstract no. PB0244). Unique
       Identifier : AIDSLINE ICA10/94369696
 AB    OBJECTIVE: To assess the safety, tolerance and pharmacokinetics of
       curdlan sulfate (CRDS), a semisynthetic beta-glucan, in HIV-positive
       individuals who have CD4 T-lymphocytes below 500 cells/cmm, administered
       as single doses over 30 minutes, or four hours, or daily for seven days.
       METHODS: CRDS was administered in separate studies to (1) three patients
       each at doses of 1, 10, 30, 100, 200 and 300 mg/70 kg infused over a 4
       hour period (2) two or three patients each at doses of 25, 50, 75, 100,
       125, 150, 175 and 200 mg/70 kg infused over 30 minutes (3) 3 patients
       each at doses of 40, 100, 140 and 180 mg/70 kg daily for 4 hours for 7
       days iv. Parameters measured were activated partial thromboplastin time
       (APTT), CD4, p24 antigen, chemistry and T-cell panels. RESULTS: CRDS has
       been found to be well tolerated at all doses. There were no clinical
       side effects or adverse changes in laboratory parameters other than the
       expected increase in APTT at higher doses, which reverted promptly to
       normal. Elevations in p24 antigen or drops in thrombocytes, previously
       seen with dextran sulfate, were not observed. At higher doses of CRDS
       marked unexpected increases in CD4 levels were observed which remained
       elevated for 4-24 hours. The half-life of CRDS was found to be 2-3
       hours. CONCLUSIONS: CRDS was well tolerated at all doses. If the marked
       increases in CD4 levels can be confirmed they may have therapeutic
       significance. Combination trials are recommended in HIV and in CMV
       disease.
 DE    Antiviral Agents/ADVERSE EFFECTS/PHARMACOKINETICS/*THERAPEUTIC  USE
       Glucans/ADVERSE EFFECTS/PHARMACOKINETICS/*THERAPEUTIC USE  Half-Life
       Human  Safety  Treatment Outcome  CLINICAL TRIAL  CLINICAL TRIAL, PHASE
       I  CLINICAL TRIAL, PHASE II  MEETING ABSTRACT

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