Human Immunodeficiency Virus Type 1
Conditions
Keywords
Human immunodeficiency virus type 1, HIV-1, HIV-1 treatment-naive, TMC310911, Protease inhibitor, Ritonavir, Antiviral Activity, HIV Infections, Treatment Naive
Brief summary
The purpose of this study is to evaluate the antiviral activity as measured by the change in viral load from baseline in the 14 days following initiation of treatment with 4 different dose regimens of TMC310911 co-administered with ritonavir.
Detailed description
This is an open-label (all people know the identity of the intervention) and randomized (study medication assigned by chance) study in treatment-naive human immunodeficiency virus type 1 (HIV-1)-infected participants (participants who had not been treated with a therapeutic HIV vaccine within 1 year prior to enrollment and who had never been treated with an antiretroviral \[ARV\] medication indicated for the treatment of HIV-infection or ARVs for treatment of hepatitis B infection with anti-HIV activity prior to screening). In this study approximately 32 participants will be enrolled and randomly assigned to receive 4 different dose regimens co-administered with ritonavir (8 participants in each dosing regimen). The trial will consist of a screening period (maximum 6 weeks), a treatment period with TMC310911 (2 weeks), and a follow-up period (4 weeks). Safety evaluation will include assessment of adverse events, clinical laboratory tests, vital sign measurements, physical examinations and electrocardiograms.
Interventions
DRUGTMC310911 75 mg twice daily
TMC310911 75 mg twice daily orally (by mouth) on Days 1 to 14.
DRUGTMC310911 150 mg twice daily
TMC310911 150 mg twice daily orally (by mouth) on Days 1 to 14
DRUGTMC310911 300 mg twice daily
TMC310911 300 mg twice daily orally (by mouth) on Days 1 to 14
DRUGTMC310911 300 mg once daily
TMC310911 300 mg once daily orally (by mouth) on Days 1 to 14
DRUGRitonavir 100 mg twice daily
Ritonavir 100 mg twice daily orally (by mouth) on Days 1 to 14
DRUGRitonavir 100 mg once daily
Ritonavir 100 mg once daily orally (by mouth) on Days 1 to 14
Sponsors
Tibotec Pharmaceuticals, Ireland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Documented human immunodeficiency virus type 1 (HIV-1) infection for at least 6 months prior to the screening date * Participant who has not been treated with a therapeutic HIV vaccine within 1 year prior to enrolment and has never been treated with an antiretroviral (ARV) medication indicated for the treatment of HIV infection or ARVs for treatment of hepatitis B-infection with anti-HIV activity * Participant agrees not to start antiretroviral therapy (ART) before the baseline visit * Able to comply with the protocol requirements and have good accessible veins * HIV-1 plasma viral load at screening visit of above 5,000 HIV-1 Ribonucleic acid copies/mL * CD4+ cell count above 200 cells/mm3 at screening
Exclusion criteria
* HIV-2 infected participants and/or participants with any active or chronic hepato-renal disease * Life expectancy of less than 6 months * Documented acute (primary) HIV-1 infection * Pre-existing protease inhibitor (PI) medication resistance * Any currently active Acquired Immunodeficiency Syndrome (AIDS) - defining illness * Any active clinically significant disease or findings during screening or medical history or physical examination that in the investigator's opinion, would compromise the outcome of the study * Any confirmed grade 3 or 4 toxicity according to the Division of AIDS (DAIDS) grading scale at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) | Baseline (Day 1), Day 8, Day 15 | The antiviral activity of TMC310911 is measured by the change in viral load from baseline in the 14 days of treatment following initiation of treatment with 4 different dosing regimens of TMC310911 coadministered with ritonavir. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period | 14 days | Virologic response is a viral load test result below a chosen threshold value (less than 50 copies/mL, less than 400 copies/mL, or at least 1 log drop in viral load) at any timepoint during a 14-day treatment of 4 different dose regimens of TMC310911 coadministered with 100 mg ritonavir. |
| Mean Changes From Baseline in CD4+ Cell Count | Baseline (Day 1), Day 8, Day 15 | — |
| Maximum Plasma Concentration (Cmax) of TMC310911 | Day 1 and Day 14 | — |
| Fluctuation Index of TMC310911 | Day 14 | Fluctuation index, ie, percentage fluctuation: variation between maximum (Cmax) and minimum (Cmin) plasma concentration at steady-state, calculated as: 100 x (\[Cmax-Cmin\]/Css,av). Css,av is an average steady-state plasma concentration. |
| Area Under the Plasma Concentration-time Curve (AUC12) From the Time of Administration of TMC310911 up to 12 Hours After Dosing | Day 1 and Day 14 | — |
| Predose Plasma Concentration (C0h) of TMC310911 | Day 2, Day 3, Day 4, Day 6, Day 8, Day 10, Day 12 and Day 14 | — |
| Average Steady-state Plasma Concentration (Css,av) of TMC310911 | Day 14 | — |
| Time to Reach the Maximum Plasma Concentration (Tmax) of TMC310911 | Day 1 and Day 14 | — |
Countries
Germany
Participant flow
Recruitment details
This study was conducted in Germany.
Pre-assignment details
In total, 41 participants were screened of whom 33 participants were randomized and treated with TMC310911. All treated participants completed the study; there were no dropouts or discontinuations during the study.
Participants by arm
| Arm | Count |
|---|---|
| TMC310911/Rtv 75/100 mg Twice Daily TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14 | 9 |
| TMC310911/Rtv 150/100 mg Twice Daily TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14 | 8 |
| TMC310911/Rtv 300/100 mg Twice Daily TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14 | 8 |
| TMC310911/Rtv 300/100 mg Once a Day TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14 | 8 |
| Total | 33 |
Baseline characteristics
| Characteristic | TMC310911/Rtv 75/100 mg Twice Daily | TMC310911/Rtv 150/100 mg Twice Daily | TMC310911/Rtv 300/100 mg Twice Daily | TMC310911/Rtv 300/100 mg Once a Day | Total |
|---|---|---|---|---|---|
| Age Continuous | 29.7 years STANDARD_DEVIATION 7.23 | 38.1 years STANDARD_DEVIATION 8.66 | 35.5 years STANDARD_DEVIATION 6.87 | 37.8 years STANDARD_DEVIATION 10.19 | 35.1 years STANDARD_DEVIATION 8.65 |
| Race/Ethnicity, Customized Black | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 32 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 9 | 5 / 8 | 6 / 8 | 3 / 8 |
| serious Total, serious adverse events | 0 / 9 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA)
The antiviral activity of TMC310911 is measured by the change in viral load from baseline in the 14 days of treatment following initiation of treatment with 4 different dosing regimens of TMC310911 coadministered with ritonavir.
Time frame: Baseline (Day 1), Day 8, Day 15
Population: Intent-to treat (ITT) population- participants who received at least 1 dose of study medication (TMC310911).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMC310911/Rtv 75/100 mg Twice Daily | Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) | Baseline | 4.72 log10 copies/mL | Standard Error 0.245 |
| TMC310911/Rtv 75/100 mg Twice Daily | Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) | Day 15 | -1.53 log10 copies/mL | Standard Error 0.117 |
| TMC310911/Rtv 75/100 mg Twice Daily | Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) | Day 8 | -1.30 log10 copies/mL | Standard Error 0.126 |
| TMC310911/Rtv 150/100 mg Twice Daily | Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) | Baseline | 4.36 log10 copies/mL | Standard Error 0.259 |
| TMC310911/Rtv 150/100 mg Twice Daily | Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) | Day 15 | -1.79 log10 copies/mL | Standard Error 0.192 |
| TMC310911/Rtv 150/100 mg Twice Daily | Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) | Day 8 | -1.14 log10 copies/mL | Standard Error 0.147 |
| TMC310911/Rtv 300/100 mg Twice Daily | Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) | Day 8 | -1.07 log10 copies/mL | Standard Error 0.104 |
| TMC310911/Rtv 300/100 mg Twice Daily | Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) | Baseline | 4.78 log10 copies/mL | Standard Error 0.161 |
| TMC310911/Rtv 300/100 mg Twice Daily | Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) | Day 15 | -1.69 log10 copies/mL | Standard Error 0.103 |
| TMC310911/Rtv 300/100 mg Once a Day | Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) | Baseline | 4.71 log10 copies/mL | Standard Error 0.116 |
| TMC310911/Rtv 300/100 mg Once a Day | Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) | Day 15 | -1.55 log10 copies/mL | Standard Error 0.16 |
| TMC310911/Rtv 300/100 mg Once a Day | Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) | Day 8 | -1.06 log10 copies/mL | Standard Error 0.144 |
Secondary
Area Under the Plasma Concentration-time Curve (AUC12) From the Time of Administration of TMC310911 up to 12 Hours After Dosing
Time frame: Day 1 and Day 14
Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC310911)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMC310911/Rtv 75/100 mg Twice Daily | Area Under the Plasma Concentration-time Curve (AUC12) From the Time of Administration of TMC310911 up to 12 Hours After Dosing | Day 1 | 2519 ng.h/mL | Standard Deviation 2123 |
| TMC310911/Rtv 75/100 mg Twice Daily | Area Under the Plasma Concentration-time Curve (AUC12) From the Time of Administration of TMC310911 up to 12 Hours After Dosing | Day 14 | 4031 ng.h/mL | Standard Deviation 3845 |
| TMC310911/Rtv 150/100 mg Twice Daily | Area Under the Plasma Concentration-time Curve (AUC12) From the Time of Administration of TMC310911 up to 12 Hours After Dosing | Day 14 | 10680 ng.h/mL | Standard Deviation 3147 |
| TMC310911/Rtv 150/100 mg Twice Daily | Area Under the Plasma Concentration-time Curve (AUC12) From the Time of Administration of TMC310911 up to 12 Hours After Dosing | Day 1 | 2735 ng.h/mL | Standard Deviation 1572 |
| TMC310911/Rtv 300/100 mg Twice Daily | Area Under the Plasma Concentration-time Curve (AUC12) From the Time of Administration of TMC310911 up to 12 Hours After Dosing | Day 1 | 2990 ng.h/mL | Standard Deviation 2245 |
| TMC310911/Rtv 300/100 mg Twice Daily | Area Under the Plasma Concentration-time Curve (AUC12) From the Time of Administration of TMC310911 up to 12 Hours After Dosing | Day 14 | 16010 ng.h/mL | Standard Deviation 8229 |
| TMC310911/Rtv 300/100 mg Once a Day | Area Under the Plasma Concentration-time Curve (AUC12) From the Time of Administration of TMC310911 up to 12 Hours After Dosing | Day 1 | 10040 ng.h/mL | Standard Deviation 6122 |
| TMC310911/Rtv 300/100 mg Once a Day | Area Under the Plasma Concentration-time Curve (AUC12) From the Time of Administration of TMC310911 up to 12 Hours After Dosing | Day 14 | 17520 ng.h/mL | Standard Deviation 11610 |
Secondary
Average Steady-state Plasma Concentration (Css,av) of TMC310911
Time frame: Day 14
Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC310911).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TMC310911/Rtv 75/100 mg Twice Daily | Average Steady-state Plasma Concentration (Css,av) of TMC310911 | 336.2 ng/mL | Standard Deviation 321.3 |
| TMC310911/Rtv 150/100 mg Twice Daily | Average Steady-state Plasma Concentration (Css,av) of TMC310911 | 889.6 ng/mL | Standard Deviation 262.6 |
| TMC310911/Rtv 300/100 mg Twice Daily | Average Steady-state Plasma Concentration (Css,av) of TMC310911 | 1340 ng/mL | Standard Deviation 689.6 |
| TMC310911/Rtv 300/100 mg Once a Day | Average Steady-state Plasma Concentration (Css,av) of TMC310911 | 887.3 ng/mL | Standard Deviation 567.5 |
Secondary
Fluctuation Index of TMC310911
Fluctuation index, ie, percentage fluctuation: variation between maximum (Cmax) and minimum (Cmin) plasma concentration at steady-state, calculated as: 100 x (\[Cmax-Cmin\]/Css,av). Css,av is an average steady-state plasma concentration.
Time frame: Day 14
Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC310911)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TMC310911/Rtv 75/100 mg Twice Daily | Fluctuation Index of TMC310911 | 181.0 Percent ng/mL | Standard Deviation 80 |
| TMC310911/Rtv 150/100 mg Twice Daily | Fluctuation Index of TMC310911 | 161.3 Percent ng/mL | Standard Deviation 29.22 |
| TMC310911/Rtv 300/100 mg Twice Daily | Fluctuation Index of TMC310911 | 129.2 Percent ng/mL | Standard Deviation 52.89 |
| TMC310911/Rtv 300/100 mg Once a Day | Fluctuation Index of TMC310911 | 331.8 Percent ng/mL | Standard Deviation 55.47 |
Secondary
Maximum Plasma Concentration (Cmax) of TMC310911
Time frame: Day 1 and Day 14
Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC310911)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMC310911/Rtv 75/100 mg Twice Daily | Maximum Plasma Concentration (Cmax) of TMC310911 | Day 1 | 487.9 ng/mL | Standard Deviation 450.3 |
| TMC310911/Rtv 75/100 mg Twice Daily | Maximum Plasma Concentration (Cmax) of TMC310911 | Day 14 | 589.7 ng/mL | Standard Deviation 554.1 |
| TMC310911/Rtv 150/100 mg Twice Daily | Maximum Plasma Concentration (Cmax) of TMC310911 | Day 14 | 1674 ng/mL | Standard Deviation 652.3 |
| TMC310911/Rtv 150/100 mg Twice Daily | Maximum Plasma Concentration (Cmax) of TMC310911 | Day 1 | 623.0 ng/mL | Standard Deviation 358.1 |
| TMC310911/Rtv 300/100 mg Twice Daily | Maximum Plasma Concentration (Cmax) of TMC310911 | Day 1 | 706.3 ng/mL | Standard Deviation 553.2 |
| TMC310911/Rtv 300/100 mg Twice Daily | Maximum Plasma Concentration (Cmax) of TMC310911 | Day 14 | 2256 ng/mL | Standard Deviation 961.9 |
| TMC310911/Rtv 300/100 mg Once a Day | Maximum Plasma Concentration (Cmax) of TMC310911 | Day 1 | 1924 ng/mL | Standard Deviation 1048 |
| TMC310911/Rtv 300/100 mg Once a Day | Maximum Plasma Concentration (Cmax) of TMC310911 | Day 14 | 2963 ng/mL | Standard Deviation 1920 |
Secondary
Mean Changes From Baseline in CD4+ Cell Count
Time frame: Baseline (Day 1), Day 8, Day 15
Population: Intent-to-treat (ITT) Population - all randomized participants who received at least 1 dose of study medication (TMC310911)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMC310911/Rtv 75/100 mg Twice Daily | Mean Changes From Baseline in CD4+ Cell Count | Baseline | 575.7 x 1000000 cells/L | Standard Error 56.97 |
| TMC310911/Rtv 75/100 mg Twice Daily | Mean Changes From Baseline in CD4+ Cell Count | Day 15 | -33.7 x 1000000 cells/L | Standard Error 27.04 |
| TMC310911/Rtv 75/100 mg Twice Daily | Mean Changes From Baseline in CD4+ Cell Count | Day 8 | -21.0 x 1000000 cells/L | Standard Error 41.23 |
| TMC310911/Rtv 150/100 mg Twice Daily | Mean Changes From Baseline in CD4+ Cell Count | Baseline | 464.9 x 1000000 cells/L | Standard Error 61.32 |
| TMC310911/Rtv 150/100 mg Twice Daily | Mean Changes From Baseline in CD4+ Cell Count | Day 8 | 40.3 x 1000000 cells/L | Standard Error 45.19 |
| TMC310911/Rtv 150/100 mg Twice Daily | Mean Changes From Baseline in CD4+ Cell Count | Day 15 | -2.8 x 1000000 cells/L | Standard Error 31.44 |
| TMC310911/Rtv 300/100 mg Twice Daily | Mean Changes From Baseline in CD4+ Cell Count | Day 15 | -2.0 x 1000000 cells/L | Standard Error 41.23 |
| TMC310911/Rtv 300/100 mg Twice Daily | Mean Changes From Baseline in CD4+ Cell Count | Day 8 | -14.8 x 1000000 cells/L | Standard Error 47.59 |
| TMC310911/Rtv 300/100 mg Twice Daily | Mean Changes From Baseline in CD4+ Cell Count | Baseline | 494.0 x 1000000 cells/L | Standard Error 70.43 |
| TMC310911/Rtv 300/100 mg Once a Day | Mean Changes From Baseline in CD4+ Cell Count | Day 15 | 92.5 x 1000000 cells/L | Standard Error 58.7 |
| TMC310911/Rtv 300/100 mg Once a Day | Mean Changes From Baseline in CD4+ Cell Count | Day 8 | 17.9 x 1000000 cells/L | Standard Error 48.2 |
| TMC310911/Rtv 300/100 mg Once a Day | Mean Changes From Baseline in CD4+ Cell Count | Baseline | 479.6 x 1000000 cells/L | Standard Error 39.16 |
Secondary
Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period
Virologic response is a viral load test result below a chosen threshold value (less than 50 copies/mL, less than 400 copies/mL, or at least 1 log drop in viral load) at any timepoint during a 14-day treatment of 4 different dose regimens of TMC310911 coadministered with 100 mg ritonavir.
Time frame: 14 days
Population: Intent-to-treat (ITT) Population- all randomized participants who received at least 1 dose of study medication (TMC310911)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TMC310911/Rtv 75/100 mg Twice Daily | Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period | Viral load less than 50 copies/mL | 0 Participants |
| TMC310911/Rtv 75/100 mg Twice Daily | Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period | At least 1 log10 Viral Load Drop | 9 Participants |
| TMC310911/Rtv 75/100 mg Twice Daily | Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period | Viral load less than 400 copies/mL | 3 Participants |
| TMC310911/Rtv 150/100 mg Twice Daily | Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period | Viral load less than 50 copies/mL | 1 Participants |
| TMC310911/Rtv 150/100 mg Twice Daily | Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period | At least 1 log10 Viral Load Drop | 8 Participants |
| TMC310911/Rtv 150/100 mg Twice Daily | Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period | Viral load less than 400 copies/mL | 4 Participants |
| TMC310911/Rtv 300/100 mg Twice Daily | Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period | Viral load less than 400 copies/mL | 1 Participants |
| TMC310911/Rtv 300/100 mg Twice Daily | Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period | Viral load less than 50 copies/mL | 0 Participants |
| TMC310911/Rtv 300/100 mg Twice Daily | Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period | At least 1 log10 Viral Load Drop | 8 Participants |
| TMC310911/Rtv 300/100 mg Once a Day | Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period | Viral load less than 50 copies/mL | 0 Participants |
| TMC310911/Rtv 300/100 mg Once a Day | Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period | At least 1 log10 Viral Load Drop | 7 Participants |
| TMC310911/Rtv 300/100 mg Once a Day | Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period | Viral load less than 400 copies/mL | 0 Participants |
Secondary
Predose Plasma Concentration (C0h) of TMC310911
Time frame: Day 2, Day 3, Day 4, Day 6, Day 8, Day 10, Day 12 and Day 14
Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC310911).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMC310911/Rtv 75/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 2 | 79.95 ng/mL | Standard Deviation 104.1 |
| TMC310911/Rtv 75/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 3 | 93.98 ng/mL | Standard Deviation 92.9 |
| TMC310911/Rtv 75/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 4 | 88.94 ng/mL | Standard Deviation 113.6 |
| TMC310911/Rtv 75/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 6 | 119.1 ng/mL | Standard Deviation 182.1 |
| TMC310911/Rtv 75/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 8 | 134.5 ng/mL | Standard Deviation 179 |
| TMC310911/Rtv 75/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 10 | 78.51 ng/mL | Standard Deviation 57.88 |
| TMC310911/Rtv 75/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 12 | 104.6 ng/mL | Standard Deviation 82.91 |
| TMC310911/Rtv 75/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 14 | 152.5 ng/mL | Standard Deviation 248.2 |
| TMC310911/Rtv 150/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 10 | 394.4 ng/mL | Standard Deviation 134.4 |
| TMC310911/Rtv 150/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 8 | 665.9 ng/mL | Standard Deviation 461.1 |
| TMC310911/Rtv 150/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 3 | 448.0 ng/mL | Standard Deviation 266.1 |
| TMC310911/Rtv 150/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 14 | 420.9 ng/mL | Standard Deviation 244.6 |
| TMC310911/Rtv 150/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 12 | 518.6 ng/mL | Standard Deviation 288.7 |
| TMC310911/Rtv 150/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 6 | 443.0 ng/mL | Standard Deviation 284.7 |
| TMC310911/Rtv 150/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 4 | 291.3 ng/mL | Standard Deviation 170.2 |
| TMC310911/Rtv 150/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 2 | 207.7 ng/mL | Standard Deviation 122.9 |
| TMC310911/Rtv 300/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 12 | 1110 ng/mL | Standard Deviation 547.5 |
| TMC310911/Rtv 300/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 4 | 1035 ng/mL | Standard Deviation 552.2 |
| TMC310911/Rtv 300/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 6 | 960.5 ng/mL | Standard Deviation 506.9 |
| TMC310911/Rtv 300/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 8 | 1028 ng/mL | Standard Deviation 724.1 |
| TMC310911/Rtv 300/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 10 | 736.1 ng/mL | Standard Deviation 435 |
| TMC310911/Rtv 300/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 14 | 924.8 ng/mL | Standard Deviation 527.9 |
| TMC310911/Rtv 300/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 2 | 231.9 ng/mL | Standard Deviation 199.9 |
| TMC310911/Rtv 300/100 mg Twice Daily | Predose Plasma Concentration (C0h) of TMC310911 | Day 3 | 586.3 ng/mL | Standard Deviation 454.2 |
| TMC310911/Rtv 300/100 mg Once a Day | Predose Plasma Concentration (C0h) of TMC310911 | Day 4 | 191.0 ng/mL | Standard Deviation 175.7 |
| TMC310911/Rtv 300/100 mg Once a Day | Predose Plasma Concentration (C0h) of TMC310911 | Day 6 | 250.0 ng/mL | Standard Deviation 236.1 |
| TMC310911/Rtv 300/100 mg Once a Day | Predose Plasma Concentration (C0h) of TMC310911 | Day 3 | 125.9 ng/mL | Standard Deviation 69.01 |
| TMC310911/Rtv 300/100 mg Once a Day | Predose Plasma Concentration (C0h) of TMC310911 | Day 2 | 45.48 ng/mL | Standard Deviation 28.94 |
| TMC310911/Rtv 300/100 mg Once a Day | Predose Plasma Concentration (C0h) of TMC310911 | Day 8 | 239.6 ng/mL | Standard Deviation 242.6 |
| TMC310911/Rtv 300/100 mg Once a Day | Predose Plasma Concentration (C0h) of TMC310911 | Day 14 | 209.9 ng/mL | Standard Deviation 187.2 |
| TMC310911/Rtv 300/100 mg Once a Day | Predose Plasma Concentration (C0h) of TMC310911 | Day 12 | 250.2 ng/mL | Standard Deviation 181.9 |
| TMC310911/Rtv 300/100 mg Once a Day | Predose Plasma Concentration (C0h) of TMC310911 | Day 10 | 251.7 ng/mL | Standard Deviation 211 |
Secondary
Time to Reach the Maximum Plasma Concentration (Tmax) of TMC310911
Time frame: Day 1 and Day 14
Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC310911)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TMC310911/Rtv 75/100 mg Twice Daily | Time to Reach the Maximum Plasma Concentration (Tmax) of TMC310911 | Day 1 | 5.02 hours |
| TMC310911/Rtv 75/100 mg Twice Daily | Time to Reach the Maximum Plasma Concentration (Tmax) of TMC310911 | Day 14 | 4.98 hours |
| TMC310911/Rtv 150/100 mg Twice Daily | Time to Reach the Maximum Plasma Concentration (Tmax) of TMC310911 | Day 14 | 3.00 hours |
| TMC310911/Rtv 150/100 mg Twice Daily | Time to Reach the Maximum Plasma Concentration (Tmax) of TMC310911 | Day 1 | 5.00 hours |
| TMC310911/Rtv 300/100 mg Twice Daily | Time to Reach the Maximum Plasma Concentration (Tmax) of TMC310911 | Day 1 | 5.06 hours |
| TMC310911/Rtv 300/100 mg Twice Daily | Time to Reach the Maximum Plasma Concentration (Tmax) of TMC310911 | Day 14 | 3.87 hours |
| TMC310911/Rtv 300/100 mg Once a Day | Time to Reach the Maximum Plasma Concentration (Tmax) of TMC310911 | Day 1 | 5.00 hours |
| TMC310911/Rtv 300/100 mg Once a Day | Time to Reach the Maximum Plasma Concentration (Tmax) of TMC310911 | Day 14 | 3.02 hours |