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

Primary Purpose

HIV Infections

Status

Completed

Phase

Phase 2

Locations

Germany

Study Type

Interventional

Intervention

BMS-663068

Ritonavir

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring HIV, HIV attachment inhibitor, attachment inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

BMS-663068 600 mg Q12H + RTV 100 mg Q12H

BMS-663068 1200 mg QHS + RTV 100 mg QHS

BMS-663068 1200 mg Q12H + RTV 100 mg Q12H

BMS-663068 1200 mg Q12H + RTV 100 mg QAM

BMS-663068 1200 mg Q12H

Arm Description

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

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

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

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.

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change From Baseline in Cluster of Differentiation 4 Positive (CD4+) Cell Count and Cluster of Differentiation 8 Positive (CD8+) Cell Count

Blood samples were collected for evaluation of CD4+ and CD8+ cells at Baseline (Day 1, pre-dose), Day 8, Day 15 (Follow up) and Day 50 (study discharge). 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.

Change From Baseline in Percent CD4+ Cell Count and Percent CD8+ Cell Count

Blood samples were collected for evaluation of percent CD4+ and percent CD8+ cells at Baseline (Day 1, pre-dose), Day 8, Day 15 (Follow up) and Day 50 (study discharge). Baseline was the last non-missing observation before first dose (Day 1 pre-dose) and change from Baseline was calculated by subtracting Baseline visit value from post-Baseline visit value.

Number of Participants With Treatment Emergent Non-serious Adverse Event (Non-SAE) and Serious AE (SAE)

An AE is any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. Any untoward medical occurrence resulting in death, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent serious outcomes were categorized as SAE. Treatment emergent adverse events (occurred after start of treatment) have been presented.Safety Population comprised of all randomized participants who used the trial medication at least once.

Number of Participants With Any Abnormality in Physical Examination

A complete physical examination included, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. A brief physical examination included, at a minimum assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Any abnormality found by investigator during physical examination were recorded. Number of participants with any abnormality in physical examination during study have been reported.

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

Vital signs including DBP and SBP were recorded. Normal ranges were as following: For DBP, lower limit: value <55 millimeter of mercury (mmHg) and change <-20 mmHg; upper limit: value >90 mmHg and change >20 mmHg). For SBP, lower limit: value <90 mmHg and change <-10 mmHg; upper limit: value >140 mmHg and change >10 mmHg. Number of participants with worst-case abnormalities are presented. Worst-case abnormality was defined as: (1) Below Normal: at least one post-Baseline assessment was below normal range, and no post-Baseline assessment was above normal range. (2) Above Normal: at least one post-Baseline assessment was above normal range, and no post-Baseline assessment was below normal range. (3) Within Normal: all post-Baseline assessments were within normal range. It was to be considered as 'Missing' when there were no post-Baseline assessments.

Number of Participants With Worst-case Abnormalities in Body Temperature, Respiratory Rate [RR], and Heart Rate [HR]

Vital signs (body temperature, RR, and HR) were recorded. Normal range were: For HR, lower limit: 55 beats per minute (bpm) and change <-15 bpm; upper limit: >100 bpm and change >30 bpm). For temperature, lower limit: 36.0 Celsius; upper limit: >37.5 Celsius or change >1.7 Celsius). For RR, lower limit: 8 breaths per minute; upper limit: >16 breaths per minute or change >10 breaths per minute. Number of participants with worst-case abnormalities are presented. Worst-case abnormality was defined as: (1) Below Normal: at least one post-Baseline assessment was below normal range, and no post-Baseline assessment was above normal range. (2) Above Normal: at least one post-Baseline assessment was above normal range, and no post-Baseline assessment was below normal range. (3) Within Normal: all post-Baseline assessments were within normal range. It was to be considered as 'Missing' when there were no post-Baseline assessments.

Number of Participants With Worst-case Abnormalities in Electrocardiogram (ECG) Parameters

A 12-lead ECG was recorded during the study using an ECG machine that automatically measures ECG parameters. Normal range for ECG parameters were: PR interval (upper: 200 milliseconds [ms]); QRS (lower: 50 ms; upper: 120 ms); Corrected QT interval by Bazett formula (QTcB) (change from Baseline - increases by > 30 ms); Corrected QT interval by Fredericia formula (QTcF) (change from Baseline - increases by > 30 ms). Number of participants with worst-case abnormalities are presented which was defined as: (1) Below Normal: at least one post-Baseline assessment was below normal range, and no post-Baseline assessment was above normal range. (2) Above Normal: at least one post-Baseline assessment was above normal range, and no post-Baseline assessment was below normal range. Within Normal: all post-Baseline assessments were within normal range. It was to be considered as 'Missing' when there were no post-Baseline assessments.

Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters

Laboratory parameters included hematology, clinical chemistry and urine parameters. Clinically significant abnormal laboratory findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Any abnormal laboratory test results which were considered clinically significant by the investigator were recorded on the case report form. Number of participants with any clinically significant abnormalities in laboratory parameters have been presented.

Maximum Observed Plasma Concentration (Cmax) of BMS-626529 Following Q12H Dosing

Blood samples were collected at indicated time points to assess Cmax of BMS-626529 following Q12H dosing. Geometric mean and geometric coefficient of variation are presented for Day 1, Day 8 morning dose (Anti Meridiem [AM]), Day 8 evening dose (Post Meridiem [PM]) and Day 8 morning + evening dose (AM+PM). Pharmacokinetic parameter values were derived by non-compartmental methods. Pharmacokinetic (PK) Population was used which comprised of all participants who receive BMS-663068 and provided pharmacokinetic samples.

Cmax of BMS-626529 Following QHS Dosing

Blood samples were collected at indicated time points to assess Cmax of BMS-626529 following QHS dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 1, Day 8 evening dose (PM) and Day 8 morning (AM) + evening dose (PM).

Trough Observed Plasma Concentration (Ctrough) of BMS-626529 Following Q12H Dosing

Blood samples were collected at indicated time points to access Ctrough of BMS-626529 following Q12H dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 1, Days 5, 6, 7, 8, Day 8 morning dose (AM) and Day 8 evening dose (PM).

Ctrough of BMS-626529 Following QHS Dosing

Blood samples were collected at indicated time points to assess Ctrough of BMS-626529 following QHS dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 1, Days 5, 6, 7, 8 and Day 8 evening dose (PM).

Area Under the Concentration-time Curve in One Dosing Interval (AUC [Tau]) of BMS-626529 Following Q12H Dosing

Blood samples were collected at indicated time points to assess AUC (tau) of BMS-626529 following Q12H dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 1, Day 8 morning dose (AM) and Day 8 evening dose (PM).

AUC (Tau) of BMS-626529 Following QHS Dosing

Blood samples were collected at indicated time points to assess AUC (tau) of BMS-626529 following QHS dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 1 and Day 8 evening dose (PM).

Area Under the Concentration-time Curve Over a 24-hour Period (AUC [0-24]) of BMS-626529 Following Q12H Dosing

Blood samples were collected at indicated time points to assess AUC (0-24) of BMS-626529 following Q12H dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 8.

AUC (0-24) of BMS-626529 Following QHS Dosing

Blood samples were collected at indicated time points to assess AUC (0-24) of BMS-626529 following QHS dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 8.

Accumulation Index (AI) of BMS-626529 Following Q12H Dosing

Blood samples were collected at indicated time points to assess Accumulation Index of BMS-626529 following Q12H dosing. AI was calculated as ratio of AUC(tau) at steady-state to AUC(tau) after the first dose. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 8 morning dose (AM).

Accumulation Index of BMS-626529 Following QHS Dosing

Blood samples were collected at indicated time points to assess Accumulation Index of BMS-626529 following QHS dosing. AI was calculated as ratio of AUC(tau) at steady-state to AUC(tau) after the first dose. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 8 evening dose (PM).

Inhibitory Quotient (IQ) of BMS-626529 by Css,Avg and by Lowest Concentration of a Drug During Dosing Interval (Cmin) Following Q12H Dosing

Blood samples were collected at indicated time points to assess IQ of BMS-626529. Inhibitory quotient was calculated as the ratio of BMS-626529 in vivo exposure to in vitro measured protein binding adjusted EC90 (PBA-EC90). The following in vivo exposure measures were used in evaluating IQ: Cmin and Css,avg. Geometric mean and geometric coefficient of variation are presented.

Inhibitory Quotient (IQ) of BMS-626529 by Css,Avg and by Lowest Concentration of a Drug During Dosing Interval (Cmin) Following QHS Dosing

Inhibitory Quotient of BMS-626529 by Ctrough Following Q12H Dosing

Blood samples were collected at indicated time points to assess IQ of BMS-626529. Inhibitory quotient was calculated as the ratio of BMS-626529 in vivo exposure to in vitro measured protein binding adjusted EC90 (PBA-EC90). The following in vivo exposure measure was used in evaluating IQ: Ctrough. Geometric mean and geometric coefficient of variation are presented.

Inhibitory Quotient of BMS-626529 by Ctrough Following QHS Dosing

Blood samples were collected at indicated time points to assess IQ of BMS-626529. Inhibitory quotient was calculated as the ratio of BMS-626529 in vivo exposure to in vitro measured protein binding adjusted EC90 (PBA-EC90). The following in vivo exposure measure was used in evaluating IQ: Ctrough. Geometric mean and geometric coefficient of variation are presented.

Cmax of Ritonavir Following Q12H Dosing

Blood samples were collected at indicated time points to assess Cmax of ritonavir following Q12H dosing. Geometric mean and geometric coefficient of variation are presented for Day 1, Day 8 morning dose (AM), Day 8 evening dose (PM) and Day 8 morning + evening dose (AM+PM). Pharmacokinetic parameter values were derived by non-compartmental methods. PK Population was used which comprised of all participants who receive ritonavir and provided pharmacokinetic samples.

Cmax of Ritonavir Following QHS Dosing

Blood samples were collected at indicated time points to assess Cmax of ritonavir following QHS dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 1, Day 8 evening dose (PM) and Day 8 morning (AM) + evening dose (PM).

Ctrough of Ritonavir Following Q12H Dosing

Blood samples were collected at indicated time points to access Ctrough of ritonavir following Q12H dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 1, Days 5, 6, 7, 8, Day 8 morning dose (AM) and Day 8 evening dose (PM).

Ctrough of Ritonavir Following QHS Dosing

Blood samples were collected at indicated time points to assess Ctrough of ritonavir following QHS dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 1, Days 5, 6, 7, 8 and Day 8 evening dose (PM).

AUC (Tau) of Ritonavir Following Q12H Dosing

Blood samples were collected at indicated time points to assess AUC (tau) of ritonavir following Q12H dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 1, Day 8 morning dose (AM) and Day 8 evening dose (PM).

AUC (Tau) of Ritonavir Following QHS Dosing

Blood samples were collected at indicated time points to assess AUC (tau) of ritonavir following QHS dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 1 and Day 8 evening dose (PM).

AUC (0-24) of Ritonavir Following Q12H Dosing

Blood samples were collected at indicated time points to assess AUC (0-24) of ritonavir following Q12H dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 8.

AUC (0-24) of Ritonavir Following QHS Dosing

Blood samples were collected at indicated time points to assess AUC (0-24) of ritonavir following QHS dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 8.

Accumulation Index of Ritonavir Following Q12H Dosing

Blood samples were collected at indicated time points to assess Accumulation Index of ritonavir following Q12H dosing. AI was calculated as ratio of AUC(tau) at steady-state to AUC(tau) after the first dose. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 8 morning dose (AM).

Accumulation Index of Ritonavir Following QHS Dosing

Blood samples were collected at indicated time points to assess Accumulation Index of ritonavir following QHS dosing. AI was calculated as ratio of AUC(tau) at steady-state to AUC(tau) after the first dose. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 8 evening dose (PM).

Full Information

NCT ID

NCT01009814

First Posted

November 6, 2009

Last Updated

December 13, 2019

Sponsor

ViiV Healthcare

Collaborators

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT01009814

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Completed

Study Start Date

November 23, 2009 (Actual)

Primary Completion Date

June 25, 2010 (Actual)

Study Completion Date

June 25, 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ViiV Healthcare

Collaborators

GlaxoSmithKline

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infections

Keywords

HIV, HIV attachment inhibitor, attachment inhibitor

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

50 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BMS-663068 600 mg Q12H + RTV 100 mg Q12H

Arm Type

Experimental

Arm Description

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

Arm Title

BMS-663068 1200 mg QHS + RTV 100 mg QHS

Arm Type

Experimental

Arm Description

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

Arm Title

BMS-663068 1200 mg Q12H + RTV 100 mg Q12H

Arm Type

Experimental

Arm Description

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

Arm Title

BMS-663068 1200 mg Q12H + RTV 100 mg QAM

Arm Type

Experimental

Arm 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.

Arm Title

BMS-663068 1200 mg Q12H

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

BMS-663068

Intervention Description

BMS-663068 will be administered as a tablet formulation

Intervention Type

Drug

Intervention Name(s)

Ritonavir

Intervention Description

Ritonavir will be administered as a capsule.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Baseline and Day 9

Secondary Outcome Measure Information:

Title

Change From Baseline in Cluster of Differentiation 4 Positive (CD4+) Cell Count and Cluster of Differentiation 8 Positive (CD8+) Cell Count

Description

Time Frame

Baseline (Day 1 pre-dose), Day 8, Day 15 and Day 50

Title

Change From Baseline in Percent CD4+ Cell Count and Percent CD8+ Cell Count

Description

Time Frame

Baseline (Day 1 pre-dose), Day 8, Day 15 and Day 50

Title

Number of Participants With Treatment Emergent Non-serious Adverse Event (Non-SAE) and Serious AE (SAE)

Description

Time Frame

Up to 50 days

Title

Number of Participants With Any Abnormality in Physical Examination

Description

Time Frame

Up to 50 days

Title

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

Description

Time Frame

Up to 50 days

Title

Number of Participants With Worst-case Abnormalities in Body Temperature, Respiratory Rate [RR], and Heart Rate [HR]

Description

Time Frame

Up to 50 days

Title

Number of Participants With Worst-case Abnormalities in Electrocardiogram (ECG) Parameters

Description

Time Frame

Up to 50 days

Title

Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters

Description

Time Frame

Up to 50 days

Title

Maximum Observed Plasma Concentration (Cmax) of BMS-626529 Following Q12H Dosing

Description

Time Frame

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

Title

Cmax of BMS-626529 Following QHS Dosing

Description

Time Frame

Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours

Title

Trough Observed Plasma Concentration (Ctrough) of BMS-626529 Following Q12H Dosing

Description

Time Frame

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

Title

Ctrough of BMS-626529 Following QHS Dosing

Description

Time Frame

Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours; Days 5,6,7: pre-evening dose

Title

Area Under the Concentration-time Curve in One Dosing Interval (AUC [Tau]) of BMS-626529 Following Q12H Dosing

Description

Time Frame

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

Title

AUC (Tau) of BMS-626529 Following QHS Dosing

Description

Time Frame

Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours

Title

Area Under the Concentration-time Curve Over a 24-hour Period (AUC [0-24]) of BMS-626529 Following Q12H Dosing

Description

Time Frame

Day 8: pre-morning dose, 1,2,3,4,5,6,8,12, 13,14,15,16,17,18,20 hours

Title

AUC (0-24) of BMS-626529 Following QHS Dosing

Description

Time Frame

Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours

Title

Accumulation Index (AI) of BMS-626529 Following Q12H Dosing

Description

Time Frame

Day 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours

Title

Accumulation Index of BMS-626529 Following QHS Dosing

Description

Time Frame

Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours

Title

Inhibitory Quotient (IQ) of BMS-626529 by Css,Avg and by Lowest Concentration of a Drug During Dosing Interval (Cmin) Following Q12H Dosing

Description

Time Frame

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

Title

Inhibitory Quotient (IQ) of BMS-626529 by Css,Avg and by Lowest Concentration of a Drug During Dosing Interval (Cmin) Following QHS Dosing

Description

Time Frame

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

Title

Inhibitory Quotient of BMS-626529 by Ctrough Following Q12H Dosing

Description

Blood samples were collected at indicated time points to assess IQ of BMS-626529. Inhibitory quotient was calculated as the ratio of BMS-626529 in vivo exposure to in vitro measured protein binding adjusted EC90 (PBA-EC90). The following in vivo exposure measure was used in evaluating IQ: Ctrough. Geometric mean and geometric coefficient of variation are presented.

Time Frame

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

Title

Inhibitory Quotient of BMS-626529 by Ctrough Following QHS Dosing

Description

Blood samples were collected at indicated time points to assess IQ of BMS-626529. Inhibitory quotient was calculated as the ratio of BMS-626529 in vivo exposure to in vitro measured protein binding adjusted EC90 (PBA-EC90). The following in vivo exposure measure was used in evaluating IQ: Ctrough. Geometric mean and geometric coefficient of variation are presented.

Time Frame

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

Title

Cmax of Ritonavir Following Q12H Dosing

Description

Time Frame

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

Title

Cmax of Ritonavir Following QHS Dosing

Description

Time Frame

Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours

Title

Ctrough of Ritonavir Following Q12H Dosing

Description

Time Frame

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

Title

Ctrough of Ritonavir Following QHS Dosing

Description

Time Frame

Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours; Days 5,6,7: pre-evening dose

Title

AUC (Tau) of Ritonavir Following Q12H Dosing

Description

Time Frame

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

Title

AUC (Tau) of Ritonavir Following QHS Dosing

Description

Time Frame

Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours

Title

AUC (0-24) of Ritonavir Following Q12H Dosing

Description

Time Frame

Day 8: pre-morning dose, 1,2,3,4,5,6,8,12, 13,14,15,16,17,18,20 hours

Title

AUC (0-24) of Ritonavir Following QHS Dosing

Description

Time Frame

Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours

Title

Accumulation Index of Ritonavir Following Q12H Dosing

Description

Time Frame

Day 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours

Title

Accumulation Index of Ritonavir Following QHS Dosing

Description

Time Frame

Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

ViiV Healthcare

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Berlin

ZIP/Postal Code

13353

Country

Germany

12. IPD Sharing Statement

Citations:

PubMed Identifier

26902761

Citation

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.

Results Reference

derived

PubMed Identifier

23614999

Citation

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.

Results Reference

derived

PubMed Identifier

22896665

Citation

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.

Results Reference

derived

Learn more about this trial

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

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