AzTrials
AzTrials

HIV InfectionsPhase 1NCT00000742

A Phase I Concentration-Controlled Trial to Assess the Safety, Tolerance, Pharmacokinetics and Development of Decreased HIV-1 Susceptibility to the Combination of Atevirdine Mesylate (U-87201E), Zidovudine (AZT), and Didanosine (ddI)

A Phase 1 study testing Atevirdine mesylate, Zidovudine and Didanosine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Part I: To determine the pharmacokinetic dose for atevirdine mesylate ( U-87201E ) when used in combination with zidovudine ( AZT ). To determine the pharmacokinetic profiles of U-87201E and AZT over a 12-week period. Read more about this study

Who is it for?
Ages 13 years and older, men only
Conditions the study is for
HIV Infections
What is being tested?
Atevirdine mesylate, Zidovudine and Didanosine
How many people
15 participants
Where
5 sitesUnited States
Study dates
Start not givento Oct 1993
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 13 years and older
  • Men only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Concurrent Medication:
  • Allowed:
  • PCP prophylaxis with aerosolized pentamidine, trimethoprim / sulfamethoxazole or dapsone.
  • Clotrimazole troches or nystatin oral suspension for oral candidiasis.
  • Acyclovir (up to 1000 mg/day) for herpes lesions.
  • Patients must have:
Show all 10Show fewer
  • HIV infection documented by serologic tests or HIV culture OR prior diagnosis of AIDS by established CDC criteria.
  • CD4 counts = or < 500 cells/mm3 on two evaluations.
  • Part II only:
  • No prior therapy with antiretroviral or immunomodulating agents (e.g., AZT, ddI, ddC, interferon).

Who cannot join

  • Co-existing Condition:
  • Patients with the following symptoms and conditions are excluded:
  • Acute medical problems at time of study entry (including active opportunistic infections such as active cryptococcosis, Pneumocystis carinii, herpes zoster, histoplasmosis, or CMV, or nonopportunistic diseases including liver disease, renal disease, orthostatic hypotension, hypertension, lymphoma).
  • Current diagnosis of malignancy for which systemic therapy would be required during the study.
  • Concurrent Medication:
  • Excluded:
Show all 24Show fewer
  • Any other investigational drugs.
  • Phenobarbital, phenytoin, ketoconazole, rifampin, cimetidine, beta blockers, chronic anti-acid therapy, antiarrhythmic agents or other medications known to affect cardiac conduction or seizure threshold.
  • Cytotoxic chemotherapy.
  • Patients with the following prior conditions are excluded:
  • History of cardiovascular disease including conduction disturbances, arrhythmias, atherosclerotic heart disease, or valvular heart disease.
  • History of CNS disease such as seizure disorder, AIDS Dementia Complex, Progressive Multifocal Leukoencephalopathy, or any other active neurological disorder.
  • History of active or chronic gastrointestinal disorders such as chronic diarrhea (> 4 weeks duration), constipation, unexplained abdominal pain (such as irritable bowel syndrome), or other GI motility disorders.
  • History of hypercholesterolemia requiring medication or serum cholesterol = or > 300.
  • Part I patients only:
  • History of inability to tolerate zidovudine (200 mg q 8 hours).
  • Part III patients only:
  • History of pancreatitis or > grade 2 peripheral neuropathy.
  • Prior Medication:
  • Excluded:
  • Cytotoxic chemotherapy within 1 month prior to study entry.
  • Part II only:
  • prior therapy with antiretroviral or immunomodulatory agents (including but not limited to AZT, ddI, ddC, and interferon).
  • Current use of alcohol or illicit drugs.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • The Ohio State Univ. AIDS CRS

    Columbus, Ohio

  • USC CRS

    Los Angeles, California, 90033

  • Univ. of Miami AIDS CRS

    Miami, Florida

  • Univ. of Rochester ACTG CRS

    Rochester, New York, 14642

  • Washington U CRS

    St Louis, Missouri

Other trials in United States

About this study

Part I: To determine the pharmacokinetic dose for atevirdine mesylate ( U-87201E ) when used in combination with zidovudine ( AZT ). To determine the pharmacokinetic profiles of U-87201E and AZT over a 12-week period.

Part II: To determine whether or not decreased viral susceptibility to U-87201E develops when the drug is administered concomitantly with AZT for 12 weeks.

Read more

Part III: To evaluate the pharmacokinetic effects of ddI/AZT/U-87201E therapy and to assess changes in viral susceptibility to U-87201E.

Interest exists in the development of antiretroviral agents that possess different mechanisms of action from nucleoside analogs such as AZT. U-87201E is a non-nucleoside reverse transcriptase (RT) inhibitor that has demonstrated activity against HIV-1; however, an emerging characteristic of non-nucleoside RT inhibitors is the development of rapid resistance to HIV isolates. Whether this resistance can be prevented in the presence of nucleoside analogs such as AZT and ddI has yet to be determined.

Read the detailed description

Interest exists in the development of antiretroviral agents that possess different mechanisms of action from nucleoside analogs such as AZT. U-87201E is a non-nucleoside reverse transcriptase (RT) inhibitor that has demonstrated activity against HIV-1; however, an emerging characteristic of non-nucleoside RT inhibitors is the development of rapid resistance to HIV isolates. Whether this resistance can be prevented in the presence of nucleoside analogs such as AZT and ddI has yet to be determined.

Part I: Five male patients enter a pharmacokinetic concentration-controlled trial of U-87201E plus zidovudine at the University of Rochester site only. A target plasma concentration range at trough for U-87201E will be determined. Pharmacokinetic monitoring continues for 7 days or until the desired dose regimen has been determined. The five patients may be eligible to continue in Part II of the study to complete a total of 12 weeks of therapy.

Part II: At least 10 male patients (all sites eligible) in addition to the five patients from Part I receive doses of U-87201E as determined by Part I and AZT at the same dose as in Part I. Therapy is administered for 12 weeks. Patients with no decreased viral susceptibility to U-87201E after 6 weeks may be offered an extension to 24 or more weeks of therapy. Patients are followed weekly for 8 weeks and every other week thereafter until the end of the study.

Part III: At least eight patients who have received 24 weeks of U-87201E/AZT have ddI added to the regimen for 12 additional weeks.

Conditions
HIV Infections
Being tested
Atevirdine mesylate, Zidovudine, Didanosine
Keywords
Didanosine, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Antiviral Agents, Zidovudine
Medical subject headings
HIV Infections, Acquired Immunodeficiency Syndrome, AIDS-Related Complex

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Atevirdine mesylateDrug

  • ZidovudineDrug

  • DidanosineDrug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2001 (estimated)
  2. Study completionOct 1993

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Enrolment
15 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00000742
Sponsor's protocol ID
ACTG 199
Other IDs
11175
Status last verified
Oct 2021
First submitted
2 Nov 1999
Last updated
4 Nov 2021
Results posted
No

Publications

  • Reichman RC, Morse GD, Demeter LM, Resnick L, Bassiakos Y, Fischl M, Para M, Powderly W, Leedom J, Greisberger C, et al. Phase I study of atevirdine, a nonnucleoside reverse transcriptase inhibitor, in combination with zidovudine for human immunodeficiency virus type 1 infection. ACTG 199 Study Team. J Infect Dis. 1995 Feb;171(2):297-304. doi: 10.1093/infdis/171.2.297.

    PubMed 7531207

  • Morse G, Fischl M, Leedom J, Batts D, Cox S, Reichman R. Atevirdine (ATV) pharmacokinetics (PK) and dosage requirements during a concentration-targeted (CT) phase I study (ACTG 199). Int Conf AIDS. 1993 Jun 6-11;9(1):477 (abstract no PO-B26-2050)

  • Morse GD, Reichman RC, Fischl MA, Para M, Leedom J, Powderly W, Demeter LM, Resnick L, Bassiakos Y, Timpone J, Cox S, Batts D. Concentration-targeted phase I trials of atevirdine mesylate in patients with HIV infection: dosage requirements and pharmacokinetic studies. The ACTG 187 and 199 study teams. Antiviral Res. 2000 Jan;45(1):47-58. doi: 10.1016/s0166-3542(99)00073-x.

    PubMed 10774589

  • Reichman R, Fischl M, Para M, Powderly W, Timpone J, Bassiakos Y. Phase I study of atevirdine (ATV), a non-nucleoside reverse transcriptase inhibitor, given in combination with zidovudine (ZDV). The ACTG 199 Team. Int Conf AIDS. 1993 Jun 6-11;9(1):478 (abstract no PO-B26-2055)

  • Demeter LM, Resnick L, Tarpley WG, Fischl M, Para M, Reichman RC. Prolonged sensitivity of HIV-1 isolates to atevirdine (ATV) in a phase 1 clinical trial of ATV and zidovudine (ZDV) (ACTG 199). The ACTG 199 Study Team. Int Conf AIDS. 1993 Jun 6-11;9(1):242 (abstract no PO-A26-0643)

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Atevirdine mesylate, Zidovudine and Didanosine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00000742, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2021.

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