Pharmacodynamics, Safety and Pharmacokinetics of BMS-663068, an HIV Attachment Inhibitor, in HIV-1
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: BMS-663068; Ritonavir
Intervention description: BMS-663068 will be administered as a tablet formulation; Ritonavir will be administered as a capsule.
Intervention MeSH terms: Ritonavir; Fostemsavir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV, HIV attachment inhibitor, attachment inhibitor

Summary:

      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.
    

Eligibility 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.