The Safety and Effectiveness of BI-RG-587 in HIV-Infected Patients

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Aug 30, 2001

Keywords

ClinConnect Summary

A compound free of the toxic effects of nucleoside chain terminators such as zidovudine (AZT) may have an advantage over currently available treatments for HIV infection. Such a compound has further advantages if it is active against AZT-resistant isolates. Nevirapine (BI-RG-587) has shown in vitro inhibitory activity against HIV-1 reverse transcriptase (RT). The molecular mechanism of the RT inhibitory effect is hypothesized to be non-competitive inhibition due to its binding to an RT site distinct from those for the RNA template primer, the deoxynucleotide triphosphate or the RNase H cata...

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ALL

Eligibility criteria

• • Inclusion Criteria
• Concurrent Medication:
• Allowed:
• • Pentamidine or dapsone prophylaxis for Pneumocystis carinii pneumonia (PCP) in patients with a CD4+ cell count = or \< 200 cells/mm3.
• • Antifungal prophylaxis with oral fluconazole or ketoconazole.
• • Antiviral prophylaxis with a maximum of 1 gram of oral acyclovir per day.
• • Acute therapy for intercurrent infections so long as that therapy is not an excluded medication of an excluded opportunistic infection.
• Patients must have:
• • Positive HIV antibody test results by ELISA.
• • Average of CD4+ cell count at 60 and at 21 days prior to study beginning = or \< 400 cells/mm3.
• • Seven of 10 patients in each treatment arm must have p24 antigen levels = or \> 70 pg/ml (\> 50 pg/ml at U. of Mass. site only) or be plasma viremic.
• • Preserved hematologic, hepatic, and renal function as defined by required lab values.
• • Ambulatory performance score of = or \> 70 Karnofsky.
• • Ability to voluntarily provide written informed consent prior to treatment.
• • Willingness and ability to follow protocol requirements.
• • Exclusion Criteria
• Co-existing Condition:
• Patients with the following symptoms or conditions are excluded:
• • Active cytomegalovirus disease.
• • Toxoplasmic encephalitis requiring suppressive therapy.
• • Mycobacteriosis requiring maintenance chemotherapy.
• • Visceral Kaposi's sarcoma requiring chemotherapy and/or irradiation.
• • Malignancy other than Kaposi's sarcoma or limited cutaneous basal cell carcinoma.
• • More than mild diarrhea (defined as more than transient or \> 4 loose stools per day).
• Concurrent Medication:
• The following medications / substances may NOT be ingested up to one hour before or 4 hours after a Nevirapine dose:
• • Antacids (particularly those containing calcium carbonate).
• • Cimetidine.
• • Carafate.
• • Cholestyramine resin.
• • Alcohol and alcohol-containing substances.
• • Benzodiazepines (diazepam, triazolam).
• Excluded:
• • Any approved or investigational antiretroviral, immunosuppressive, or cytotoxic drugs.
• • Glucocorticoids and steroid hormones (including oral contraceptives).
• • Dicumarol, warfarin, and other anticoagulant medications.
• • Nitroglycerin.
• • Digitoxin.
• • Valproic acid.
• • Tolbutamide.
• • Doxycycline.
• • Chloramphenicol.
• • Isoniazid.
• • Any sulfonamide medications.
• Patients with the following are excluded:
• • History of clinically important disease other than HIV infection defined by the investigator as possibly putting the patient at risk during study participation.
• • Conditions listed in Exclusion Co-Existing Conditions and symptoms.
• • Having received any approved or investigational antiretroviral, immunosuppressive, or cytotoxic drugs or any other experimental drug with 4 weeks of study entry.
• • A positive zidovudine (AZT) detection assay performed 7 days prior to drug dosing will exclude patients from study participation.
• Prior Medication:
• Excluded within 4 weeks of study entry:
• • Any approved or investigational antiretroviral, immunosuppressive or cytotoxic drugs.
• • Glucocorticoids and steroid hormones (including oral contraceptives).
• • Dicumarol, warfarin, and other anticoagulant drugs.
• • Nitroglycerin. Digitoxin.
• • Valproic acid.
• • Tolbutamide.
• • Doxycycline.
• • Chloramphenicol.
• • Isoniazid.
• • Antiepileptics (phenobarbital and other barbiturates).
• • Trimethoprim / sulfamethoxazole (Bactrim).
• Risk Behavior:
• Excluded:
• • Patients whose use of alcohol or drugs is sufficient to impair compliance with protocol requirements.