Pharmacodynamics, Safety and Pharmacokinetics of BMS-663068, an HIV Attachment Inhibitor, in HIV-1

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01009814
First received: November 6, 2009
Last updated: July 23, 2010
Last verified: July 2010
  Purpose

Research Hypothesis: Administration of BMS-663068, a prodrug for HIV attachment inhibitor BMS-626529, will result in a mean decrease of at least 1 log10 in HIV RNA at Day 9 following 8 days of therapy in at least one dosing regimen that is safe and well tolerated in Clade B HIV-1 infected subjects.


Condition Intervention Phase
HIV-1 Infections
Drug: BMS-663068 with or without ritonavir
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized, Open Label, Multiple-Dose Study to Evaluate the Pharmacodynamics, Safety and Pharmacokinetics of BMS-663068 in HIV-1 Infected Subjects

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Plasma HIV RNA levels (antiviral activity) [ Time Frame: Day 9 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • ECG, vital sign assessments, blood and urine samples for clinical laboratory evaluations [ Time Frame: 50 days after drug intake ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: November 2009
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
BMS-663068 and ritonavir
Drug: BMS-663068 with or without ritonavir

8-day treatment with BMS-663068 with or without ritonavir

Group 1: BMS-663068 600 mg Q12H + ritonavir 100 mg Q12H

Group 2: BMS-663068 1200 mg QHS + ritonavir 100 mg QHS

Group 3: BMS-663068 1200 mg Q12H + ritonavir100 mg Q12H

Group 4: BMS-663068 1200 mg Q12H + ritonavir 100 mg QAM

Group 5: BMS-663068 1200 mg Q12H

Experimental: Group 2
BMS-663068 and ritonavir
Drug: BMS-663068 with or without ritonavir

8-day treatment with BMS-663068 with or without ritonavir

Group 1: BMS-663068 600 mg Q12H + ritonavir 100 mg Q12H

Group 2: BMS-663068 1200 mg QHS + ritonavir 100 mg QHS

Group 3: BMS-663068 1200 mg Q12H + ritonavir100 mg Q12H

Group 4: BMS-663068 1200 mg Q12H + ritonavir 100 mg QAM

Group 5: BMS-663068 1200 mg Q12H

Experimental: Group 3
BMS-663068 and ritonavir
Drug: BMS-663068 with or without ritonavir

8-day treatment with BMS-663068 with or without ritonavir

Group 1: BMS-663068 600 mg Q12H + ritonavir 100 mg Q12H

Group 2: BMS-663068 1200 mg QHS + ritonavir 100 mg QHS

Group 3: BMS-663068 1200 mg Q12H + ritonavir100 mg Q12H

Group 4: BMS-663068 1200 mg Q12H + ritonavir 100 mg QAM

Group 5: BMS-663068 1200 mg Q12H

Experimental: Group 4
BMS-663068 and ritonavir
Drug: BMS-663068 with or without ritonavir

8-day treatment with BMS-663068 with or without ritonavir

Group 1: BMS-663068 600 mg Q12H + ritonavir 100 mg Q12H

Group 2: BMS-663068 1200 mg QHS + ritonavir 100 mg QHS

Group 3: BMS-663068 1200 mg Q12H + ritonavir100 mg Q12H

Group 4: BMS-663068 1200 mg Q12H + ritonavir 100 mg QAM

Group 5: BMS-663068 1200 mg Q12H

Experimental: Group 5
BMS-663068
Drug: BMS-663068 with or without ritonavir

8-day treatment with BMS-663068 with or without ritonavir

Group 1: BMS-663068 600 mg Q12H + ritonavir 100 mg Q12H

Group 2: BMS-663068 1200 mg QHS + ritonavir 100 mg QHS

Group 3: BMS-663068 1200 mg Q12H + ritonavir100 mg Q12H

Group 4: BMS-663068 1200 mg Q12H + ritonavir 100 mg QAM

Group 5: BMS-663068 1200 mg Q12H


  Eligibility

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

Inclusion Criteria:

  • Clade B HIV-1 infected subjects meeting following criteria at screening:

    • Plasma HIV RNA ≥ 5,000 copies/mL
    • CD4+ lymphocyte ≥ 200 cells/µL
    • Antiretroviral naive or experienced
    • Off all ARV therapy with HIV activity for > 8 weeks
  • BMI of 18 to 35 kg/m2, inclusive.
  • Not currently co-infected with HCV or HBV
  • Men and women, ≥ 18 years of age

Exclusion Criteria:

  • Woman of childbearing potential (WOCBP) unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period up to 12 weeks after the last dose of study drug.
  • WOCBP using prohibited contraceptive method including oral, injectable, or implantable hormonal contraceptive agent within 12 weeks of enrollment.
  • Women who are pregnant or breastfeeding.
  • Women with positive pregnancy test on enrollment or prior to study drug intake.
  • Sexually active fertile men not using effective birth control during study and for at least 12 weeks after last dose of study drug if partners are WOCBP.
  • Significant acute or chronic medical illness not stable or not controlled with medication or not consistent with HIV infection.
  • Current or recent (within 3 months) gastrointestinal disease that, in the opinion of Investigator or Medical Monitor, may impact on drug absorption and/or put subject at risk for GI tract irritation and/or bleeding.
  • Acute diarrhea lasting ≥ 1 day, within 3 weeks prior to randomization.
  • Major surgery within 4 weeks of study drug intake.
  • Gastrointestinal surgery that could impact upon absorption of study drug.
  • Donation of blood or plasma to blood bank or in a clinical study (except a Screening visit or follow up visit of less than 50 mL) within 4 weeks of study drug intake.
  • Blood transfusion within 4 weeks of study drug intake.
  • Inability to tolerate oral medication.
  • Inability to be venipunctured and/or tolerate venous access.
  • Personal history of clinically relevant cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for torsades de pointes.
  • Personal or family history of long QT syndrome.
  • Recent (within 6 months) drug/alcohol abuse
  • Any other medical, psychiatric and/or social reason which, in the opinion of the Investigator, would make the candidate inappropriate for participation.
  • Evidence of organ dysfunction or clinically significant deviation from normal in physical examination, vital signs, ECG or clinical lab determinations or not consistent with subject's degree of HIV infection.
  • Evidence of 2nd or 3rd degree heart block at screening or Day -1
  • Positive urine drug screen at Screening or Day -1 without valid prescription (subjects positive for cannabinoids and/or amphetamines will be included).
  • Positive blood screen for hepatitis B surface antigen.
  • Positive blood screen for hepatitis C antibody and hepatitis C RNA.
  • History of significant drug allergy
  • Exposure to any investigational drug or placebo within 4 weeks of study drug intake.
  • Prescription drugs within 4 weeks prior to study drug intake, unless approved by BMS medical monitor.
  • Other drugs, including over-the-counter medications, vitamins and/or herbal preparations, within 1 week prior to study drug intake, unless approved by BMS medical monitor.
  • Use of oral, injectable or implantable hormonal contraceptive agent within 12 weeks of study drug intake.
  • Use of prescription drugs or OTC drugs that may cause GI tract irritation or bleeding within 2 weeks of study drug intake, unless approved by BMS medical monitor.
  • Use of alcohol-containing beverages within 3 days prior to study drug intake.
  • Use of grapefruit,grapefruit-containing or Seville orange-containing products within 7 days prior to study drug intake.
  • Prisoners or subjects involuntarily incarcerated.
  • Subjects compulsorily detained for treatment of either a psychiatric or physical illness.
  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: NCT01009814

Locations
Germany
Local Institution
Berlin, Germany
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Study Director, Bristol Myers Squibb
ClinicalTrials.gov Identifier: NCT01009814     History of Changes
Other Study ID Numbers: AI438-006
Study First Received: November 6, 2009
Last Updated: July 23, 2010
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products

Keywords provided by Bristol-Myers Squibb:
HIV, HIV attachment inhibitor, attachment inhibitor

Additional relevant MeSH terms:
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014