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

ViiV Healthcare

Status and phase: Completed; Phase 2

Conditions: HIV Infections

Treatments: Drug: Ritonavir; Drug: BMS-663068

Study type: Interventional

Funder types: Industry

Identifiers

NCT01009814

206267

AI438-006 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 50 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 5 patient groups

BMS-663068 600 mg Q12H + RTV 100 mg Q12H

Experimental group

Description:

All participants received BMS-663068 600 milligram (mg) and Ritonavir (RTV) 100 mg every 12 hours (Q12H) from Day 1 to Day 8.

Treatment:

Drug: Ritonavir

Drug: BMS-663068

BMS-663068 1200 mg QHS + RTV 100 mg QHS

Experimental group

Description:

All participants received BMS-663068 1200 mg and RTV 100 mg every night (quaque hora somni \[QHS\]) from Day 1 to Day 8.

Treatment:

Drug: Ritonavir

Drug: BMS-663068

BMS-663068 1200 mg Q12H + RTV 100 mg Q12H

Experimental group

Description:

All participants received BMS-663068 1200 mg and RTV 100 mg Q12H from Day 1 to Day 8.

Treatment:

Drug: Ritonavir

Drug: BMS-663068

BMS-663068 1200 mg Q12H + RTV 100 mg QAM

Experimental group

Description:

All participants received BMS-663068 1200 mg Q12H and RTV 100 mg every 24 hours in the morning (quaque ante meridiem \[QAM\]) from Day 1 to Day 8.

Treatment:

Drug: Ritonavir

Drug: BMS-663068

BMS-663068 1200 mg Q12H

Experimental group

Description:

All participants received BMS-663068 1200 mg Q12H from Day 1 to Day 8.

Treatment:

Drug: BMS-663068