A Randomized, Double-Blind Study of MKC-442 Combined With Viracept in Patients Who Are Epivir + Retrovir Experienced and Are Protease Inhibitor- and Non-Nucleoside Reverse Transcriptase Inhibitor-Naive

This study has been completed.
Sponsor:
Information provided by:
NIH AIDS Clinical Trials Information Service
ClinicalTrials.gov Identifier:
NCT00002215
First received: November 2, 1999
Last updated: June 23, 2005
Last verified: April 1999
  Purpose

To compare the proportion of patients whose plasma HIV-1 RNA level falls and remains below the limit of quantification by the Roche Amplicor Monitor (400 copies/ml)[AS PER AMENDMENT 8/4/98: 50 copies/ml] between weeks 0 and 24. To determine the short-term safety and tolerability of MKC-442 plus nelfinavir (Viracept) plus dual nucleoside analogs. To determine the time to viral failure and time to tolerability failure through Week 48 of therapy.


Condition Intervention
HIV Infections
Drug: Emivirine
Drug: Nelfinavir mesylate

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind Study of MKC-442 Combined With Viracept in Patients Who Are Epivir + Retrovir Experienced and Are Protease Inhibitor- and Non-Nucleoside Reverse Transcriptase Inhibitor-Naive

Resource links provided by NLM:


Further study details as provided by NIH AIDS Clinical Trials Information Service:

Detailed Description:

In this randomized, placebo-controlled study, patients are allowed to switch at entry to d4T plus 3TC or d4T plus ddI based on investigator and patient preference. Patients are stratified based on the number of nucleoside reverse transcriptase inhibitor (NRTI) treatments that are changed at entry and on screening HIV-1 RNA (obtained within 30 days of entry) as follows: switched 1 NRTI and 10,000-50,000 copies/ml vs switched 1 NRTI and greater than 50,000 copies/ml vs switched 2 NRTIs and 10,000-50,000 copies/ml vs switched 2 NRTIs and greater than 50,000 copies/ml. Patients are randomized within each of these strata to 1 of the following treatment arms:

Arm 1: MKC-442 placebo plus nelfinavir. Arm 2: MKC-442 plus nelfinavir. Arm 3: MKC-442 plus nelfinavir (higher dose). Treatment is administered for 48 weeks. Patients who are considered virologic successes at Week 48 may continue to receive MKC-442 at the discretion of the investigator.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Required:

At least 1 different nucleoside analog, e.g., 3TC, d4T, or ddI (excluding zidovudine).

Allowed:

  • Chemoprophylaxis for Pneumocystis carinii pneumonia.
  • Short courses (less than 21 days) of acyclovir for acute treatment.
  • Recombinant erythropoietin or G-CSF for Grade 3 or greater anemia and neutropenia, respectively.
  • Allowed only with caution and close patient monitoring:
  • Ketoconazole, fluconazole, itraconazole, and grapefruit juice.
  • Medications metabolized by cytochrome P450.
  • Oral contraceptives, contraceptive implants such as Norplant, or injection-type contraceptives such as Depo-Provera only if not sole method of contraception.

Patients may have:

  • HIV-1 RNA greater than 10,000.
  • No active AIDS-defining illnesses.
  • Prior experience with 2 nucleoside analogues and able to switch to at least 1 different non-nucleoside analog, e.g., lamivudine (3TC), stavudine (d4T), or didanosine (ddI) with HIV-1 RNA 10,000 copies/ml or less. [AS PER:
  • 8/4/98 AMENDMENT].
  • [AS PER AMENDMENT 8/4/98:
  • Nucleoside analog-naive patients must have HIV-1 RNA greater than 50,000 copies/ml.].

Prior Medication:

Allowed:

Treatment with 2 nucleoside analogs. Note:

  • able to switch to at least 1 different nucleoside analog e.g., lamivudine (3TC), stavudine (d4T), or didanosine (ddI), while on study [AS PER AMENDMENT 8/4/98].

Exclusion Criteria

Co-existing Condition:

Patients with any of the following symptoms or conditions are excluded:

  • Active AIDS-defining illnesses.
  • Malabsorption syndrome or severe chronic diarrhea within 30 days of entry, or inability to consume adequate oral intake due to chronic nausea, emesis, or abdominal or esophageal discomfort. [AS PER AMENDMENT 8/4/98].
  • Inadequately controlled seizure disorder [AS PER AMENDMENT 8/4/98].
  • Any intercurrent illness that could affect viral load determination [AS PER AMENDMENT 8/4/98].

Concurrent Medication:

Excluded:

  • Zidovudine.
  • Immunomodulators (e.g., systemic corticosteroids, interleukin-2, or interferons). [AS PER AMENDMENT 8/4/98].
  • Rifampin, rifabutin, phenobarbital, and hydantoin.
  • Amiodarone, quinidine, astemizole, terfenadine, ergot derivatives, midazolam, triazolam, and cisapride.
  • Neurotoxic agents (e.g., vincristine, thalidomide). [AS PER AMENDMENT 8/4/98].

Patients with the following prior conditions are excluded:

  • History of acute or chronic pancreatitis.
  • History of > grade 2 peripheral neuropathy.
  • Patients with an acute and clinically significant medical event within 30 days of screening.

Prior Medication:

Excluded:

  • Protease inhibitors.
  • Non-nucleoside reverse transcriptase inhibitors.

Excluded within 30 days of study drug administration:

  • Immunomodulators (e.g., systemic corticosteroids, interleukin-2, or interferons). [AS PER AMENDMENT 8/4/98].
  • Rifampin, rifabutin, phenobarbital, and hydantoin.
  • Amiodarone, quinidine, astemizole, terfenadine, ergot derivatives, midazolam, triazolam, and cisapride.
  • Immunotherapeutic vaccines.
  • Cytotoxic chemotherapeutic agents [AS PER AMENDMENT 8/4/98].

Prior Treatment:

Excluded within 30 days of study drug administration:

Radiation therapy [AS PER AMENDMENT 8/4/98].

Risk Behavior:

Excluded:

Current alcohol or illicit drug use that, in the opinion of the investigator, may interfere with ability of patient to comply with dosing schedule and protocol evaluations.

  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: NCT00002215

Locations
United States, Pennsylvania
Anderson Clinical Research
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Triangle Pharmaceuticals
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00002215     History of Changes
Other Study ID Numbers: 292A, MKC-303
Study First Received: November 2, 1999
Last Updated: June 23, 2005
Health Authority: United States: Food and Drug Administration

Keywords provided by NIH AIDS Clinical Trials Information Service:
Drug Therapy, Combination
HIV Protease Inhibitors
RNA, Viral
Reverse Transcriptase Inhibitors
Viral Load
Nelfinavir
Uracil

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
HIV Protease Inhibitors
Nelfinavir
Protease Inhibitors
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014