Date: Wed, 12 Mar 97 17:10:32 EST From: "David Radune" Subject: New Information from ACTIS (03/12/97): NIAID ACTG 301 March 12, 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: NIAID ACTG 301. TITLE: A Phase II, Randomized, Double Blind, Placebo Controlled Trial of Memantine for AIDS Dementia Complex (ADC) As Concurrent Treatment with Antiretroviral Therapy. PHASE: Phase II. DISEASE STATUS: Patients must have the following symptoms and conditions: 1. HIV infection, as documented by any licensed ELISA test kit and confirmed by either Western blot, HIV culture, HIV antigen, plama HIV RNA or a second antibody test by a method other than ELISA at any time prior to study entry. 2. A diagnosis of AIDS dementia complex. PATIENT INCLUSION CRITERIA -------------------------- SPECIFICATION CRITERIA: Patients must have: 1. Documented HIV infection. 2. A diagnosis of AIDS dementia complex. 3. Estimated premorbid IQ of >= 70 consistent with completion of the 6th grade or the ability to read at a 6th grade level. 4. Impaired cognitive functioning. [Refer to Laboratory values for additional requirements.] AGE: 18 Years - 99 Years. SEX: M. F. REPRODUCTIVE SPECIFICATION: Not breast-feeding. Not pregnant. Negative pregnancy test within 14 days of study entry. PRIOR MEDICATION: Required: Concurrent treatment at a stable dose with any FDA approved antiretroviral therapy (e.g. nucleoside and/or protease inhibitors) alone or in combination for at least 8 consecutive weeks prior to study entry. CONCURRENT MEDICATION: Required: 1. Patients must be willing to maintain their antiretroviral regimen (whcih they have been on for at least 8 consecutive weeks prior to study entry) throughout the study. Allowed: 2. Prophylaxis for PCP. 3. Isoniazid. 4. Symptomatic therapies (such as analgesics, antihistamines, antiemetics, and antidiarrheal agents. 5. Maintenance or prophylactic therapy with clarithromycin, azithromycin, amikacin, ethambutol, clofazimine, ciprofloxacin, rifabutin, and rifampin for disseminated MAI. 6. Maintenance or prophylactic therapy with ganciclovir or foscarnet for CMV retinitis. Patients should be on a stable dose of ganciclovir or foscarnet for CMV retinitis for at least 1 month prior to study entry. 7. Patients taking anticonvulsants should have their anticonvulsant blood levels measured prior to starting medication and with changes in medication dosages. 8. Patients receiving stable doses of tricyclic antidepressants, serotonin-reuptake antagonists, or MAO inhibitors should be maintained on a stable dose level throughout the trial. Judicious use of benzodiazepines is also allowed. LABORATORY VALUES AT ENTRY -------------------------- HEMOGLOBIN: >= 9 g/dl. PLATELET COUNT: >= 50000 platelets/mm3. CD4 (T4 CELL) COUNT: Unspecified cells/mm3. SGPT (ALT): <= 5 X ULN. (ULN = Upper limit of normal) CREATININE: <= 2 X ULN. KARNOFSKY: >= 40. OTHER LABORATORY VALUES: Absolute neutrophil count >= 1000 cells/mm3. Alkaline phosphate <= 5 X ULN. Serum amylase <= 1.5 X ULN. If > 1.5 X ULN, then lipase or pancreatic amylase must be < 1.5 X ULN. PATIENT EXCLUSION CRITERIA -------------------------- SPECIFICATION CRITERIA: Patients with the following prior conditions are excluded: 1. Previous neurologic disease unrelated to HIV infection. 2. Previous chronic seizure disorders or head injuries (if the condition resulted in functional impairment or is likely to interfere with evaluations). 3. Previous central nervous system infections or neoplasms (such as toxoplasmosis, primary or metastatic CNS lymphoma, progressive multifocal leukoencephalopathy, cryptococcal or other fungal meningitis, tuberculous CNS infections and untreated neurosyphilis). [Refer to Laboratory values for additional requirements.] AGE: 01 Days - 17 Years. REPRODUCTIVE SPECIFICATION: Breast-feeding. Pregnant. Positive pregnancy test within 14 days of study entry. RISK BEHAVIOR: Excluded: Active alcohol or drug abuse which, in the investigator's opinion, is sufficient to prevent adequate compliance with study therapy and evaluations. PRIOR MEDICATION: Excluded: 1. Use of any investigational agent within 30 days prior to study entry. 2. Use of confounding NMDA antagonists (e.g. pentamidine if previously administered parenterally) or use of confounding calcium channel antagonists (to include nifedipine, verapamil, diltiazem, nimodipine, and related drugs) within 30 days prior to study entry. CONCURRENT MEDICATION: Excluded: 1. Systemic chemotherapy. 2. Use of confounding NMDA antagonists such as pentamidine (only if administered parenterally). 3. Use of phenothiazines or butyrophenones. 4. Use of confounding calcium channel antagonists (to include nifedipine, verapamil, diltiazem, nimodipine, and related drugs.) CO-EXISTING CONDITIONS OR DISEASES: Patients with the following conditions and symptoms are excluded: 1. Neoplasms other than basal cell carcinoma, in situ carcinoma of the cervix, or Kaposi's sarcoma without evidence of visceral involvement or which does not require systemic chemotherapy. 2. Any psychiatric illness which will confound the analysis of study endpoints. 3. Active symptomatic AIDS defining opportunistic infection. 4. Neurologic disease unrelated to HIV infection. 5. Chronic seizure disorders or head injuries if the condition results in functional impairment or is likely to interfere with evaluations. 6. Central nervous system infections or neoplasms (such as toxoplasmosis, primary or metastatic CNS lymphoma, progressive multifocal leukoencephalopathy, cryptococcal or other fungal meningitis, tuberculous CNS infections and untreated neurosyphilis). GENERIC DRUG NAME ----------------- Drug 1: Memantine. Antiparkinsonian. DRUG COMPANIES -------------- Drug 1: Neurobiological Technologies Incorporated 1387 Marina Way South Richmond, CA 94804 Contact: Dr Jeffrey S Price (510) 215-8000. END POINT --------- Efficacy. DISCONTINUE TREATMENT --------------------- Patients may be discontinued for any of the following reasons: 1. Unacceptable toxicity. 2. Patient has had study drug held for > 21 cumulative days on study. 3. The patient's ADC stage has worsened by >= 1 stage and he/she has been at MTD for >= 2 weeks. 4. Patient who misses consecutive clinic visits or fail to take study medications as prescribed without reasonable cause, as determined by the investigator. 5. Pregnancy or breast feeding. 6. Patient who requires systemic therapy for the treatment of a malignancy (other than Kaposi's sarcoma). 7. Patient who requires treatment with medications which are disallowed on study. 8. Patient has the right to withdraw from the study at any time for any reason. 9. The investigator has the right to remove patients from the study medications for clinical reasons which he/she believes are life threatening to the patient even if such reasons do not fall into the toxicity classification discussed above. 10. Development of a major opportunistic CNS complications. 11. Discontinuation of concomitant ZDV during study. 12. At the discretion of the ACTG, NIAID, FDA or pharmaceutical sponsor. PARTICIPATING UNITS ------------------- 0000003548: Queens Medical Center 1301 Punchbowl Street Honolulu, HI 96813-2499 Contact: Debra M. Ogata-Arakaki (808) 737-2751 OPEN 970129 ACTU: 5202. 0000001463: University of Hawaii / Leahi Hospital 3675 Kilauea Avenue / Young Building / 6th Floor Honolulu, HI 96816 Contact: Debra M Ogata-Arakaki (808) 737-2751 OPEN 970129 ACTU: 5201. 0000001349: Beth Israel Hospital / Massachusetts General Hospital 330 Brookline Avenue / Rose Building / Room 325 Boston, MA 02215 Contact: Sheila Hussey (617) 667-4103 OPEN 970213 ACTU: 0102. 0000001335: Washington University School of Medicine 4511 Forest Park / Suite 304 St Louis, MO 63108 Contact: Michael Klebert (314) 454-0058 OPEN 970218 ACTU: 2101. *****************************************************************