HIV InfectionsPhase 2NCT01009814
Pharmacodynamics, Safety and Pharmacokinetics of BMS-663068, an HIV Attachment Inhibitor, in HIV-1
A Phase 2 study testing BMS-663068 and Ritonavir in people with HIV Infections, run by ViiV Healthcare at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- BMS-663068 and Ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteGermany
- Study dates
- 23 Nov 2009to 25 Jun 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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 locations and contacts
1 site in 1 country.
About this study
Official title: Randomized, Open Label, Multiple-Dose Study to Evaluate the Pharmacodynamics, Safety and Pharmacokinetics of BMS-663068 in HIV-1 Infected Subjects
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
- Being tested
- BMS-663068, Ritonavir
- Keywords
- HIV, HIV attachment inhibitor, attachment inhibitor
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMS-663068Drug
BMS-663068 will be administered as a tablet formulation
RitonavirDrug
Ritonavir will be administered as a capsule.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: BMS-663068; Drug: 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. Receives: Drug: BMS-663068; Drug: 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. Receives: Drug: BMS-663068; Drug: 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. Receives: Drug: BMS-663068; Drug: Ritonavir |
| BMS-663068 1200 mg Q12H | Experimental | All participants received BMS-663068 1200 mg Q12H from Day 1 to Day 8. Receives: Drug: BMS-663068 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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)
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.
Measured: Up to 50 days
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.
Measured: Up to 50 days
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.
Measured: Up to 50 days
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.
Measured: Up to 50 days
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.
Measured: Up to 50 days
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.
Measured: Up to 50 days
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.
Measured: 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
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).
Measured: 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
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).
Measured: 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
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).
Measured: 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
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).
Measured: 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 (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).
Measured: 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
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.
Measured: Day 8: pre-morning dose, 1,2,3,4,5,6,8,12, 13,14,15,16,17,18,20 hours
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.
Measured: Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours
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).
Measured: Day 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours
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).
Measured: 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
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.
Measured: 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 (IQ) of BMS-626529 by Css,Avg and by Lowest Concentration of a Drug During Dosing Interval (Cmin) 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 measures were used in evaluating IQ: Cmin and Css,avg. Geometric mean and geometric coefficient of variation are presented.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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).
Measured: Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours
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).
Measured: 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
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).
Measured: Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours; Days 5,6,7: pre-evening dose
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).
Measured: 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 (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).
Measured: Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours
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.
Measured: Day 8: pre-morning dose, 1,2,3,4,5,6,8,12, 13,14,15,16,17,18,20 hours
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.
Measured: Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours
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).
Measured: Day 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours
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).
Measured: Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2009 (estimated)
- Study start23 Nov 2009
- Primary completion25 Jun 2010
- Study completion25 Jun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by ViiV HealthcareThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- ViiV Healthcare
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, ViiV Healthcare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01009814
- Sponsor's protocol ID
- 206267
- Other IDs
- AI438-006
- Status last verified
- Oct 2019
- First submitted
- 6 Nov 2009
- Last updated
- 3 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 26902761Ray 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.
PubMed 23614999Nettles 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.
PubMed 22896665
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Open Label, Multiple-Dose Study to Evaluate the Pharmacodynamics, Safety and Pharmacokinetics of BMS-663068 in HIV-1 Infected Subjects
- ClinicalTrials.gov ID
- NCT01009814
- Acronym / sponsor ID
- 206267
- Conditions
- HIV Infections
- Keywords
- HIV, HIV attachment inhibitor, attachment inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- ViiV HealthcareIndustry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Study start
- 23 Nov 2009 (actual)
- Primary completion
- 25 Jun 2010 (actual)
- Study completion
- 25 Jun 2010 (actual)
- First posted
- 9 Nov 2009 (estimated)
- Results
- Posted 3 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| BMS-663068 600 mg Q12H + RTV 100 mg Q12H | Experimental | Drug: BMS-663068, Drug: RitonavirAll participants received BMS-663068 600 milligram (mg) and Ritonavir (RTV) 100 mg every 12 hours (Q12H) from Day 1 to Day 8. |
| BMS-663068 1200 mg QHS + RTV 100 mg QHS | Experimental | Drug: BMS-663068, Drug: RitonavirAll participants received BMS-663068 1200 mg and RTV 100 mg every night (quaque hora somni [QHS]) from Day 1 to Day 8. |
| BMS-663068 1200 mg Q12H + RTV 100 mg Q12H | Experimental | Drug: BMS-663068, Drug: RitonavirAll participants received BMS-663068 1200 mg and RTV 100 mg Q12H from Day 1 to Day 8. |
| BMS-663068 1200 mg Q12H + RTV 100 mg QAM | Experimental | Drug: BMS-663068, Drug: RitonavirAll 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. |
| BMS-663068 1200 mg Q12H | Experimental | Drug: BMS-663068All participants received BMS-663068 1200 mg Q12H from Day 1 to Day 8. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Clade B HIV-1 infected subjects meeting following criteria at screening:
- BMI of 18 to 35 kg/m2, inclusive.
- Not currently co-infected with HCV or HBV
- Men and women, ≥ 18 years of age
Key exclusion criteria (33 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BMS-663068BMS-663068 will be administered as a tablet formulation | Drug | BMS-663068 1200 mg Q12H, BMS-663068 1200 mg Q12H + RTV 100 mg Q12H, BMS-663068 1200 mg Q12H + RTV 100 mg QAM, BMS-663068 1200 mg QHS + RTV 100 mg QHS, BMS-663068 600 mg Q12H + RTV 100 mg Q12H |
| RitonavirRitonavir will be administered as a capsule. | Drug | BMS-663068 1200 mg Q12H + RTV 100 mg Q12H, BMS-663068 1200 mg Q12H + RTV 100 mg QAM, BMS-663068 1200 mg QHS + RTV 100 mg QHS, BMS-663068 600 mg Q12H + RTV 100 mg Q12H |
Primary outcome
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.
32 secondary outcomes
Change From Baseline in Cluster of Differentiation 4 Positive (CD4+) Cell Count and Cluster of Differentiation 8 Positive (CD8+) Cell Count
Time frame: 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
Time frame: 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)
Time frame: Up to 50 days
Number of Participants With Any Abnormality in Physical Examination
Time frame: Up to 50 days
Number of Participants With Worst-case Abnormalities in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Time frame: Up to 50 days
Number of Participants With Worst-case Abnormalities in Body Temperature, Respiratory Rate [RR], and Heart Rate [HR]
Time frame: Up to 50 days
Number of Participants With Worst-case Abnormalities in Electrocardiogram (ECG) Parameters
Time frame: Up to 50 days
Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters
Time frame: Up to 50 days
Maximum Observed Plasma Concentration (Cmax) of BMS-626529 Following Q12H Dosing
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
Cmax of BMS-626529 Following QHS Dosing
Time frame: 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
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
Ctrough of BMS-626529 Following QHS Dosing
Time frame: 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
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
AUC (Tau) of BMS-626529 Following QHS Dosing
Time frame: 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
Time frame: Day 8: pre-morning dose, 1,2,3,4,5,6,8,12, 13,14,15,16,17,18,20 hours
AUC (0-24) of BMS-626529 Following QHS Dosing
Time frame: Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours
Accumulation Index (AI) of BMS-626529 Following Q12H Dosing
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
Accumulation Index of BMS-626529 Following QHS Dosing
Time frame: 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
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
Inhibitory Quotient (IQ) of BMS-626529 by Css,Avg and by Lowest Concentration of a Drug During Dosing Interval (Cmin) Following QHS Dosing
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
Inhibitory Quotient of BMS-626529 by Ctrough Following Q12H Dosing
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
Inhibitory Quotient of BMS-626529 by Ctrough Following QHS Dosing
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
Cmax of Ritonavir Following Q12H Dosing
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
Cmax of Ritonavir Following QHS Dosing
Time frame: Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours
Ctrough of Ritonavir Following Q12H Dosing
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
Ctrough of Ritonavir Following QHS Dosing
Time frame: Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours; Days 5,6,7: pre-evening dose
AUC (Tau) of Ritonavir Following Q12H Dosing
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
AUC (Tau) of Ritonavir Following QHS Dosing
Time frame: Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours
AUC (0-24) of Ritonavir Following Q12H Dosing
Time frame: Day 8: pre-morning dose, 1,2,3,4,5,6,8,12, 13,14,15,16,17,18,20 hours
AUC (0-24) of Ritonavir Following QHS Dosing
Time frame: Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours
Accumulation Index of Ritonavir Following Q12H Dosing
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
Accumulation Index of Ritonavir Following QHS Dosing
Time frame: Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26902761Landry 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.
- Derived from this study: PubMed 23614999Ray 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.
- Derived from this study: PubMed 22896665Nettles 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
ViiV Healthcare
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BMS-663068 and Ritonavir in people with HIV Infections, run by ViiV Healthcare at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01009814, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2020.