Clinical trial NCT00002184: A Phase II, Stratified, Randomized, Double-Blind, Multi-Center Study of the Safety and Efficacy of Adefovir Dipivoxil (ADF) at Two Dose Levels in Triple Combination Therapies With Protease Inhibitors (PI) and Nucleoside Reverse Transcriptase Inhibitors (RTI) for the Treatment of HIV-Infected Patient
Official title: A Phase II, Stratified, Randomized, Double-Blind, Multi-Center Study of the Safety and Efficacy of Adefovir Dipivoxil (ADF) at Two Dose Levels in Triple Combination Therapies With Protease Inhibitors (PI) and Nucleoside Reverse Transcriptase Inhibitors (RTI) for the Treatment of HIV-Infected Patients With CD4 Cell Counts >= 100/mm3 and HIV-1 RNA Copy Numbers >= 5,000 Copies/Ml and Prior RTI Therapy But No Prior PI Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: HIV-1
Dose-Response Relationship, Drug
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
Zidovudine
Stavudine
HIV Protease Inhibitors
CD4 Lymphocyte Count
Lamivudine
RNA, Viral
Saquinavir
Nelfinavir
Reverse Transcriptase Inhibitors
Adenine
Anti-HIV Agents
Viral Load
Lead sponsor: NIH AIDS Clinical Trials Information Service
Sponsor class: INDUSTRY
First posted: 2001-08-31
Enrollment: 120
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and tolerance of the combination of adefovir dipivoxil at two comparative doses and nelfinavir plus saquinavir SGC administered orally (Group 1) vs. the combination of adefovir dipivoxil and nelfinavir plus either zidovudine, lamivudine, or stavudine (Group 2) vs. the combination of adefovir dipivoxil and saquinavir SGC plus either zidovudine, lamivudine, or stavudine (Group 3) in HIV-infected patients with prior nucleoside reverse transcriptase inhibitor therapy but no prior exposure to protease inhibitors who have CD4 cell counts \>= 100 cells/mm3 and an HIV-1 RNA baseline copy number \>= 5000 copies/ml. To determine the proportion of patients whose plasma HIV-1 RNA level falls below the level of detection (\<500 copies/ml) at 20 weeks of study therapy and the average reduction in HIV-1 RNA from baseline through study week 20. To evaluate the durability of the antiviral response through 48 weeks of study in patients who continue on study therapy after week 24.

Detailed description: This protocol is a stratified, randomized, double-blind, dose-comparative study of the safety and efficacy of adefovir dipivoxil in combination with nelfinavir and saquinavir soft gel capsules (SGC) or adefovir dipivoxil in combination with nelfinavir or saquinavir SGC plus a nucleoside analog (zidovudine, lamivudine, or stavudine).

Patients will be randomized to adefovir dipivoxil with nelfinavir and saquinavir or adefovir dipivoxil with nelfinavir or saquinavir plus a nucleoside analog (zidovudine, lamivudine, or stavudine). Within each treatment arm, patients will be randomized to 1 of 2 doses of adefovir dipivoxil in a blinded manner. Patients randomized to receive a nucleoside analog will then be assigned to receive either zidovudine, lamivudine, or stavudine based upon their previous RTI therapy. A daily dose of L-carnitine will be administered to all patients.

Eligibility criteria: Inclusion Criteria

Patients must have:

* Laboratory diagnosis of HIV infection (positive HIV antibody test confirmed by Western blot, p24 antigen assay, HIV-1 RNA, or HIV-1 culture).
* An HIV-1 RNA plasma titer \>= 5000 copies/ml within 14-21 days prior to the baseline visit.
* CD4 cell count \>= 100 cells/mm3 within 14-21 days prior to the baseline visit.
* A minimum life expectancy of at least 1 year.
* Signed, informed consent from parent or legal guardian for those patients \< 18 years of age.

Exclusion Criteria

Co-existing Condition:

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

* Active, serious infections (other than HIV infection) requiring parenteral antibiotic or antiviral therapy. Patients will be considered recovered from such infectious episodes if at least 2 weeks elapsed following the cessation of parenteral therapy before the baseline visit.
* Exhibiting evidence of a gastrointestinal malabsorption syndrome or chronic nausea or vomiting that may confer an inability to receive an orally administered medication.
* Malignancy other than cutaneous Kaposi's sarcoma (KS) or basal cell carcinoma. Patients with biopsy-confirmed cutaneous KS are eligible, but must not have received any systemic therapy for KS within 4 weeks prior to baseline and are not anticipated to require systemic therapy during the study.
* Any other clinical condition that in the opinion of the investigator would make the patient unsuitable for study or unable to comply with the dosing requirements.

Patients with any of the following prior conditions are excluded:

* A new AIDS-defining event diagnosed within 1 month prior to baseline.
* Significant history of peripheral neuropathy.

  1. Treatment with immunomodulating agents such as systemic corticosteroids, IL-2, or interferons.
* Ritonavir, indinavir, nevirapine, delavirdine, didanosine, dideoxycytidine, interferon alpha, interferon beta, isoniazid, rifampin, investigational agents (except upon Sponsor approval), chemotherapeutic agents (systemic), terfenadine, astemizole, cisapride, triazolam, and midazolam.

  1. Prior use of adefovir dipivoxil.
* Prior use of any antiretroviral protease inhibitor.
* Immunizations within 30 days of baseline.
* Antiretroviral vaccine therapy within 60 days of baseline.
* Treatment in the 4 weeks prior to baseline with immunomodulating agents such as systemic corticosteroids, IL-2, or interferons.
* Any other investigational drug within 30 days prior to baseline.
* Any prior therapy that, in the opinion of the investigator, would make the patient unsuitable for study or unable to comply with the dosing requirements.

Required:

Prior therapy for \> 4 weeks with any licensed nucleoside analog inhibitor of HIV reverse transcriptase.

Patients with current alcohol or substance abuse judged by the investigator to potentially interfere with patient compliance.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Body Positive
state: Arizona
city: Los Angeles
country: United States
facility: Krauss Med Partners / Dept of Research and Development
state: California
city: Los Angeles
country: United States
facility: UCLA Care Ctr
state: California
city: San Francisco
country: United States
facility: Davies Med Ctr
state: California
city: Greenwich
country: United States
facility: Blick Med Associates
state: Connecticut
city: Washington
country: United States
facility: George Washington Med Ctr
state: District of Columbia
city: Baltimore
country: United States
facility: Johns Hopkins Univ School of Medicine
state: Maryland
city: Worcester
country: United States
facility: Univ of Massachusetts Med Ctr
state: Massachusetts
city: Manhassett
country: United States
facility: North Shore Community Hosp
state: New York
city: Tulsa
country: United States
facility: Associates of Med and Mental Health
state: Oklahoma
city: Philadelphia
country: United States
facility: Univ of Pennsylvania
state: Pennsylvania
city: Pawtucket
country: United States
facility: Mem Hosp of Rhode Island
state: Rhode Island
city: Dallas
country: United States
facility: Univ of Texas Southwestern Med Ctr of Dallas
state: Texas
city: Ponce
country: Puerto Rico
facility: Hosp Regional de Ponce - Area Vieja
city: Santruce
country: Puerto Rico
facility: San Juan AIDS Program
Study officials:
References: