A Phase I/II, Open Label Study to Evaluate the Antiviral Potential of Combination Zidovudine and 2' 3'-Dideoxyinosine (Didanosine) in Patients With Asymptomatic HIV Disease

NCT00000656 | Completed Phase 1

• 2 other identifiers: ACTG 14311118
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 5

Brief Summary

To assess the safety and to evaluate the anti-HIV effect of low-, moderate-, and high-dose schedules of zidovudine (AZT) plus didanosine (ddI) versus ddI alone in asymptomatic HIV-infected patients. Because of the failure with long-term (more than 1 year) use of, frequency of toxicity from, and drug resistance to AZT, drug combinations need to be developed to enable lower, less toxic doses of AZT to be used and to slow or prevent the development of resistance, while providing at least the same effectiveness.

Conditions

HIV Infections

Keywords

Didanosine; Drug Therapy, Combination; Zidovudine

Interventions

Zidovudine DRUG

Didanosine DRUG

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Concurrent Medication:
• Allowed:
• Aerosolized pentamidine.
• Acute and intermittent therapy with mycostatin and mycelex.
• Isoniazid, if no alternative therapy is available.
• Allowed for up to 2 weeks:
• Acyclovir for Herpes infection (withhold didanosine during therapy).
• Acute therapy with fluconazole or ketoconazole.
• Allowed but preferably not on a continuous basis for \> 72 hours:
• Acetaminophen.
• Ibuprofen.
• Nonsteroidal antiinflammatory agents.
• Patients must be:
• HIV antibody positive.
• Asymptomatic or have persistent generalized lymphadenopathy.

You may not qualify if:

• Co-existing Condition:
• Patients with the following conditions or symptoms are excluded:
• Unexplained temperature \> 38 degrees C for more than 5 consecutive days or on more than 10 days in any 30-day period in the 2 years prior to study entry.
• Unexplained diarrhea defined as at least 3 liquid stools/day persisting more than 7 days within 2 years prior to study entry.
• Unintentional weight loss of \> 10 pounds or \> 10 percent of usual body weight within 2 years prior to study entry.
• Oral hairy leukoplakia at any time prior to study entry.
• Recurrent oral candidiasis unrelated to the use of antibiotics within 2 years prior to entry or unrelated to the use of antibiotics within the past 3 months.
• Herpes zoster within 2 years prior to study entry.
• Seizures within the past 6 months or currently requiring anticonvulsants for control.
• Current heart disease.
• Current psychological or emotional problems sufficient in the investigator's opinion to prevent adequate compliance with study therapy.
• Gout.
• Concurrent Medication:
• Excluded:
• Rifampin.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Bristol-Myers Squibb: collaborator
• Glaxo Wellcome: collaborator

Study Sites (5)

Palo Alto Veterans Adm Med Ctr / Stanford Univ

Palo Alto, California, 94304, United States

Location

Whitman - Walker Clinic

Washington D.C., District of Columbia, 20009, United States

Location

Univ of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Univ of Pittsburgh Med School

Pittsburgh, Pennsylvania, United States

Location

Univ of Washington

Seattle, Washington, 981224304, United States

Location

Related Publications (9)

• Ragni MV, Amato DA, LoFaro ML, DeGruttola V, Van Der Horst C, Eyster ME, Kessler CM, Gjerset GF, Ho M, Parenti DM, et al. Randomized study of didanosine monotherapy and combination therapy with zidovudine in hemophilic and nonhemophilic subjects with asymptomatic human immunodeficiency virus-1 infection. AIDS Clinical Trial Groups. Blood. 1995 May 1;85(9):2337-46.

  PMID: 7727768 BACKGROUND

• Mamtora G, Winters M, Drenkow J, Shafer R, Shen N, Tran H, Merigan T, Gingeras T. HIV-1 GeneChip and dideoxynucleotide sequence analysis of HIV-1 genomes present in plasma samples from patients of ACTG 143 study. Int Conf AIDS. 1996 Jul 7-12;11(1):221 (abstract no TuA265)

  BACKGROUND

• Morse GD, Shelton MJ, Ho M, Bartos L, DeRemer M, Ragni M. Pharmacokinetics of zidovudine and didanosine during combination therapy. Antiviral Res. 1995 Aug;27(4):419-24. doi: 10.1016/0166-3542(95)00032-h.

  PMID: 8540760 BACKGROUND

• Kozal M, Winters M, Shafer R, Kroodsma K, Katzenstein D, Merigan T. Behavior of codon 74 and 215 pol gene mutations in 62 AZT experienced patients on ddI monotherapy. Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16:55

  BACKGROUND

• Fiscus SA, DeGruttola V, Gupta P, Katzenstein DA, Meyer WA 3rd, LoFaro ML, Katzman M, Ragni MV, Reichelderfer PS, Coombs RW. Human immunodeficiency virus type 1 quantitative cell microculture as a measure of antiviral efficacy in a multicenter clinical trial. J Infect Dis. 1995 Feb;171(2):305-11. doi: 10.1093/infdis/171.2.305.

  PMID: 7844365 BACKGROUND

• Winters MA, Shafer RW, Jellinger RA, Mamtora G, Gingeras T, Merigan TC. Human immunodeficiency virus type 1 reverse transcriptase genotype and drug susceptibility changes in infected individuals receiving dideoxyinosine monotherapy for 1 to 2 years. Antimicrob Agents Chemother. 1997 Apr;41(4):757-62. doi: 10.1128/AAC.41.4.757.

  PMID: 9087484 BACKGROUND

• Shafer RW, Iversen AK, Kozal MJ, Winters MA, Katzenstein DA, Merigan TC. HIV-1 (HIV) isolates resistant to both AZT and ddI developing in patients receiving combination therapy contain unique pol gene mutations. Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16:137

  BACKGROUND

• Holodniy M, Katzenstein D, Winters M, Montoya J, Shafer R, Kozal M, Ragni M, Merigan TC. Measurement of HIV virus load and genotypic resistance by gene amplification in asymptomatic subjects treated with combination therapy. J Acquir Immune Defic Syndr (1988). 1993 Apr;6(4):366-9.

  PMID: 8095981 BACKGROUND

• Shafer RW, Kozal MJ, Winters MA, Katzenstein DA, Ragni MV, Merigan TC. Combination therapy with ZDV+ddI suppresses virus load but does not prevent the emergence of HIV-1 isolates with ZDV resistance. ACTG 143 Protocol Virologists. Int Conf AIDS. 1993 Jun 6-11;9(1):68 (abstract no WS-B25-3)

  BACKGROUND

MeSH Terms

Conditions

HIV Infections

Interventions

Zidovudine; Didanosine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Inosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Ribonucleosides

Study Officials

• Ragni MV

  STUDY CHAIR

• Merigan TC

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: November 1, 1993
• Last Updated: November 3, 2021

Record last verified: 2021-10

Locations

US (5)