An Efficacy Study of 2',3'-Dideoxyinosine (ddI) (BMY-40900) Administered Orally Twice Daily to Zidovudine Intolerant Patients With AIDS or AIDS-Related Complex
3 other identifiers
interventional
660
2 countries
67
Brief Summary
AMENDED: 8/29/90 Inclusion of asymptomatic patients with CD4 counts less than 200 cells/mm3. Standardization of baseline evaluation schedule to allow 14 days prior to study dosing. Reduction in frequency and intensity of follow-up evaluations. Standardization of study endpoints. Inclusion of toxicity scoring and management for amylase and triglyceride elevations. Clarification of concomitant medication use. Original design: To determine the effectiveness of didanosine (ddI) in patients with AIDS or advanced AIDS related complex (ARC) who have documented hematologic intolerance to zidovudine (AZT) therapy. To determine if the efficacy of ddI increases with increasing doses. AZT is effective in reducing mortality in patients with AIDS who receive the drug after the first episode of Pneumocystis carinii pneumonia (PCP) and in patients with advanced ARC. However, AZT therapy has been associated with significant toxicities. In addition, the effectiveness of AZT appears to decrease during the second and third years of therapy. For these reasons, the development of alternative therapy that would be at least as effective but less toxic is of great importance. The drug ddI is an antiviral agent that inhibits replication (reproduction) of HIV with less apparent toxicity than AZT. The major dose-limiting toxicities found in the Phase I studies have been pains in the feet and legs of 2 patients initially receiving 12 mg/kg/day and 12 patients receiving daily doses of 25.8 to 51.2 mg/kg; symptoms began 8 to 27 weeks after initiating ddI treatment. These neuropathy-like symptoms have generally not been associated with significant abnormalities in nerve conduction studies and patients have reported marked improvement in symptoms within 1 to 2 weeks of discontinuing ddI. Some patients have resumed ddI treatment at a reduced dose after resolution of their symptoms. Studies indicate that ddI remains active in the body for at least 12 hours. This indicates that benefits of ddI might be achieved with a low frequency of drug administration.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 hiv-infections
67 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Primary Completion
Last participant's last visit for primary outcome
February 1, 1993
CompletedFirst Submitted
Initial submission to the registry
November 2, 1999
CompletedFirst Posted
Study publicly available on registry
August 31, 2001
CompletedMarch 14, 2011
October 1, 1994
November 2, 1999
March 11, 2011
Conditions
Keywords
Interventions
Eligibility Criteria
You may qualify if:
- Concurrent Medication:
- Required:
- Aerosolized pentamidine (300 mg every 4 weeks). In the event of physiological intolerance, alternative PCP prophylaxis may be trimethoprim/sulfamethoxazole 1 DS tab per day or dapsone 50 - 100 mg per day.
- Allowed:
- Chronic suppressive treatment for toxoplasmosis, Pneumocystis carinii pneumonia (PCP), cryptococcal meningitis, herpes simplex virus, cytomegalovirus, coccidioidomycosis, and histoplasmosis (absorption of ketoconazole or dapsone may be inhibited if given at the same time as the buffered solution of ddI, and should be taken 2 hours before or 2 hours after taking ddI; oral acidifying agents are not allowed). Isoniazid is permitted only if no acceptable alternative therapy is available. Metronidazole may be used for single courses not to exceed 14 days within consecutive 90 day intervals, the first of which begins at the initiation of the study. Erythropoietin for patients under the relevant treatment IND. Intravenous acyclovir for short courses of therapy.
- Patients must:
- Have documented hematologic intolerance to zidovudine (AZT).
- Have the diagnosis of AIDS or advanced AIDS related complex (ARC).
- Have ended treatment for acute Pneumocystis carinii pneumonia (PCP) at least 2 weeks before study entry.
- Have previous intolerance on at least two courses of AZT therapy (one of which must have been at daily doses of 500 mg of AZT or less).
- Be able to provide informed consent (and/or guardian as appropriate).
- Be available for follow-up for at least 6 months.
- Have baseline laboratory values as measured within 7 days before initial drug dosing.
- Allowed:
- Development of new opportunistic infections during the study - patients remain in the protocol.
- +5 more criteria
You may not qualify if:
- Co-existing Condition:
- Patients with the following are excluded:
- Presence of Kaposi's sarcoma (KS) with known or suspected visceral disease or where KS requires chemotherapy.
- Active AIDS defining opportunistic infections not specifically allowed.
- Intractable diarrhea.
- Stage 2 AIDS-dementia complex.
- History of intolerance to aerosolized pentamidine.
- Grade 2 neuropathy, based on the Neuropathy Targeted Symptom Questionnaire, or any moderate abnormality indicative of peripheral neuropathy, particularly impaired sensation of sharp pain, light touch, or vibration in the lower extremities, distal extremity weakness, or distal extremity hyporeflexia.
- Prior history of acute or chronic pancreatitis.
- History of seizures within past 2 years or currently requiring anticonvulsants for control.
- Any other clinical conditions or prior therapy which, in the opinion of the investigator, would make the patient unsuitable for study or unable to comply with the dosing requirements.
- Concurrent Medication:
- Excluded:
- Isoniazid (INH).
- Patients with the following are excluded:
- +28 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (67)
Los Angeles County - USC Med Ctr
Los Angeles, California, 90033, United States
Cedars Sinai / UCLA Med Ctr
Los Angeles, California, 900481804, United States
UCLA Med Ctr / Pediatric
Los Angeles, California, 900951752, United States
Harbor - UCLA Med Ctr / UCLA School of Medicine
Los Angeles, California, 905022004, United States
Palo Alto Veterans Adm Med Ctr / Stanford Univ
Palo Alto, California, 94304, United States
Univ of California / San Diego Treatment Ctr
San Diego, California, 921036325, United States
Stanford Univ School of Medicine
Stanford, California, 94305, United States
Olive View Med Ctr
Sylmar, California, 91342, United States
Sepulveda Veterans Adm Med Ctr / Olive View Med Ctr
Sylmar, California, 91342, United States
Harbor UCLA Med Ctr
Torrance, California, 90502, United States
Mountain States Regional Hemophilia Ctr / Univ of Colorado
Denver, Colorado, 80262, United States
Univ of Colorado Health Sciences Ctr
Denver, Colorado, 80262, United States
George Washington Univ Med Ctr
Washington D.C., District of Columbia, 20037, United States
G E Morey Jr
Fort Lauderdale, Florida, 33316, United States
Univ of Miami School of Medicine
Miami, Florida, 331361013, United States
Univ of South Florida
Tampa, Florida, 33612, United States
Northwestern Univ Med School
Chicago, Illinois, 60611, United States
Edward Hines Veterans Administration Hosp
Hines, Illinois, 60141, United States
Indiana Univ Hosp
Indianapolis, Indiana, 462025250, United States
Univ of Kansas School of Medicine
Wichita, Kansas, 67214, United States
Louisiana Comprehensive Hemophilia Care Ctr
New Orleans, Louisiana, 70112, United States
Louisiana State Univ Med Ctr / Tulane Med School
New Orleans, Louisiana, 70112, United States
Tulane Univ School of Medicine
New Orleans, Louisiana, 70112, United States
Johns Hopkins Hosp
Baltimore, Maryland, 21287, United States
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, 02114, United States
Boston Med Ctr
Boston, Massachusetts, 02118, United States
Beth Israel Deaconess - West Campus
Boston, Massachusetts, 02215, United States
Beth Israel Deaconess Med Ctr
Boston, Massachusetts, 02215, United States
Baystate Med Ctr of Springfield
Springfield, Massachusetts, 01199, United States
Med Ctr of Central Massachusetts
Worcester, Massachusetts, 01605, United States
Univ of Massachusetts Med Ctr
Worcester, Massachusetts, 01655, United States
Univ of Minnesota
Minneapolis, Minnesota, 55455, United States
Nebraska Regional Hemophilia Ctr
Omaha, Nebraska, 68105, United States
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, 14215, United States
City Hosp Ctr at Elmhurst / Mount Sinai Hosp
Elmhurst, New York, 11373, United States
Beth Israel Med Ctr / Peter Krueger Clinic
New York, New York, 10003, United States
Bellevue Hosp / New York Univ Med Ctr
New York, New York, 10016, United States
Mem Sloan - Kettering Cancer Ctr
New York, New York, 10021, United States
Saint Luke's - Roosevelt Hosp Ctr
New York, New York, 10025, United States
Mount Sinai Hemophilia Ctr / Mount Sinai Med Ctr
New York, New York, 10029, United States
Mount Sinai Med Ctr
New York, New York, 10029, United States
Univ of Rochester Medical Center
Rochester, New York, 14642, United States
SUNY - Stony Brook
Stony Brook, New York, 117948153, United States
SUNY / State Univ of New York
Syracuse, New York, 13210, United States
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
The Bronx, New York, 10461, United States
Jack Weiler Hosp / Bronx Municipal Hosp
The Bronx, New York, 10465, United States
Montefiore Med Ctr / Bronx Municipal Hosp
The Bronx, New York, 10467, United States
Bronx Veterans Administration / Mount Sinai Hosp
The Bronx, New York, 10468, United States
Univ of North Carolina
Chapel Hill, North Carolina, 275997215, United States
Duke Univ Med Ctr
Durham, North Carolina, 27710, United States
Bowman Gray School of Medicine / Wake Forest Univ
Winston-Salem, North Carolina, 27103, United States
Holmes Hosp / Univ of Cincinnati Med Ctr
Cincinnati, Ohio, 452670405, United States
Univ Hosp of Cleveland / Case Western Reserve Univ
Cleveland, Ohio, 44106, United States
Ohio State Univ Hosp Clinic
Columbus, Ohio, 432101228, United States
Milton S Hershey Med Ctr
Hershey, Pennsylvania, 170330850, United States
Univ of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Hemophilia Ctr of Western PA / Univ of Pittsburgh
Pittsburgh, Pennsylvania, 15219, United States
Univ of Pittsburgh Med School
Pittsburgh, Pennsylvania, United States
Julio Arroyo
West Columbia, South Carolina, 29169, United States
Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr
Knoxville, Tennessee, 37920, United States
Univ TX Galveston Med Branch
Galveston, Texas, 77550, United States
Hermann Hosp / Univ Texas Health Science Ctr
Houston, Texas, 77030, United States
Texas Children's Hosp / Baylor Univ
Houston, Texas, 77030, United States
Univ of Utah School of Medicine
Salt Lake City, Utah, 84132, United States
Univ of Washington
Seattle, Washington, 98105, United States
Great Lakes Hemophilia Foundation
Milwaukee, Wisconsin, 53233, United States
San Juan Veterans Administration Med Ctr
San Juan, 009275800, Puerto Rico
Related Publications (9)
Fichtenbaum CJ, Clifford DB, Powderly WG. Risk factors for dideoxynucleoside-induced toxic neuropathy in patients with the human immunodeficiency virus infection. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Oct 1;10(2):169-74. doi: 10.1097/00042560-199510020-00009.
PMID: 7552481BACKGROUNDKozal MJ, Kroodsma K, Winters MA, Shafer RW, Efron B, Katzenstein DA, Merigan TC. Didanosine resistance in HIV-infected patients switched from zidovudine to didanosine monotherapy. Ann Intern Med. 1994 Aug 15;121(4):263-8. doi: 10.7326/0003-4819-121-4-199408150-00005.
PMID: 7518658BACKGROUNDReddy MM, Winger EE, Hargrove D, McHugh T, McKinley GF, Grieco MH. An improved method for monitoring efficacy of anti-retroviral therapy in HIV-infected individuals: a highly sensitive HIV p24 antigen assay. J Clin Lab Anal. 1992;6(3):125-9. doi: 10.1002/jcla.1860060305.
PMID: 1506978BACKGROUNDGrieco MH, McKinley GF, Reddy MM. Effect of 2',3',-dideoxyinosine on HIV P24 antigen, beta2-microglobulin, neopterin,SCD8,SCD4,and SIL2R levels in patients with ARC or AIDS. Int Conf AIDS. 1991 Jun 16-21;7(2):199 (abstract no WB2069)
BACKGROUNDBozzette SA, Hays RD, Berry SH, Kanouse DE. A Perceived Health Index for use in persons with advanced HIV disease: derivation, reliability, and validity. Med Care. 1994 Jul;32(7):716-31. doi: 10.1097/00005650-199407000-00005.
PMID: 8028406BACKGROUNDFiscus SA, Heggem-Snow A, Troiani L, Wallmark E, Folds JD, Sheff B, van der Horst CM. Transient high titers of HIV-1 in plasma and progression of disease. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 May 1;9(1):51-7.
PMID: 7712235BACKGROUNDSpino C, Kahn JO, Dolin R, Phair JP. Predictors of survival in HIV-infected persons with 50 or fewer CD4 cells/mm3. J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Aug 15;15(5):346-55. doi: 10.1097/00042560-199708150-00004.
PMID: 9342254BACKGROUNDAllan JD, DeGruttola V, Cross A, McLaren C, Seidlin M, Pettinelli C. An efficacy study of 2'3'-dideoxyinosine [ddI](BMY-40900) administered orally twice daily to zidovudine intolerant patients with HIV infection (ACTG 118). The AIDS Clinical Trials Group. Int Conf AIDS. 1993 Jun 6-11;9(1):67 (abstract no WS-B24-2)
BACKGROUNDSharma PL, Chatis PA, Dogon AL, Mayers DL, McCutchan FE, Page C, Crumpacker CS. AZT-related mutation Lys70Arg in reverse transcriptase of human immunodeficiency virus type 1 confers decrease in susceptibility to ddATP in in vitro RT inhibition assay. Virology. 1996 Sep 15;223(2):365-9. doi: 10.1006/viro.1996.0488.
PMID: 8806572BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
JD Allan
- STUDY CHAIR
J Groopman
- STUDY CHAIR
M Seidlin