HIV-1
Conditions
Brief summary
A phase 2a study to investigate the effects of 7-day monotherapy of UK-453,061 on viral load response in asymptomatic human immunodeficiency virus (HIV) infected subjects, to assess the dose-response relationship, and to assess the pharmacokinetics (PK), safety and tolerability of UK-453,061 in asymptomatic HIV infected subjects.
Interventions
DRUGUK-453,061
Placebo BID, Placebo QD, UK-453,061 10 mg BID, 30 mg BID, 100 mg BID or 500 mg QD for 7 days
Sponsors
ViiV Healthcare
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Asymptomatic HIV-1 infected male and patients aged 18-55 years inclusive. * Patients with virus not containing NNRTI resistant mutations as determined by the VircoGEN virtual phenotyping essay.
Exclusion criteria
* Patients with a CD4 count less than 250 cells/mm3. * Patients whose HIV infection has been diagnosed less than 3 months prior to screening, or for whom there is evidence of recent seroconversion. * Patients with an HIV viral load less than 5000 copies/ml using RT-PCR(Roche Amplicor v1.5).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Human Immunodeficiency Virus-1 (HIV-1) Viral Load at Day 8 | Baseline, Day 8 | Change from baseline in log 10-transformed plasma viral load(Human Immunodeficiency Virus-1 Ribonucleic Acid\[HIV-1 RNA\]) levels(log10 copies/milliliter\[copies/mL\])reported.Viral load determined using reverse transcriptase-polymerase chain reaction(RT-PCR) assay with standard lower limit of detection(LLOD) 400 copies/mL.For samples with reading less than (\<)400 copies/mL,assay repeated using ultra sensitive method with LLOD of 50 copies/mL.Values below limit of quantification(LOQ) 50 copies/mL set to 50 copies/mL.Baseline was mean of three pre-dose values taken at screening,randomization,Day 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Day 8 up to Follow-up (Day 38 to 40 [31 to 33 days post-last dose]) | Time to rebound of viral load was defined as time from the last dose (Day 8) to the time of the first occasion at which the viral load was greater than baseline value. Number of participants with rebound of viral load at specified number of days after last dose (day 8) was reported. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to End of Dosing Interval at Steady State (AUCtau,ss) | 0 (pre-dose), 1, 2, 3, 4, 6, 12 hours post-dose; additional 24 hours post-dose for once daily regimen on Day 8 | AUCtau = Area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the dosing interval (tau), the dosing interval was 12 hours for twice daily regimen and 24 hours for once daily regimen. |
| Maximum Observed Plasma Concentration at Steady State (Cmax,ss) | 0 (pre-dose), 1, 2, 3, 4, 6, 12 hours post-dose; additional 24 hours post-dose for once daily regimen on Day 8 | — |
| Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) | 0 (pre-dose), 1, 2, 3, 4, 6, 12 hours post-dose; additional 24 hours post-dose for once daily regimen on Day 8 | — |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| UK-453,061 10 mg Twice Daily (Stage 1) UK-453,061 10 milligram (mg) suspension orally twice daily for 7 days and as single morning dose on Day 8 in Stage 1. | 6 |
| UK-453,061 30 mg Twice Daily (Stage 1) UK-453,061 30 mg suspension orally twice daily for 7 days and as single morning dose on Day 8 in Stage 1. | 6 |
| UK-453,061 100 mg Twice Daily (Stage 1) UK-453,061 100 mg suspension orally twice daily for 7 days and as single morning dose on Day 8 in Stage 1. | 6 |
| UK-453,061 500 mg Once Daily (Stage 1) UK-453,061 500 mg suspension orally once daily for 8 days in Stage 1. | 6 |
| UK-453,061 750 mg Once Daily (Stage 2) Three UK-453,061 250 mg tablets, equivalent to 750 mg UK-453,061, along with 2 placebo tablets matched to UK-453,061 50 mg tablet orally once daily for 8 days in Stage 2. | 6 |
| UK-453,061 500 mg Twice Daily (Stage 2) Two UK-453,061 250 mg tablets, equivalent to 500 mg UK-453,061, along with 1 placebo tablet matched to UK-453,061 250 mg tablet and 2 placebo tablets matched to UK-453,061 50 mg tablet orally twice daily for 7 days and as single morning dose on Day 8 in Stage 2. | 6 |
| UK-453,061 100 mg Once Daily (Stage 2) Two UK-453,061 50 mg tablets, equivalent to 100 mg UK-453,061, along with 3 placebo tablets matched to UK-453,061 250 mg tablet orally once daily for 8 days in Stage 2. | 6 |
| Placebo Placebo matched to UK-453,061 suspension orally once or twice daily for 7 days and as single morning dose on Day 8 in Stage 1 or 3 placebo tablets matched to UK-453,061 250 mg tablet along with 2 placebo tablets matched to UK-453,061 50 mg tablet orally once or twice daily for 7 days and as single morning dose on Day 8 in Stage 2. | 6 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Stage 1 | Randomized but not Treated | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | UK-453,061 10 mg Twice Daily (Stage 1) | UK-453,061 30 mg Twice Daily (Stage 1) | UK-453,061 100 mg Twice Daily (Stage 1) | UK-453,061 500 mg Once Daily (Stage 1) | UK-453,061 750 mg Once Daily (Stage 2) | UK-453,061 500 mg Twice Daily (Stage 2) | UK-453,061 100 mg Once Daily (Stage 2) | Placebo | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | 38.8 years STANDARD_DEVIATION 8.4 | 38.2 years STANDARD_DEVIATION 8.6 | 33.5 years STANDARD_DEVIATION 8.6 | 41.7 years STANDARD_DEVIATION 4.1 | 29.2 years STANDARD_DEVIATION 7.9 | 40.3 years STANDARD_DEVIATION 7.5 | 37.0 years STANDARD_DEVIATION 8.5 | 33.8 years STANDARD_DEVIATION 8 | 36.6 years STANDARD_DEVIATION 8.2 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 6 | 5 / 6 | 5 / 6 | 5 / 6 | 6 / 6 | 6 / 6 | 3 / 6 | 4 / 6 |
| serious Total, serious adverse events | 0 / 6 | 1 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Change From Baseline in Human Immunodeficiency Virus-1 (HIV-1) Viral Load at Day 8
Change from baseline in log 10-transformed plasma viral load(Human Immunodeficiency Virus-1 Ribonucleic Acid\[HIV-1 RNA\]) levels(log10 copies/milliliter\[copies/mL\])reported.Viral load determined using reverse transcriptase-polymerase chain reaction(RT-PCR) assay with standard lower limit of detection(LLOD) 400 copies/mL.For samples with reading less than (\<)400 copies/mL,assay repeated using ultra sensitive method with LLOD of 50 copies/mL.Values below limit of quantification(LOQ) 50 copies/mL set to 50 copies/mL.Baseline was mean of three pre-dose values taken at screening,randomization,Day 1.
Time frame: Baseline, Day 8
Population: Per protocol pharmacodynamic analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose viral load measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UK-453,061 10 mg Twice Daily (Stage 1) | Change From Baseline in Human Immunodeficiency Virus-1 (HIV-1) Viral Load at Day 8 | Baseline | 4.57 log10 copies/mL | Standard Deviation 0.33 |
| UK-453,061 10 mg Twice Daily (Stage 1) | Change From Baseline in Human Immunodeficiency Virus-1 (HIV-1) Viral Load at Day 8 | Change at Day 8 | -0.30 log10 copies/mL | Standard Deviation 0.2 |
| UK-453,061 30 mg Twice Daily (Stage 1) | Change From Baseline in Human Immunodeficiency Virus-1 (HIV-1) Viral Load at Day 8 | Baseline | 4.39 log10 copies/mL | Standard Deviation 0.48 |
| UK-453,061 30 mg Twice Daily (Stage 1) | Change From Baseline in Human Immunodeficiency Virus-1 (HIV-1) Viral Load at Day 8 | Change at Day 8 | -0.78 log10 copies/mL | Standard Deviation 0.45 |
| UK-453,061 100 mg Twice Daily (Stage 1) | Change From Baseline in Human Immunodeficiency Virus-1 (HIV-1) Viral Load at Day 8 | Baseline | 4.41 log10 copies/mL | Standard Deviation 0.27 |
| UK-453,061 100 mg Twice Daily (Stage 1) | Change From Baseline in Human Immunodeficiency Virus-1 (HIV-1) Viral Load at Day 8 | Change at Day 8 | -1.33 log10 copies/mL | Standard Deviation 0.38 |
| UK-453,061 500 mg Once Daily (Stage 1) | Change From Baseline in Human Immunodeficiency Virus-1 (HIV-1) Viral Load at Day 8 | Baseline | 4.38 log10 copies/mL | Standard Deviation 0.17 |
| UK-453,061 500 mg Once Daily (Stage 1) | Change From Baseline in Human Immunodeficiency Virus-1 (HIV-1) Viral Load at Day 8 | Change at Day 8 | -1.67 log10 copies/mL | Standard Deviation 0.19 |
| UK-453,061 750 mg Once Daily (Stage 2) | Change From Baseline in Human Immunodeficiency Virus-1 (HIV-1) Viral Load at Day 8 | Baseline | 4.65 log10 copies/mL | Standard Deviation 0.46 |
| UK-453,061 750 mg Once Daily (Stage 2) | Change From Baseline in Human Immunodeficiency Virus-1 (HIV-1) Viral Load at Day 8 | Change at Day 8 | -1.79 log10 copies/mL | Standard Deviation 0.32 |
| UK-453,061 500 mg Twice Daily (Stage 2) | Change From Baseline in Human Immunodeficiency Virus-1 (HIV-1) Viral Load at Day 8 | Baseline | 4.55 log10 copies/mL | Standard Deviation 0.45 |
| UK-453,061 500 mg Twice Daily (Stage 2) | Change From Baseline in Human Immunodeficiency Virus-1 (HIV-1) Viral Load at Day 8 | Change at Day 8 | -1.62 log10 copies/mL | Standard Deviation 0.22 |
| UK-453,061 100 mg Once Daily (Stage 2) | Change From Baseline in Human Immunodeficiency Virus-1 (HIV-1) Viral Load at Day 8 | Change at Day 8 | -0.92 log10 copies/mL | Standard Deviation 0.38 |
| UK-453,061 100 mg Once Daily (Stage 2) | Change From Baseline in Human Immunodeficiency Virus-1 (HIV-1) Viral Load at Day 8 | Baseline | 4.70 log10 copies/mL | Standard Deviation 0.33 |
| Placebo | Change From Baseline in Human Immunodeficiency Virus-1 (HIV-1) Viral Load at Day 8 | Baseline | 4.57 log10 copies/mL | Standard Deviation 0.49 |
| Placebo | Change From Baseline in Human Immunodeficiency Virus-1 (HIV-1) Viral Load at Day 8 | Change at Day 8 | 0.01 log10 copies/mL | Standard Deviation 0.16 |
Secondary
Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load
Time to rebound of viral load was defined as time from the last dose (Day 8) to the time of the first occasion at which the viral load was greater than baseline value. Number of participants with rebound of viral load at specified number of days after last dose (day 8) was reported.
Time frame: Day 8 up to Follow-up (Day 38 to 40 [31 to 33 days post-last dose])
Population: Per protocol pharmacodynamic analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose viral load measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| UK-453,061 10 mg Twice Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 31 to 33 days (follow-up) | 1 participants |
| UK-453,061 10 mg Twice Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 2 days | 0 participants |
| UK-453,061 10 mg Twice Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 4 days | 2 participants |
| UK-453,061 10 mg Twice Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 7 days | 2 participants |
| UK-453,061 10 mg Twice Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 21 days | 0 participants |
| UK-453,061 10 mg Twice Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 13 days | 1 participants |
| UK-453,061 30 mg Twice Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 7 days | 1 participants |
| UK-453,061 30 mg Twice Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 2 days | 1 participants |
| UK-453,061 30 mg Twice Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 13 days | 2 participants |
| UK-453,061 30 mg Twice Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 31 to 33 days (follow-up) | 0 participants |
| UK-453,061 30 mg Twice Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 4 days | 1 participants |
| UK-453,061 30 mg Twice Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 21 days | 0 participants |
| UK-453,061 100 mg Twice Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 21 days | 0 participants |
| UK-453,061 100 mg Twice Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 7 days | 1 participants |
| UK-453,061 100 mg Twice Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 4 days | 0 participants |
| UK-453,061 100 mg Twice Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 13 days | 4 participants |
| UK-453,061 100 mg Twice Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 31 to 33 days (follow-up) | 0 participants |
| UK-453,061 100 mg Twice Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 2 days | 0 participants |
| UK-453,061 500 mg Once Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 21 days | 1 participants |
| UK-453,061 500 mg Once Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 2 days | 0 participants |
| UK-453,061 500 mg Once Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 4 days | 0 participants |
| UK-453,061 500 mg Once Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 7 days | 0 participants |
| UK-453,061 500 mg Once Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 13 days | 3 participants |
| UK-453,061 500 mg Once Daily (Stage 1) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 31 to 33 days (follow-up) | 1 participants |
| UK-453,061 750 mg Once Daily (Stage 2) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 21 days | 0 participants |
| UK-453,061 750 mg Once Daily (Stage 2) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 4 days | 0 participants |
| UK-453,061 750 mg Once Daily (Stage 2) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 31 to 33 days (follow-up) | 1 participants |
| UK-453,061 750 mg Once Daily (Stage 2) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 2 days | 0 participants |
| UK-453,061 750 mg Once Daily (Stage 2) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 13 days | 3 participants |
| UK-453,061 750 mg Once Daily (Stage 2) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 7 days | 0 participants |
| UK-453,061 500 mg Twice Daily (Stage 2) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 7 days | 0 participants |
| UK-453,061 500 mg Twice Daily (Stage 2) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 13 days | 1 participants |
| UK-453,061 500 mg Twice Daily (Stage 2) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 4 days | 0 participants |
| UK-453,061 500 mg Twice Daily (Stage 2) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 21 days | 1 participants |
| UK-453,061 500 mg Twice Daily (Stage 2) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 2 days | 0 participants |
| UK-453,061 500 mg Twice Daily (Stage 2) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 31 to 33 days (follow-up) | 1 participants |
| UK-453,061 100 mg Once Daily (Stage 2) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 13 days | 0 participants |
| UK-453,061 100 mg Once Daily (Stage 2) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 21 days | 1 participants |
| UK-453,061 100 mg Once Daily (Stage 2) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 2 days | 0 participants |
| UK-453,061 100 mg Once Daily (Stage 2) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 7 days | 0 participants |
| UK-453,061 100 mg Once Daily (Stage 2) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 31 to 33 days (follow-up) | 1 participants |
| UK-453,061 100 mg Once Daily (Stage 2) | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 4 days | 1 participants |
| Placebo | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 13 days | 0 participants |
| Placebo | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 7 days | 1 participants |
| Placebo | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 31 to 33 days (follow-up) | 1 participants |
| Placebo | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 21 days | 0 participants |
| Placebo | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 2 days | 2 participants |
| Placebo | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | 4 days | 0 participants |
Other Pre-specified
Area Under the Curve From Time Zero to End of Dosing Interval at Steady State (AUCtau,ss)
AUCtau = Area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the dosing interval (tau), the dosing interval was 12 hours for twice daily regimen and 24 hours for once daily regimen.
Time frame: 0 (pre-dose), 1, 2, 3, 4, 6, 12 hours post-dose; additional 24 hours post-dose for once daily regimen on Day 8
Population: Per protocol pharmacokinetic analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose pharmacokinetic concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| UK-453,061 10 mg Twice Daily (Stage 1) | Area Under the Curve From Time Zero to End of Dosing Interval at Steady State (AUCtau,ss) | 47.2 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 21.87 |
| UK-453,061 30 mg Twice Daily (Stage 1) | Area Under the Curve From Time Zero to End of Dosing Interval at Steady State (AUCtau,ss) | 150.0 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 51.57 |
| UK-453,061 100 mg Twice Daily (Stage 1) | Area Under the Curve From Time Zero to End of Dosing Interval at Steady State (AUCtau,ss) | 686.7 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 378.56 |
| UK-453,061 500 mg Once Daily (Stage 1) | Area Under the Curve From Time Zero to End of Dosing Interval at Steady State (AUCtau,ss) | 3543.5 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 818.85 |
| UK-453,061 750 mg Once Daily (Stage 2) | Area Under the Curve From Time Zero to End of Dosing Interval at Steady State (AUCtau,ss) | 6530.1 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 963.97 |
| UK-453,061 500 mg Twice Daily (Stage 2) | Area Under the Curve From Time Zero to End of Dosing Interval at Steady State (AUCtau,ss) | 4719.4 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 744.83 |
| UK-453,061 100 mg Once Daily (Stage 2) | Area Under the Curve From Time Zero to End of Dosing Interval at Steady State (AUCtau,ss) | 863.1 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 260.83 |
Other Pre-specified
Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
Time frame: 0 (pre-dose), 1, 2, 3, 4, 6, 12 hours post-dose; additional 24 hours post-dose for once daily regimen on Day 8
Population: Per protocol pharmacokinetic analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose pharmacokinetic concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| UK-453,061 10 mg Twice Daily (Stage 1) | Maximum Observed Plasma Concentration at Steady State (Cmax,ss) | 14.6 ng/mL | Standard Deviation 4.5 |
| UK-453,061 30 mg Twice Daily (Stage 1) | Maximum Observed Plasma Concentration at Steady State (Cmax,ss) | 42.6 ng/mL | Standard Deviation 20.31 |
| UK-453,061 100 mg Twice Daily (Stage 1) | Maximum Observed Plasma Concentration at Steady State (Cmax,ss) | 146.6 ng/mL | Standard Deviation 120.07 |
| UK-453,061 500 mg Once Daily (Stage 1) | Maximum Observed Plasma Concentration at Steady State (Cmax,ss) | 490.2 ng/mL | Standard Deviation 248.68 |
| UK-453,061 750 mg Once Daily (Stage 2) | Maximum Observed Plasma Concentration at Steady State (Cmax,ss) | 1245.3 ng/mL | Standard Deviation 560.17 |
| UK-453,061 500 mg Twice Daily (Stage 2) | Maximum Observed Plasma Concentration at Steady State (Cmax,ss) | 979.1 ng/mL | Standard Deviation 247.79 |
| UK-453,061 100 mg Once Daily (Stage 2) | Maximum Observed Plasma Concentration at Steady State (Cmax,ss) | 172.4 ng/mL | Standard Deviation 51.53 |
Other Pre-specified
Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss)
Time frame: 0 (pre-dose), 1, 2, 3, 4, 6, 12 hours post-dose; additional 24 hours post-dose for once daily regimen on Day 8
Population: Per protocol pharmacokinetic analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose pharmacokinetic concentration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| UK-453,061 10 mg Twice Daily (Stage 1) | Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) | 1.0 hrs |
| UK-453,061 30 mg Twice Daily (Stage 1) | Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) | 1.0 hrs |
| UK-453,061 100 mg Twice Daily (Stage 1) | Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) | 2.0 hrs |
| UK-453,061 500 mg Once Daily (Stage 1) | Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) | 3.0 hrs |
| UK-453,061 750 mg Once Daily (Stage 2) | Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) | 2.0 hrs |
| UK-453,061 500 mg Twice Daily (Stage 2) | Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) | 1.5 hrs |
| UK-453,061 100 mg Once Daily (Stage 2) | Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) | 2.0 hrs |