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| ID | Type | Description | Link |
|---|---|---|---|
| AI438-006 | Other Identifier | Bristol-Myers Squibb |
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| Name | Class |
|---|---|
| GlaxoSmithKline | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
|
| BMS-663068 1200 mg Q12H | Experimental | All participants received BMS-663068 1200 mg Q12H from Day 1 to Day 8. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BMS-663068 | Drug | BMS-663068 will be administered as a tablet formulation |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
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
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | ViiV Healthcare | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Berlin | 13353 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26902761 | Derived | 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. | |
| 23614999 |
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A total of 75 participants were screened, of which 25 were screen failure, and 50 eligible participants were enrolled into the study and were randomized.
This was a randomized, open label, multiple-dose study to evaluate the pharmacodynamics, safety and pharmacokinetics of BMS-663068 in human immunodeficiency virus 1 (HIV-1) infected participants. The study was conducted at single center in Germany.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| FG004 | BMS-663068 1200 mg Q12H | All participants received BMS-663068 1200 mg Q12H from Day 1 to Day 8. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | BMS-663068 1200 mg QHS + RTV 100 mg QHS |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Pharmacodynamic Population. It comprised of all participants for whom pharmacodynamic measurements were available at Baseline and at least one other time. | Posted | Mean | Standard Error | Log10 copies per milliliter (c/mL) | Baseline and Day 9 |
Serious adverse events (SAEs) and Non-serious adverse events (Non-SAEs) were collected from the start of the study treatment up to 50 days.
SAEs and Non-SAEs were reported by treatment for the Safety Population which comprised of all randomized participants who used the trial medication at least once.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| PALPITATIONS | Cardiac disorders | MedDRA 19.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 8, 2010 | Jul 18, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 7, 2010 | Jul 18, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| ID | Term |
|---|---|
| C576364 | fostemsavir |
| D019438 | Ritonavir |
| ID | Term |
|---|---|
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
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| Ritonavir | Drug | Ritonavir will be administered as a capsule. |
|
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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). | 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). | 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). | 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). | 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). | 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. | 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. | 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). | 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). | 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. | 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. | 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. | 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. | 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. | 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). | 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). | 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). | 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). | 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). | 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. | 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. | 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). | 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). | Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours |
| Derived |
| 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. |
| 22896665 | Derived | 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. |
All participants received BMS-663068 1200 mg and RTV 100 mg every night (quaque hora somni [QHS]) from Day 1 to Day 8.
| BG002 | 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. |
| BG003 | 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. |
| BG004 | BMS-663068 1200 mg Q12H | All participants received BMS-663068 1200 mg Q12H from Day 1 to Day 8. |
| BG005 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| ID | Title | Description |
|---|
| OG000 | 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. |
| OG001 | 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. |
| OG002 | 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. |
| OG003 | 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. |
| OG004 | BMS-663068 1200 mg Q12H | All participants received BMS-663068 1200 mg Q12H from Day 1 to Day 8. |
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| Secondary | 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. | Pharmacodynamic Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). | Posted | Mean | Standard Error | Cells per microliter (cells/μL) | Baseline (Day 1 pre-dose), Day 8, Day 15 and Day 50 |
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| Secondary | 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. | Pharmacodynamic Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). | Posted | Mean | Standard Error | Percent cells per microliter | Baseline (Day 1 pre-dose), Day 8, Day 15 and Day 50 |
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| Secondary | 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. | Safety Population | Posted | Count of Participants | Participants | Up to 50 days |
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| Secondary | 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. | Safety Population | Posted | Count of Participants | Participants | Up to 50 days |
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| Secondary | 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. | Safety Population | Posted | Count of Participants | Participants | Up to 50 days |
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| Secondary | 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. | Safety Population | Posted | Count of Participants | Participants | Up to 50 days |
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| Secondary | 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. | Safety Population | Posted | Count of Participants | Participants | Up to 50 days |
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| Secondary | 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. | Safety Population | Posted | Count of Participants | Participants | Up to 50 days |
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| Secondary | 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. | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | Micrograms per milliliter (μg/mL) | 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 |
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| Secondary | 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). | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | μg/mL | Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours |
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| Secondary | 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). | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | Micrograms per milliliter (μg/mL) | 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 |
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| Secondary | 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). | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | μg/mL | Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours; Days 5,6,7: pre-evening dose |
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| Secondary | 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). | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*micrograms per milliliter | 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 |
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| Secondary | 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). | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*micrograms per milliliter | Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours |
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| Secondary | 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. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*micrograms per milliliter | Day 8: pre-morning dose, 1,2,3,4,5,6,8,12, 13,14,15,16,17,18,20 hours |
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| Secondary | 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. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*micrograms per milliliter | Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours |
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| Secondary | 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). | PK Population. Only those participants with data available at the specified time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio of AUC | Day 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours |
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| Secondary | 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). | PK Population. Only those participants with data available at the specified time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio of AUC | Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours |
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| Secondary | 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. | PK Population. Only those participants with data available at the specified time points were analyzed. No evidence of a correlation between changes in viral load from Baseline (on Day 9 or the nadir) and the BMS-626529 PK parameters was found. Log10 PBA EC90 and IQs of Cmin and Css,avg were found to correlate with antiviral activity. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | 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 |
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| Secondary | 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. | PK Population. Only those participants with data available at the specified time points were analyzed. No evidence of a correlation between changes in viral load from Baseline (on Day 9 or the nadir) and the BMS-626529 PK parameters was found. Log10 PBA EC90 and IQs of Cmin and Css,avg were found to correlate with antiviral activity. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | 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 |
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| Secondary | 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. | PK Population. Only those participants with data available at the specified time points were analyzed. No evidence of a correlation between changes in viral load from Baseline (on Day 9 or the nadir) and the BMS-626529 PK parameters was found. Log10 PBA EC90 and IQs of Cmin and Css,avg were found to correlate with antiviral activity. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | 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 |
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| Secondary | 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. | PK Population. Only those participants with data available at the specified time points were analyzed. No evidence of a correlation between changes in viral load from Baseline (on Day 9 or the nadir) and the BMS-626529 PK parameters was found. Log10 PBA EC90 and IQs of Cmin and Css,avg were found to correlate with antiviral activity. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | 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 |
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| Secondary | 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. | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | Micrograms per milliliter (μg/mL) | 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 |
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| Secondary | 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). | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | μg/mL | Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours |
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| Secondary | 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). | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | Micrograms per milliliter (μg/mL) | 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 |
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| Secondary | 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). | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | μg/mL | Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours; Days 5,6,7: pre-evening dose |
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| Secondary | 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). | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*micrograms per milliliter | 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 |
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| Secondary | 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). | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*micrograms per milliliter | Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours |
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| Secondary | 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. | PK Population. Only those participants with data available at the specified time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*micrograms per milliliter | Day 8: pre-morning dose, 1,2,3,4,5,6,8,12, 13,14,15,16,17,18,20 hours |
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| Secondary | 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. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*micrograms per milliliter | Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours |
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| Secondary | 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). | PK Population. Only those participants with data available at the specified time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio of AUC | Day 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours |
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| Secondary | 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). | PK Population. Only those participants with data available at the specified time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio of AUC | Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours |
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| 0 |
| 10 |
| 0 |
| 10 |
| 8 |
| 10 |
| EG001 | 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. | 0 | 10 | 0 | 10 | 5 | 10 |
| EG002 | 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. | 0 | 10 | 0 | 10 | 9 | 10 |
| EG003 | 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. | 0 | 10 | 0 | 10 | 8 | 10 |
| EG004 | BMS-663068 1200 mg Q12H | All participants received BMS-663068 1200 mg Q12H from Day 1 to Day 8. | 0 | 10 | 0 | 10 | 9 | 10 |
| EYE PRURITUS | Eye disorders | MedDRA 19.1 | Systematic Assessment |
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| ABDOMINAL PAIN | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
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| DIARRHOEA | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
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| NAUSEA | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
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| TOOTHACHE | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
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| ASTHENIA | General disorders | MedDRA 19.1 | Systematic Assessment |
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| CHEST PAIN | General disorders | MedDRA 19.1 | Systematic Assessment |
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| DISCOMFORT | General disorders | MedDRA 19.1 | Systematic Assessment |
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| FATIGUE | General disorders | MedDRA 19.1 | Systematic Assessment |
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| INFLUENZA LIKE ILLNESS | General disorders | MedDRA 19.1 | Systematic Assessment |
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| ABSCESS JAW | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
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| GONORRHOEA | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
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| NASOPHARYNGITIS | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
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| RHINITIS | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
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| ARTHRALGIA | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| FLANK PAIN | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| MYALGIA | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| PAIN IN EXTREMITY | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| DIZZINESS | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
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| HEADACHE | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
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| NEURALGIA | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
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| PRESYNCOPE | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
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| SYNCOPE | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
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| DISORIENTATION | Psychiatric disorders | MedDRA 19.1 | Systematic Assessment |
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| LISTLESS | Psychiatric disorders | MedDRA 19.1 | Systematic Assessment |
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| MICTURITION URGENCY | Renal and urinary disorders | MedDRA 19.1 | Systematic Assessment |
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| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
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| BLISTER | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| DRY SKIN | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| ERYTHEMA | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| HYPERHIDROSIS | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| PRURITUS | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| RASH | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| RASH PRURITIC | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
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GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| CD4+, Day 15, n=9, 9, 10, 10, 10 |
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| CD4+, Day 50, n=9, 9, 10, 10, 9 |
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| CD8+, Day 8, n=9, 9, 10, 10, 10 |
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| CD8+, Day 15, n=9, 9, 10, 10, 10 |
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| CD8+, Day 50, n=9, 9, 10, 10, 9 |
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| Percent CD4+, Day 15, n=9, 9, 10, 10, 10 |
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| Percent CD4+, Day 50, n=9, 9, 10, 10, 9 |
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| Percent CD8+, Day 8, n=9, 9, 10, 10, 10 |
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| Percent CD8+, Day 15, n=9, 9, 10, 10, 10 |
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| Percent CD8+, Day 50, n=9, 9, 10, 10, 9 |
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| SAE |
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| SBP, Below Normal |
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| SBP, Within Normal |
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| DBP, Above Normal |
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| DBP, Below Normal |
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| DBP, Within Normal |
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| HR, Below Normal |
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| HR, Within Normal |
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| RR, Above Normal |
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| RR, Below Normal |
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| RR, Within Normal |
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| Temperature, Above Normal |
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| Temperature, Below Normal |
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| Temperature, Within Normal |
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| PR interval, Below Normal |
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| PR interval, Within Normal |
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| QTcB, Above Normal |
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| QTcB, Below Normal |
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| QTcB, Within Normal |
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| QTcF, Above Normal |
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| QTcF, Below Normal |
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| QTcF, Within Normal |
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| Day 8, AM, n=9,10,10,10 |
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| Day 8, PM, n=9,10,10,10 |
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| Day 8, AM+PM, n=9,10,10,10 |
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| Day 8, AM+PM, n=9 |
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| Day 5, n=9,10,10,10 |
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| Day 6, n=9,10,10,10 |
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| Day 7, n=9,10,10,10 |
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| Day 8, n=9,10,10,10 |
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| Day 8, AM, n=9,10,10,10 |
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| Day 8, PM, n=9,10,10,10 |
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| Day 6, n=9 |
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| Day 7, n=9 |
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| Day 8, n=9 |
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| Day 8, PM, n=9 |
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| Day 8, AM, n=9,10,10,10 |
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| Day 8, PM, n=9,10,10,10 |
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| IQ Css,avg |
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| Day 8, AM, n=9,10,10 |
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| Day 8, PM, n=9,10,0 |
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| Day 8, AM+PM, n=9,10,10 |
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| Day 8, AM+PM, n=9 |
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| Day 5, n=9,10,10 |
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| Day 6, n=9,10,10 |
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| Day 7, n=9,10,10 |
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| Day 8, n=9,10,10 |
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| Day 8, AM, n=9,10,10 |
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| Day 8, PM, n=9,10,0 |
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| Day 6, n=9 |
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| Day 7, n=9 |
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| Day 8, n=9 |
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| Day 8, PM, n=9 |
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| Day 8, AM, n=9,10,10 |
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| Day 8, PM, n=9,10,0 |
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