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

NCT ID: NCT01009814

Last Updated: 2020-01-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-23
• Study Completion Date: 2010-06-25

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.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BMS-663068 600 mg Q12H + RTV 100 mg Q12H

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

Group Type: EXPERIMENTAL

BMS-663068

Intervention Type: DRUG

BMS-663068 will be administered as a tablet formulation

Ritonavir

Intervention Type: DRUG

Ritonavir will be administered as a capsule.

BMS-663068 1200 mg QHS + RTV 100 mg QHS

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

Group Type: EXPERIMENTAL

BMS-663068

Intervention Type: DRUG

BMS-663068 will be administered as a tablet formulation

Ritonavir

Intervention Type: DRUG

Ritonavir will be administered as a capsule.

BMS-663068 1200 mg Q12H + RTV 100 mg Q12H

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

Group Type: EXPERIMENTAL

BMS-663068

Intervention Type: DRUG

BMS-663068 will be administered as a tablet formulation

Ritonavir

Intervention Type: DRUG

Ritonavir will be administered as a capsule.

BMS-663068 1200 mg Q12H + RTV 100 mg QAM

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.

Group Type: EXPERIMENTAL

BMS-663068

Intervention Type: DRUG

BMS-663068 will be administered as a tablet formulation

Ritonavir

Intervention Type: DRUG

Ritonavir will be administered as a capsule.

BMS-663068 1200 mg Q12H

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

Group Type: EXPERIMENTAL

BMS-663068

Intervention Type: DRUG

BMS-663068 will be administered as a tablet formulation

Interventions

BMS-663068

BMS-663068 will be administered as a tablet formulation

Intervention Type: DRUG

Ritonavir

Ritonavir will be administered as a capsule.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

ViiV Healthcare

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

GSK Investigational Site

Berlin, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 26902761 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23614999 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22896665 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

AI438-006

Identifier Type: OTHER

Identifier Source: secondary_id

206267

Identifier Type: -

Identifier Source: org_study_id