NCT01009814

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P25-P50 for phase_2 hiv-infections

Timeline
Completed

Started Nov 2009

Shorter than P25 for phase_2 hiv-infections

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 6, 2009

Completed
3 days until next milestone

First Posted

Study publicly available on registry

November 9, 2009

Completed
14 days until next milestone

Study Start

First participant enrolled

November 23, 2009

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 25, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 25, 2010

Completed
9.5 years until next milestone

Results Posted

Study results publicly available

January 3, 2020

Completed
Last Updated

January 3, 2020

Status Verified

October 1, 2019

Enrollment Period

7 months

First QC Date

November 6, 2009

Results QC Date

December 13, 2019

Last Update Submit

December 13, 2019

Conditions

HIV Infections

Keywords

HIV, HIV attachment inhibitor, attachment inhibitor

Outcome Measures

Primary Outcomes (1)

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

    Baseline and Day 9

Secondary Outcomes (32)

  • 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

  • Number of Participants With Worst-case Abnormalities in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

    Up to 50 days

  • +27 more secondary outcomes

Study Arms (5)

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.

Drug: BMS-663068Drug: Ritonavir

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.

Drug: BMS-663068Drug: Ritonavir

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.

Drug: BMS-663068Drug: Ritonavir

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.

Drug: BMS-663068Drug: Ritonavir

BMS-663068 1200 mg Q12H

EXPERIMENTAL

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

Drug: BMS-663068

Interventions

BMS-663068DRUG

BMS-663068 will be administered as a tablet formulation

BMS-663068 1200 mg Q12HBMS-663068 1200 mg Q12H + RTV 100 mg Q12HBMS-663068 1200 mg Q12H + RTV 100 mg QAMBMS-663068 1200 mg QHS + RTV 100 mg QHSBMS-663068 600 mg Q12H + RTV 100 mg Q12H
RitonavirDRUG

Ritonavir will be administered as a capsule.

BMS-663068 1200 mg Q12H + RTV 100 mg Q12HBMS-663068 1200 mg Q12H + RTV 100 mg QAMBMS-663068 1200 mg QHS + RTV 100 mg QHSBMS-663068 600 mg Q12H + RTV 100 mg Q12H

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.
  • +18 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

GSK Investigational Site

Berlin, 13353, Germany

Location

Related Publications (3)

  • Landry I, Zhu L, Abu Tarif M, Hruska M, Sadler BM, Pitsiu M, Joshi S, Hanna GJ, Lataillade M, Boulton DW, Bertz RJ. Model-Based Phase 3 Dose Selection for HIV-1 Attachment Inhibitor Prodrug BMS-663068 in HIV-1-Infected Patients: Population Pharmacokinetics/Pharmacodynamics of the Active Moiety, BMS-626529. Antimicrob Agents Chemother. 2016 Apr 22;60(5):2782-9. doi: 10.1128/AAC.02503-15. Print 2016 May.

    PMID: 26902761DERIVED

  • Ray N, Hwang C, Healy MD, Whitcomb J, Lataillade M, Wind-Rotolo M, Krystal M, Hanna GJ. Prediction of virological response and assessment of resistance emergence to the HIV-1 attachment inhibitor BMS-626529 during 8-day monotherapy with its prodrug BMS-663068. J Acquir Immune Defic Syndr. 2013 Sep 1;64(1):7-15. doi: 10.1097/QAI.0b013e31829726f3.

    PMID: 23614999DERIVED

  • Nettles RE, Schurmann D, Zhu L, Stonier M, Huang SP, Chang I, Chien C, Krystal M, Wind-Rotolo M, Ray N, Hanna GJ, Bertz R, Grasela D. Pharmacodynamics, safety, and pharmacokinetics of BMS-663068, an oral HIV-1 attachment inhibitor in HIV-1-infected subjects. J Infect Dis. 2012 Oct 1;206(7):1002-11. doi: 10.1093/infdis/jis432. Epub 2012 Aug 14.

    PMID: 22896665DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

fostemsavirRitonavir

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Intervention Hierarchy (Ancestors)

ThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Results Point of Contact

Title
GSK Response Center
Organization
GlaxoSmithKline
GSKClinicalSupportHD@gsk.com
866-435-7343

Study Officials

  • GSK Clinical Trials

    ViiV Healthcare

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 6, 2009

First Posted

November 9, 2009

Study Start

November 23, 2009

Primary Completion

June 25, 2010

Study Completion

June 25, 2010

Last Updated

January 3, 2020

Results First Posted

January 3, 2020

Record last verified: 2019-10

Locations

DE(1)