Document 2868
 DOCN  M94A2868
 TI    The interim safety results and pharmacokinetics of a combination of
       R89439 and zidovudine therapy in HIV-infection.
 DT    9412
 AU    Colebunders R; Vandenbruaene M; Delescluse J; Vander Endt D; De Cree J;
       De Brabander M; Peeters M; Van den Broeck R; Stoffels P; Tropical
       Institute of Antwerp, Belgium.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):206 (abstract no. PB0252). Unique
       Identifier : AIDSLINE ICA10/94369707
 AB    R89439 (loviride) is the most potent product of the alpha-APA series (A
       group of Non Nucleoside Reverse Transcriptase Inhibitors) with an IC50
       of 1.7 ng/ml and good oral bioavailability (Cp at 8h = 130 ng/ml).
       OBJECTIVES: The objectives of the present trial were to document the
       possible pharmacokinetic interactions between loviride on zidovudine and
       to assess the safety of the combination therapy of loviride 50 mg or 100
       mg t.i.d. with zidovudine. METHODS: 18 patients were randomized in three
       groups of 6 patients in a double blind, double dummy placebo-controlled
       clinical trial. Patients received either loviride 100 mg t.i.d., 50 mg
       t.i.d. or placebo together with zidovudine. HIV1-positive patients with
       CD4 > 50 and < 350 CELLS/mm3 were eligible if they had taken zidovudine
       since more than 18 months. RESULTS: It was concluded that the
       pharmacokinetics of zidovudine were not affected by cotreatment with
       loviride 50 and 100 mg t.i.d. Sofar the codes have not been broken for
       the interim safety analysis. The incidence of adverse events was not
       significantly different between the three treatment groups, except for
       diarrhea which was only reported in one group. No clinically important
       laboratory changes were noted except for increased liver enzymes in one
       group, which progressively normalised after discontinuation of
       treatment. CONCLUSION: Adverse experiences although numerous were mostly
       mild to moderate. The complete safety and efficacy results will be
       reported at the conference.
 DE    Acetamides/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/
       PHARMACOKINETICS/*THERAPEUTIC USE  Acetophenones/ADMINISTRATION &
       DOSAGE/ADVERSE EFFECTS/  PHARMACOKINETICS/*THERAPEUTIC USE  Antiviral
       Agents/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/
       PHARMACOKINETICS/*THERAPEUTIC USE  Double-Blind Method  Drug
       Interactions  Human  HIV Infections/*DRUG THERAPY  Reverse
       Transcriptase/*ANTAGONISTS & INHIB  Safety  Treatment Outcome
       Zidovudine/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/
       PHARMACOKINETICS/*THERAPEUTIC USE  CLINICAL TRIAL  MEETING ABSTRACT
       RANDOMIZED CONTROLLED TRIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).