Date: Mon, 10 Mar 97 16:08:40 EST From: "David Radune" Subject: New Information from ACTIS 03/10/97: FDA 244B & FDA 263A March 10, 1997 NEW INFORMATION FROM ACTIS The AIDS Clinical Trials Information Service (ACTIS) is a central resource providing current information on federally and privately sponsored clinical trials for AIDS patients and others infected with HIV. This service is a Public Health Service project produced collaboratively by the Centers for Disease Control and Prevention, the Food and Drug Administration, the National Institute of Allergy and Infectious Diseases, and the National Library of Medicine. NAC ONLINE, the computerized information service of the CDC National AIDS Clearinghouse, will alert you to any new information collected by ACTIS. A description of a recent clinical trial added to the ACTIS database is provided below. For more information, call the ACTIS toll-free number to talk with a health specialist. On request, you can also obtain a printout of a customized search of the clinical trials databases. The information can also be accessed directly by subscribers through two online databases, AIDSTRIALS and AIDSDRUGS, available through the National Library of Medicine. AIDS CLINICAL TRIALS INFORMATION SERVICE 1-800-TRIALS-A (1-800-874-2572) FAX: 1-301-738-6616 TTY/TDD: 1-800-243-7012 International Line: 1-301-217-0023 ***************************************************************** PROTOCOL NUMBER: FDA 244B. TITLE: A Randomized Double Blind Study of Safety, Virologic and Immunological Effects of Stavudine plus Lamivudine (3TC) Versus Zidovudine plus Lamivudine in HIV Infected Subjects Following At Least Six Months of Zidovudine Therapy. PHASE: Phase III. DISEASE STATUS: Patients must have the following symptoms and conditions: 1. At least six months of prior cumulative ZDV therapy. 2. Qualifying plasma HIV RNA count of >= 4 log10 copies/ml obtained within 2 weeks of randomization. PATIENT INCLUSION CRITERIA -------------------------- SPECIFICATION CRITERIA: Patients must have: 1. At least six months of prior cumulative ZDV therapy. 2. Qualifying plasma HIV RNA count of >= 4 log10 copies/ml obtained within 2 weeks of randomization. [Refer to Laboratory values for additional requirements.] AGE: 18 Years - 99 Years. SEX: M. F. REPRODUCTIVE SPECIFICATION: Not breast-feeding. Negative pregnancy test within 3 days prior to tudy entry. Not pregnant. Abstinence or effective method of birth control / contraception including oral contraceptives during the study. PRIOR MEDICATION: Required: At least 6 months of prior cumulative ZDV therapy. LABORATORY VALUES AT ENTRY -------------------------- HEMATOCRIT: >= 27 percent. (in the absence of blood transfusions or erythropoietin treatment in the preceding 2 weeks). HEMOGLOBIN: >= 9 g/dl. PLATELET COUNT: >= 75000 platelets/mm3. CD4 (T4 CELL) COUNT: Unspecified cells/mm3. SGOT (AST): <= 5 X ULN. (ULN = Upper limit of normal). SGPT (ALT): <= 5 X ULN. CREATININE: <= 1.5 X ULN. OTHER LABORATORY VALUES: Absolute neutrophil count >= 1000 cells/mm3 (in the absence of ongoing G-CSF or GM-CSF therapy). Total serum lipase <= 1.4 X ULN. HIV RNA count of >= 4 log10 copies/ml obtained within 14 days of randomization. PATIENT EXCLUSION CRITERIA -------------------------- SPECIFICATION CRITERIA: Patients with any of the following prior conditions or symptoms are excluded: 1. History of acute or chronic pancreatitis. 2. Prior history of bilateral peripheral neuropathy. 3. Intractable diarrhea (>= 6 loose stools/day for >= 7 consecutive days) within 30 days prior to study entry. [Refer to Laboratory values for additional requirements.] AGE: 01 Days - 17 Years. REPRODUCTIVE SPECIFICATION: Breast-feeding. Positive pregnancy test within 3 days prior to study entry. Pregnant. No abstinence or no agreement to use effective method of birth control / contraception during the study. RISK BEHAVIOR: Excluded: 1. Active alcohol abuse, sufficient in the investigator's opinion, to prevent compliance with study therapy or to increase the risk of developing pancreatitis. PRIOR MEDICATION: Excluded: 1. Any prior antiretroviral therapy except for ddI, ddC, 3TC or ZDV (for ZDV, as specified in inclusion criteria). 2. Previous therapy with agents with significant systemic myelosuppressive, neurotoxic pancreatotoxic, hepatotoxic or cytotoxic potential within 3 months of study start. 3. Therapy with rifampin, rifabutin, terfenadine, astemizole, cisapride, triazolam, midazolam and ketoconazole within 2 weeks prior to starting indinavir. 4. Any other prior therapy that, in the opinion of the investigator, would make the patient unsuitable for study or unable to comply with the dosing regimen. CONCURRENT MEDICATION: Excluded: 1. Therapy with agents with systemic myelosuppressive, neurotoxic pancreatotoxic, hepatotoxic or cytotoxic potential. 2. Therapy with rifampin, rifabutin, terfenadine, astemizole, cisapride, triazolam, midazolam and ketoconazole at any time while on indinavir therapy. CO-EXISTING CONDITIONS OR DISEASES: Patients with any of the following symptoms or conditions are excluded: 1. Presence of newly diagnosed AIDS defining opportunistic infection requiring acute therapy at time of enrollment. 2. Intractable diarrhea (>= 6 loose stools/day for >= 7 consecutive days). 3. Signs and symptoms of bilateral peripheral neuropathy >= grade 2 at the time of screening. 4. Inability to tolerate oral medication. 5. Any other clinical conditions that in the opinion of the investigator, would make the patient unsuitable for study or unable to comply with the dosing requirements. AVAILABILITY: Excluded: Patients who are not available for follow up for a period of 24 weeks. GENERIC DRUG NAME ----------------- Drug 1: Stavudine. Antiretroviral. Drug 2: Lamivudine. Antiretroviral. Drug 3: Zidovudine. Antiretroviral. Drug 4: Indinavir sulfate. Protease inhibitor. DRUG TRADE NAME --------------- Drug 1: d4T. Drug 2: 3TC. Drug 3: ZDV. DRUG COMPANIES -------------- Drug 1: Bristol - Myers Squibb Company PO Box 4500 Princeton, NJ 08543-4500 Contact: Drug Information (800) 662-7999. Drug 2: Glaxo Wellcome 5 Moore Drive / PO Box 13398 Research Triangle Park, NC 27709 Contact: Dept. of Consumer Affairs (800) 437-0992 X 7900. Drug 3: Glaxo Wellcome 5 Moore Drive / PO Box 13398 Research Triangle Park, NC 27709 Contact: Dept. of Consumer Affairs (800) 437-0992 X 7900. Drug 4: Glaxo Wellcome 5 Moore Drive / PO Box 13398 Research Triangle Park, NC 27709 Contact: Dept. of Consumer Affairs (800) 437-0992 X 7900. END POINT --------- Safety and efficacy. PARTICIPATING UNITS ------------------- 0000003695: Harbor UCLA Medical Center 1124 West Carson Street / Building N-24 Torrance, CA 90502 Contact: Crystal Lane (301) 222-3848 OPEN 970213. 0000002353: University of South Florida 12901 North 30th Street / Box 19 Tampa, FL 33612 Contact: Pat Seeley (813) 974-3163 OPEN 970213. 0000003843: SUNY at Stony Brook / Division of Infectious Diseases HSCT15 / Room 080 Stony Brook, NY 11794 Contact: Ruth Tenzler (516) 444-1658 OPEN 970213. 0000003840: University of Puerto Rico School of Medicine One Veterans Plaza (111) San Juan, PR 00927 Contact: Zydnia Pomales (787) 758-7575 X x5615 OPEN 970213. 0000003787: Houston Clinical Research Network / Div of Montrose Clinic 215 Westheimer Houston, TX 77006 Contact: Barbara Burkehart (713) 520-2000 OPEN 970213. 0000003841: University of Utah / School of Medicine / Div of Infect Dis 50 North Medical Drive / Room 2R002 Salt Lake City, UT 84132 Contact: Barbara Parchman - Wong (801) 581-4878 OPEN 970213. 0000003673: Montreal General Hospital / Div of Clin Immuno and Allergy 1650 Cedar Avenue / Room A5-140 Montreal / Quebec, CN H3G 1A4 Contact: Gretty Deutsch (514)934-8050 OPEN 970213. 0000003842: Sunnybrook Health Science Center 2075 Bayview Avenue / A226 North York / Ontario, CN M4N 3M5 Contact: Miriam Bast (416)480-6110 OPEN 970213. ***************************************************************** PROTOCOL NUMBER: FDA 263A. TITLE: A Phase I/II Trial to Evaluate the Tolerability, Anti-CMV Activity and Pharmacokinetics of 1263W94 Following Multiple Oral Administration of Escalating Doses in HIV Infected Patients with Asymptomatic CMV Shedding. PHASE: Phase I / Phase II. DISEASE STATUS: Patients must have the following symptoms and conditions: Required of Main group: 1. Minimum CMV titer of 5000 PFU/ml in semen by quantitative CMV culture on one occasion within 30 days of entry. 2. Demonstrating positive result of qualitative CMV culture in urine on one occasion within 30 days of entry. Required of Satellite group: 3. Must have CD4+ < 150 c/mm3 (or 10% of total lymphocytes) at screen. Required of both groups: 4. HIV infection. PATIENT INCLUSION CRITERIA -------------------------- SPECIFICATION CRITERIA: Patients must have: Required of Main group: 1. Minimum CMV titer of 5000 PFU/ml in semen by quantitative CMV culture on one occasion within 30 days of entry. 2. Demonstrating positive result of qualitative CMV culture in urine on one occasion within 30 days of entry. Required of Satellite group: 3. Must have CD4+ < 150 c/mm3 (or 10% of total lymphocytes) at screen. Required of both groups: 4. HIV infection. 5. Life expectancy > 6 months. 6. Able to comply with protocol requirements/instructions and likely to complete all study visits and evaluations as planned. [Refer to Laboratory values for additional requirements.] AGE: 18 Years - 99 Years. SEX: M. PRIOR MEDICATION: Allowed: Stable, chronically administered concommitant therapy for HIV infection and opportunistic diseases for at least one month prior. CONCURRENT MEDICATION: Allowed: Stable, chronically administered concommitant therapy for HIV infection and opportunistic diseases if patient has been on the regimen for at least one month prior to study entry. LABORATORY VALUES AT ENTRY -------------------------- HEMOGLOBIN: >= 8.5 g/dl. PLATELET COUNT: >= 50000 platelets/mm3. CD4 (T4 CELL) COUNT: < 150 cells/mm3. (0 - 100 - 150) (for Satellite group ONLY); Unspecified for maingroup. BILIRUBIN: <= 2 mg/dl. SGOT (AST): <= 4 X ULN. (ULN = Upper limit of normal). SGPT (ALT): <= 4 X ULN. CREATININE CLEARANCE: >= 50 ml/min. OTHER LABORATORY VALUES: Neutrophil count >= 750 c/mm3. PATIENT EXCLUSION CRITERIA -------------------------- SPECIFICATION CRITERIA: Patients with any of the following prior symptoms or conditions are excluded: 1. History of CMV disease (such as retinitis, colitis, encephalitis, pneumonitis, etc.) 2. Known history of lactose intolerance. [Refer to Laboratory values for additional requirements.] AGE: 01 Days - 12 Years. SEX: F. PRIOR TREATMENT: Excluded: 1. Treatment with radiation therapy for visceral malignancy within 2 months prior to entry. 2. Treatment with any investigational treatments within 1 month of study entry. CONCURRENT TREATMENT: Excluded: Treatment with radiation therapy for visceral malignancy. PRIOR MEDICATION: Excluded: 1. Systemic therapy for visceral malignancy within 2 months prior to entry. 2. Prior treatment with ganciclovir, foscarnet, cidofovir, or other investigational anti-CMV drugs (e.g. intravenous acyclovir, lobucavir, valaciclovir) within 2 months prior to entry. 3. Treated with interferons, immunomodulators or CMV hyperimmune globulin within 1 month prior to entry. 4. Any investigational therapies within 1 month prior of study entry. CONCURRENT MEDICATION: Excluded: Systemic therapy for visceral malignancy. CO-EXISTING CONDITIONS OR DISEASES: Patients with any of the following symptoms or conditions are excluded: 1. Active CMV disease (retinitis, colitis, encephalitis, pneumonitis, etc.). 2. Visual symptoms or signs suggestive of CMV disease (e.g. floaters, visual field defects, decreased visual acuity); Unless CMV disease is excluded via ophthalmoscopy examination. 3. Active hepatitis, obstructive hepatobiliary diseases or cirrhosis. 4. Gastrointestinal disorders which, in the judgement of the investigator, might interfere with oral dosing and drug absorption or may be indicative of CMV disease e.g., chronic nausea or vomiting, active bowel disease or persistent diarrhea. 5. Diagnosis of chronic diseases such as diabetes or hypoglycemia, epilepsy, ongoing Grade II peripheral neuropathy, congestive heart failure, cardiomyopathy, other organ dysfunctions, etc. which in the opinion of the investigator, would compromise the safety or compliance of the patient. 6. Participation in other investigational trials. 7. Patients who are so debilitated as a result of their HIV disease or associated illness or therapies such that, in the investigator's opinion, the condition may interfere with the study assessments or the patient's ability to complete the entire study per protocol requirements. GENERIC DRUG NAME ----------------- Drug 1: 1263W94. Antiviral. DRUG COMPANIES -------------- Drug 1: Glaxo Wellcome 5 Moore Drive / PO Box 13398 Research Triangle Park, NC 27709 Contact: Dept. of Consumer Affairs (800) 437-0992 X 7900. END POINT --------- Reduction of CMV titer in semen and if possible, reduction of semen CMV load in blood/plasma and urine. PARTICIPATING UNITS ------------------- 0000003833: University of California/ San Francisco / Dept of Medicine 995 Potrero Avenue / Ward 84 / Building 80 San Francisco, CA 94110 Contact: Mark Jacobson MD (415) 476-4082 X 407 OPEN 970212. 0000002423: Dr Jacob Lalezari 2300 Sutter Street / Suite 202 San Francisco, CA 94115 Contact: Dr Jacob Lalezari (415) 476-6356 OPEN 970212. *****************************************************************