Phase 2 Safety and Efficacy Study of Bevirimat Functional Monotherapy in HIV Treatment-Experienced Patients for 2 Weeks*

This study has been completed.
Sponsor:
Information provided by:
Myrexis Inc.
ClinicalTrials.gov Identifier:
NCT00511368
First received: August 1, 2007
Last updated: January 15, 2010
Last verified: January 2010

August 1, 2007
January 15, 2010
April 2006
July 2008   (final data collection date for primary outcome measure)
HIV-1 RNA change from baseline over the first 14 days of study [ Time Frame: 14 days ] [ Designated as safety issue: No ]
HIV-1 RNA change from baseline over the first 14 days of study [ Time Frame: 14 days ]
Complete list of historical versions of study NCT00511368 on ClinicalTrials.gov Archive Site
safety and tolerability; pharmacokinetics [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
safety and tolerability; pharmacokinetics [ Time Frame: 14 days ]
Not Provided
Not Provided
 
Phase 2 Safety and Efficacy Study of Bevirimat Functional Monotherapy in HIV Treatment-Experienced Patients for 2 Weeks*
Phase 2 Dose-escalating, P-C, D-B, Parallel Group Study in HIV Treatment-experienced Patients to Evaluate the Safety, Tolerability and Efficacy of PA103001-04 Administered as Functional Monotherapy for 14 Days *(PART B)

The purpose of this study is to evaluate antiretroviral activity of up to five different oral doses administered for two weeks of bevirimat versus placebo in HIV treatment experienced patients, who have documented genotypic resistance to at least one major mutation from the IAS-USA list (2007)of resistance mutations for NRTIs, NNRTIs, or PIs. Patients will also be monitored for side effects, and the pharmacokinetics of bevirimat will be determined.

Bevirimat (PA103001-04) represents a new class of antivirals that blocks HIV replication by disrupting virus maturation; specifically, by inhibiting a late step in the Gag processing cascade. Short term (7-10 days) functional monotherapy studies (conducted in patients with detectable viral loads on a failing regimen)help in determining the potency of the drug, and enable dose finding. This is a two part (A and B)randomized, placebo-controlled, double-blind, multiple-dose, dose-escalation study in HIV treatment-experienced patients on a failing regimen (harboring resistance mutations to at least one member of the NRTI, NNRTI or PI classes. The antiretroviral activity, safety, and pharmacokinetics of up to 5 different dose levels of bevirimat will be compared to placebo when added to a failing approved antiretroviral regimen. The study is conducted in two parts: A and B. In Part A following 14 days of daily dosing patients commenced a new optimized ART regimen in addition to their randomized treatment. In Part Part B dosing with the randomized treatment ends after the initial 14 days of daily dosing.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
HIV Infections
  • Drug: matching placebo
    Other Names:
    • PA103001-04
    • PA-457N
  • Drug: Bevirimat
  • Placebo Comparator: 1
    placebo
    Intervention: Drug: matching placebo
  • Experimental: 2
    Bevirimat
    Interventions:
    • Drug: matching placebo
    • Drug: Bevirimat
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
92
July 2008
July 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male or female. Females of child-bearing potential, must have a documented negative pregnancy test and be willing to utilize double-barrier contraception through-out the study period.
  • Have HIV-1-infection.
  • Have a screening plasma HIV-1 RNA value, measured by the Roche Amplicor assay, of 2,000 - 250,000 copies/ml (inclusive).
  • Have documented evidence of genotypic resistance in their medical records (at screening) or have resistance at screening by genotype to any major mutation from the IAS-USA list of resistance drug mutations, defined as: NRTI resistance: M41L, K65R, D67N, K70R, K70E, L74V, Y115F, M184V, M184V/I, L210W, T215Y/F, K219Q/E; NNRTI resistance: L100I, K103N, V106M, V106A/M, V108I, Y181C, Y181C/I, Y188L, Y188C/L/H, G190S/A, G190A, P225H; Major PI resistance: D30N, V32I, L33F, M46I/L, I47V/A, G48V, I50L, I50V, I54M/L, L76V, V82A/F/T, V82A/F/T/S, V82L/T, I84V, N88S, L90M
  • Be receiving an antiretroviral therapy regimen containing at least 3 drugs (regimens containing ritonavir must not exceed a total daily dose of 400 mg) which has been unchanged for at least 8 weeks prior to initial screening.
  • Be able to receive an optimized background regimen.
  • Be free from any acute infection or serious medical illness within 14 days prior to study entry.
  • Be informed of the nature of the study and provide written informed consent.
  • Be willing to comply with the meal requirements described in the protocol.

Exclusion Criteria:

  • Current opportunistic infection characteristic of AIDS
  • Patients unable or unwilling to comply with the dosing schedule and protocol evaluations.
  • Patients with malabsorption syndromes affecting drug absorption.
  • Patients with systolic blood pressure < 90 mmHg or > 140 mmHg or diastolic blood pressure < 60 mmHg or > 90 mmHg measured in a semi-recumbent position after at least 10 minutes of rest at the screening or qualification visit.
  • A history of seizures (excluding pediatric febrile seizures), migraines, cluster and/or chronic headaches, cerebrovascular accident (CVA) or transient ischemic attacks (TIA).
  • Patients with abnormal Hemoglobin (< 10.0 g/dL for men and < 9.0 g/dL for women), Neutrophil count (< 1000/mm3), Platelet count (< 100,000/mm3), AST or ALT > 2.5 times the upper limit of normal (patients with a positive HBV surface antigen or HCV antibody test at screening must have AST and ALT no more than 1.5 times the upper limit of normal)
  • Patients who have received radiation therapy or cytotoxic chemotherapeutic agents, immunomodulating agents, HIV immunotherapeutic vaccine, an investigational drug or product, or participation in a drug study within 4 weeks prior to the first dose of study drug.
  • A history of alcoholism or drug addiction within the past 1 year (unless enrolled in a treatment program and approved by the sponsor). Recent use of any recreational drugs (except marijuana).
  • A history of difficulty donating blood or inadequate venous access.
  • The donation of blood or plasma within 30 days prior to receiving study medication.

Note: patients with a CD4 count <100 cells/mm3 will be considered for enrollment following discussion and agreement between the Investigator and the Sponsor.

Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00511368
PA103001-04 Study 203
Yes
Andrew Beelen, M.D, Sr. Director Clinical Research, Myriad Pharmaceuticals
Myrexis Inc.
Not Provided
Study Director: Andrew Beelen, M.D. Myrexis Inc.
Myrexis Inc.
January 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP