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

This study has been completed.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Glaxo Wellcome
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000656
First received: November 2, 1999
Last updated: March 28, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Zidovudine
Drug: Didanosine
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 116
Study Completion Date: November 1993
Detailed Description:

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.

Enrollment during the first 8 weeks of the study is restricted to hemophiliacs and sexual partners of hemophiliacs with asymptomatic HIV disease. After the initial 8 weeks this restriction is lifted. Patients are randomized to one of four treatment arms with dosing of AZT plus ddI or ddI alone.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

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.
  • Diagnosed with one of the listed coagulopathies.
  • OR Sexual partner of someone with the above criteria.

Allowed:

  • Basal cell carcinoma or in situ carcinoma of the cervix.

NOTE:

  • As of January, 1991 full accrual of patients with prior AZT use has been reached - NOW ACCRUING ONLY THOSE WITH NO PRIOR AZT USE. Hemophilia restriction has been lifted.

Prior Medication:

Allowed:

  • Zidovudine (AZT) for a total of = or < 13 months.

NOTE:

  • As of January, 1991 accrual of these patients was reached, NOW ONLY PATIENTS WITH NO PRIOR AZT.

Exclusion Criteria

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.
  • Chemoprophylaxis for Pneumocystis carinii pneumonia other than aerosolized pentamidine.
  • Intravenous pentamidine.
  • Other antiretroviral agents, experimental medication, biological response modifiers, systemic corticosteroids, cimetidine, and ranitidine.
  • Barbiturates.
  • Oral acidifying agents.

Patients with a history of any of the following are excluded:

  • AIDS-defining opportunistic infection, advanced AIDS-related complex, or malignancy.
  • Acute or chronic pancreatitis.
  • Grade 2 or higher neuropathy based on the Neuropathy Targeted Symptom Questionnaire.
  • Seizures.
  • Zidovudine therapy for = or > 13 months.
  • Heart disease.
  • Psychological or emotional problems sufficient in the investigator's opinion to prevent adequate compliance with study therapy.
  • Gout.

Prior Medication:

Excluded within 4 weeks of study entry:

  • Antiretroviral agents, including ribavirin, HPA-23, rifampin, AL721.
  • Excluded within 3 months of study entry:
  • Significant course of immunomodulating agents, such as steroids (> 1 week), isoprinosine, thymic factors, or any other experimental drugs.
  • Excluded within 30 days prior to study entry:
  • Neurotoxic drugs.

Excluded:

  • Didanosine (ddI).
  • Dideoxycytidine (ddC).
  • Zidovudine (AZT) if received for > 13 months.

Prior Treatment:

Excluded within 3 months of entry:

  • Other experimental therapy.

History of recent alcohol abuse.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000656

Locations
United States, California
Palo Alto Veterans Adm Med Ctr / Stanford Univ
Palo Alto, California, United States, 94304
United States, District of Columbia
Whitman - Walker Clinic
Washington, District of Columbia, United States, 20009
United States, Pennsylvania
Univ of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Univ of Pittsburgh Med School
Pittsburgh, Pennsylvania, United States
United States, Washington
Univ of Washington
Seattle, Washington, United States, 981224304
Sponsors and Collaborators
Bristol-Myers Squibb
Glaxo Wellcome
Investigators
Study Chair: Ragni MV
Study Chair: Merigan TC
  More Information

Additional Information:
Publications:
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)
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
Morse GD, Ragni M, Bartos L, Ho M. Pharmacokinetics of zidovudine and didanosine during combination therapy in ACTG Protocol 143. Int Conf AIDS. 1992 Jul 19-24;8(2):B186 (abstract no PoB 3596)
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
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)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000656     History of Changes
Other Study ID Numbers: ACTG 143, 11118
Study First Received: November 2, 1999
Last Updated: March 28, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Didanosine
Drug Therapy, Combination
Zidovudine

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Didanosine
Zidovudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014