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Clinical Trials/NCT01009814
NCT01009814CompletedPhase 2

Randomized, Open Label, Multiple-Dose Study to Evaluate the Pharmacodynamics, Safety and Pharmacokinetics of BMS-663068 in HIV-1 Infected Subjects

ViiV Healthcare1 site in 1 country50 target enrollmentStarted: November 23, 2009Last updated:
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Conditions
Interventions
Drugs

Trial Snapshot

Phase
Phase 2
Status
Completed
Enrollment
50
Locations
1
Primary Endpoint
Mean Logarithm With Base 10 (Log10) Change From Baseline in Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) at Day 9
Study OverviewStudy DesignEligibility CriteriaArms & InterventionsOutcomesInvestigatorsSitesRecords & IdentifiersSimilar Trials

Study Overview

Brief 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.

Study Design

Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel
Primary Purpose
Treatment
Masking
None

Eligibility Criteria

Ages
18 Years to — (Adult, Older Adult)
Sex
All
Accepts Healthy Volunteers
No

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.

Arms & Interventions

BMS-663068 600 mg Q12H + RTV 100 mg Q12H

Experimental

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

Intervention: BMS-663068 (Drug)

BMS-663068 600 mg Q12H + RTV 100 mg Q12H

Experimental

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

Intervention: Ritonavir (Drug)

BMS-663068 1200 mg QHS + RTV 100 mg QHS

Experimental

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

Intervention: BMS-663068 (Drug)

BMS-663068 1200 mg QHS + RTV 100 mg QHS

Experimental

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

Intervention: Ritonavir (Drug)

BMS-663068 1200 mg Q12H + RTV 100 mg Q12H

Experimental

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

Intervention: BMS-663068 (Drug)

BMS-663068 1200 mg Q12H + RTV 100 mg Q12H

Experimental

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

Intervention: Ritonavir (Drug)

BMS-663068 1200 mg Q12H + RTV 100 mg QAM

Experimental

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.

Intervention: BMS-663068 (Drug)

BMS-663068 1200 mg Q12H + RTV 100 mg QAM

Experimental

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.

Intervention: Ritonavir (Drug)

BMS-663068 1200 mg Q12H

Experimental

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

Intervention: BMS-663068 (Drug)

Outcomes

Primary Outcomes

Mean Logarithm With Base 10 (Log10) Change From Baseline in Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) at Day 9

Time Frame: Baseline and Day 9

The primary assessment of the antiviral activity of BMS-663068 was assessed on the log10 change from Baseline in HIV RNA to Day 9. Baseline was the last non-missing observation before first dose (Day 1 pre-dose) and change from Baseline was calculated by subtracting Baseline value from post-Baseline visit value. An analysis of covariance (ANCOVA) model correcting for Baseline HIV viral load and treatment group was used to test the differences in mean log10 decrease in HIV RNA at Day 9 between 2 regimen groups by antiretroviral treatment history (ARV \[antiretroviral\] naive, ARV experienced, and combined \[ARV naive + ARV experienced\]). For the combined group (ARV naive +ARV experienced) an additional ANCOVA was used correcting also for treatment history as an additional covariate. Only Clade B participants were included in the population.

Secondary Outcomes

  • Change From Baseline in Cluster of Differentiation 4 Positive (CD4+) Cell Count and Cluster of Differentiation 8 Positive (CD8+) Cell Count(Baseline (Day 1 pre-dose), Day 8, Day 15 and Day 50)
  • Change From Baseline in Percent CD4+ Cell Count and Percent CD8+ Cell Count(Baseline (Day 1 pre-dose), Day 8, Day 15 and Day 50)
  • Number of Participants With Treatment Emergent Non-serious Adverse Event (Non-SAE) and Serious AE (SAE)(Up to 50 days)
  • Number of Participants With Any Abnormality in Physical Examination(Up to 50 days)
  • Accumulation Index of BMS-626529 Following QHS Dosing(Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours)
  • Inhibitory Quotient (IQ) of BMS-626529 by Css,Avg and by Lowest Concentration of a Drug During Dosing Interval (Cmin) Following Q12H Dosing(Days 1, 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours; Day 9: pre-dose, 4,12 hours; Day 10: pre-dose, 12 hours; Day 11: pre-dose; Days 5,6,7: pre-morning dose)
  • AUC (Tau) of Ritonavir Following QHS Dosing(Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours)
  • Number of Participants With Worst-case Abnormalities in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)(Up to 50 days)
  • Number of Participants With Worst-case Abnormalities in Body Temperature, Respiratory Rate [RR], and Heart Rate [HR](Up to 50 days)
  • Number of Participants With Worst-case Abnormalities in Electrocardiogram (ECG) Parameters(Up to 50 days)
  • Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters(Up to 50 days)
  • Maximum Observed Plasma Concentration (Cmax) of BMS-626529 Following Q12H Dosing(Days 1, 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours)
  • Cmax of BMS-626529 Following QHS Dosing(Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours)
  • Trough Observed Plasma Concentration (Ctrough) of BMS-626529 Following Q12H Dosing(Days 1, 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours; Days 5,6,7: pre-morning dose)
  • Ctrough of BMS-626529 Following QHS Dosing(Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours; Days 5,6,7: pre-evening dose)
  • Area Under the Concentration-time Curve in One Dosing Interval (AUC [Tau]) of BMS-626529 Following Q12H Dosing(Days 1, 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours)
  • AUC (0-24) of BMS-626529 Following QHS Dosing(Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours)
  • AUC (Tau) of BMS-626529 Following QHS Dosing(Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours)
  • Area Under the Concentration-time Curve Over a 24-hour Period (AUC [0-24]) of BMS-626529 Following Q12H Dosing(Day 8: pre-morning dose, 1,2,3,4,5,6,8,12, 13,14,15,16,17,18,20 hours)
  • Inhibitory Quotient of BMS-626529 by Ctrough Following Q12H Dosing(Days 1, 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours; Day 9: pre-dose, 4,12 hours; Day 10: pre-dose, 12 hours; Day 11: pre-dose; Days 5,6,7: pre-morning dose)
  • Inhibitory Quotient of BMS-626529 by Ctrough Following QHS Dosing(Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours; Days 2: pre-evening dose, 12,16 hours; Day 9: pre-dose, 12,16 hours; Day 10: pre-dose, 12 hours; Day 11: pre-dose; Days 5,6,7: pre-evening dose)
  • AUC (Tau) of Ritonavir Following Q12H Dosing(Days 1, 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours)
  • AUC (0-24) of Ritonavir Following QHS Dosing(Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours)
  • Accumulation Index of Ritonavir Following QHS Dosing(Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours)
  • Accumulation Index (AI) of BMS-626529 Following Q12H Dosing(Day 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours)
  • Inhibitory Quotient (IQ) of BMS-626529 by Css,Avg and by Lowest Concentration of a Drug During Dosing Interval (Cmin) Following QHS Dosing(Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours; Day 2: pre-evening dose, 12,16 hours; Day 9: pre-dose, 12,16 hours; Day 10: pre-dose, 12 hours; Day 11: pre-dose; Days 5,6,7: pre-evening dose)
  • Cmax of Ritonavir Following Q12H Dosing(Days 1, 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours)
  • Cmax of Ritonavir Following QHS Dosing(Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours)
  • Ctrough of Ritonavir Following Q12H Dosing(Days 1, 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours; Days 5,6,7: pre-morning dose)
  • Ctrough of Ritonavir Following QHS Dosing(Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours; Days 5,6,7: pre-evening dose)
  • AUC (0-24) of Ritonavir Following Q12H Dosing(Day 8: pre-morning dose, 1,2,3,4,5,6,8,12, 13,14,15,16,17,18,20 hours)
  • Accumulation Index of Ritonavir Following Q12H Dosing(Day 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours)

Investigators

Sponsor Class
Industry
Responsible Party
Sponsor

Study Sites (1)

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