HIV
Conditions
Keywords
Treatment Experienced, Treatment Naive
Brief summary
To assess the viral load response, safety, tolerability and pharmacokinetics of multiple oral doses of PF 00232798 in HIV-positive patient volunteers.
Interventions
DRUGPF-00232798
Solution, 20 mg. once daily, 10 days
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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 patients between the ages of 18 and 55 years inclusive. * Patients with CCR5 tropic virus as determined by the Monogram PhenoSense Entry assay.
Exclusion criteria
* Patients who have received any experimental drug within the past four months (prior to the first dosing day of the study) or who have previously received another CCR5 antagonist. * Patients with evidence of decompensated liver disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Log 10-transformed Human Immunodeficiency Virus (HIV) Viral Load at Day 11 | Baseline, Day 11 | Viral load was determined using the Roche COBAS Taqman HIV-1 assay with a lower limit of detection of 40 copies per milliliter (copies/mL). Samples with an initial reading of less than 1,000,000 copies/mL were diluted into range and re-assayed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Day 1 up to Day 25 | The time to rebound of viral load was calculated as the time from the last dose to the time of the first occasion at which the viral load was greater than the baseline value. Results are reported for number of participants who rebound within specified days from last dose and who did not rebound up to Day 25. |
| Maximum Observed Plasma Concentration (Cmax) | 0 hour (pre-dose) on Day 1 to 9; 0 hour (pre-dose), 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 10; Day 12, 13, 15 morning | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0 hour (pre-dose) on Day 1 to 9; 0 hour (pre-dose), 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 10; Day 12, 13, 15 morning | — |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | 0 hour (pre-dose), 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 10 | AUCtau= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to the time end of dosing interval (24 hours post-dose). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Viral Tropism and Resistance | Screening, pre-dose on Day 1; Day 11, 25 | Virus tropism was determined using the Monogram PhenoSense Entry assay; standard Trofile tropisim assay was used for Stage 1 and enhanced sensitivity Trofile tropisim assay was used for Stage 2. |
| Number of Participants With Chemokine Receptor 5 (CCR5) Delta 32 Genotyping and Immunophenotyping | Pre-dose on Day 1 | CCR5 Delta 32 genotyping and immunophenotyping was to be done to assess CCR5 Delta 32 status, other CCR5 polymorphisms, enzymes involved in drug metabolism and/or drug transport proteins in order to measure the impact of genetic variation with respect to PF-00232798 in case any unusual patterns of response or an unexplained excess of adverse events occurred. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PF-00232798 5 mg Participants received PF-00232798 5 milligram (mg) oral solution once daily up to Day 10 and were followed up to Day 25 in Stage 1. | 6 |
| PF-00232798 20 mg Participants received PF-00232798 20 mg oral solution once daily up to Day 10 and were followed up to Day 25 in Stage 1. | 6 |
| PF-00232798 40 mg Participants received PF-00232798 40 mg oral solution once daily up to Day 10 and were followed up to Day 25 in Stage 2. | 8 |
| PF-00232798 150 mg Participants received PF-00232798 150 mg oral solution once daily up to Day 10 and were followed up to Day 25 in Stage 1. | 6 |
| PF-00232798 300 mg Participants received PF-00232798 300 mg oral solution once daily up to Day 10 and were followed up to Day 25 in Stage 2. | 8 |
| PF-00232798 400mg Participants received PF-00232798 400 mg oral solution once daily up to Day 10 and were followed up to Day 25 in Stage 2. | 7 |
| Placebo Participants received placebo matched to PF-00232798 oral solution once daily up to Day 10 and were followed up to Day 25 in Stage 1. | 2 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Stage 1 (25 Days) | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | PF-00232798 300 mg | PF-00232798 400mg | Placebo | Total | PF-00232798 5 mg | PF-00232798 20 mg | PF-00232798 40 mg | PF-00232798 150 mg |
|---|---|---|---|---|---|---|---|---|
| Age Continuous | 36.1 years STANDARD_DEVIATION 9.6 | 32.9 years STANDARD_DEVIATION 5 | 29 years STANDARD_DEVIATION 5.7 | 35.2 years STANDARD_DEVIATION 7.8 | 31.5 years STANDARD_DEVIATION 8.9 | 39.8 years STANDARD_DEVIATION 8.5 | 36.5 years STANDARD_DEVIATION 5.4 | 36.2 years STANDARD_DEVIATION 9.1 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 2 Participants | 43 Participants | 6 Participants | 6 Participants | 8 Participants | 6 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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 6 | 6 / 6 | 7 / 8 | 5 / 6 | 6 / 8 | 3 / 7 | 2 / 2 |
| serious Total, serious adverse events | 0 / 6 | 1 / 6 | 0 / 8 | 0 / 6 | 0 / 8 | 1 / 7 | 0 / 2 |
Outcome results
Primary
Change From Baseline in Log 10-transformed Human Immunodeficiency Virus (HIV) Viral Load at Day 11
Viral load was determined using the Roche COBAS Taqman HIV-1 assay with a lower limit of detection of 40 copies per milliliter (copies/mL). Samples with an initial reading of less than 1,000,000 copies/mL were diluted into range and re-assayed.
Time frame: Baseline, Day 11
Population: Pharmacodynamic population included all participants who were randomized, treated and had at least 1 post-dose HIV viral load measurement in the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-00232798 5 mg | Change From Baseline in Log 10-transformed Human Immunodeficiency Virus (HIV) Viral Load at Day 11 | Change at Day 11 | -0.253 log10 copies/mL | Standard Deviation 0.3308 |
| PF-00232798 5 mg | Change From Baseline in Log 10-transformed Human Immunodeficiency Virus (HIV) Viral Load at Day 11 | Baseline | 4.692 log10 copies/mL | Standard Deviation 0.3075 |
| PF-00232798 20 mg | Change From Baseline in Log 10-transformed Human Immunodeficiency Virus (HIV) Viral Load at Day 11 | Baseline | 4.338 log10 copies/mL | Standard Deviation 0.4753 |
| PF-00232798 20 mg | Change From Baseline in Log 10-transformed Human Immunodeficiency Virus (HIV) Viral Load at Day 11 | Change at Day 11 | -0.687 log10 copies/mL | Standard Deviation 0.426 |
| PF-00232798 40 mg | Change From Baseline in Log 10-transformed Human Immunodeficiency Virus (HIV) Viral Load at Day 11 | Change at Day 11 | -0.916 log10 copies/mL | Standard Deviation 0.4267 |
| PF-00232798 40 mg | Change From Baseline in Log 10-transformed Human Immunodeficiency Virus (HIV) Viral Load at Day 11 | Baseline | 4.306 log10 copies/mL | Standard Deviation 0.8241 |
| PF-00232798 150 mg | Change From Baseline in Log 10-transformed Human Immunodeficiency Virus (HIV) Viral Load at Day 11 | Baseline | 4.483 log10 copies/mL | Standard Deviation 0.4322 |
| PF-00232798 150 mg | Change From Baseline in Log 10-transformed Human Immunodeficiency Virus (HIV) Viral Load at Day 11 | Change at Day 11 | -1.325 log10 copies/mL | Standard Deviation 0.3887 |
| PF-00232798 300 mg | Change From Baseline in Log 10-transformed Human Immunodeficiency Virus (HIV) Viral Load at Day 11 | Change at Day 11 | -1.546 log10 copies/mL | Standard Deviation 0.3028 |
| PF-00232798 300 mg | Change From Baseline in Log 10-transformed Human Immunodeficiency Virus (HIV) Viral Load at Day 11 | Baseline | 4.315 log10 copies/mL | Standard Deviation 0.612 |
| PF-00232798 400 mg | Change From Baseline in Log 10-transformed Human Immunodeficiency Virus (HIV) Viral Load at Day 11 | Baseline | 4.715 log10 copies/mL | Standard Deviation 0.3153 |
| PF-00232798 400 mg | Change From Baseline in Log 10-transformed Human Immunodeficiency Virus (HIV) Viral Load at Day 11 | Change at Day 11 | -1.492 log10 copies/mL | Standard Deviation 0.5103 |
| Placebo | Change From Baseline in Log 10-transformed Human Immunodeficiency Virus (HIV) Viral Load at Day 11 | Change at Day 11 | -0.135 log10 copies/mL | Standard Deviation 0.0089 |
| Placebo | Change From Baseline in Log 10-transformed Human Immunodeficiency Virus (HIV) Viral Load at Day 11 | Baseline | 4.482 log10 copies/mL | Standard Deviation 0.98 |
Secondary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
AUCtau= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to the time end of dosing interval (24 hours post-dose).
Time frame: 0 hour (pre-dose), 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 10
Population: Pharmacokinetic parameter analysis population included all participants who were randomized, treated and had at least 1 of the pharmacokinetic parameters of interest in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-00232798 5 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | 265.3 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 181.46 |
| PF-00232798 20 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | 1157.4 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 884.12 |
| PF-00232798 40 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | 2945.1 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 1548.47 |
| PF-00232798 150 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | 17319.1 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 7529.14 |
| PF-00232798 300 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | 28347.9 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 5435.54 |
| PF-00232798 400 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | 41027.3 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 20326.95 |
Secondary
Maximum Observed Plasma Concentration (Cmax)
Time frame: 0 hour (pre-dose) on Day 1 to 9; 0 hour (pre-dose), 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 10; Day 12, 13, 15 morning
Population: Pharmacokinetic parameter analysis population included all participants who were randomized, treated and had at least 1 of the pharmacokinetic parameters of interest in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-00232798 5 mg | Maximum Observed Plasma Concentration (Cmax) | 25.21 nanogram per milliliter (ng/mL) | Standard Deviation 13.964 |
| PF-00232798 20 mg | Maximum Observed Plasma Concentration (Cmax) | 185.57 nanogram per milliliter (ng/mL) | Standard Deviation 268.401 |
| PF-00232798 40 mg | Maximum Observed Plasma Concentration (Cmax) | 379.27 nanogram per milliliter (ng/mL) | Standard Deviation 239.376 |
| PF-00232798 150 mg | Maximum Observed Plasma Concentration (Cmax) | 2675.57 nanogram per milliliter (ng/mL) | Standard Deviation 860.86 |
| PF-00232798 300 mg | Maximum Observed Plasma Concentration (Cmax) | 3793.01 nanogram per milliliter (ng/mL) | Standard Deviation 285.845 |
| PF-00232798 400 mg | Maximum Observed Plasma Concentration (Cmax) | 4802.57 nanogram per milliliter (ng/mL) | Standard Deviation 2025.429 |
Secondary
Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load
The time to rebound of viral load was calculated as the time from the last dose to the time of the first occasion at which the viral load was greater than the baseline value. Results are reported for number of participants who rebound within specified days from last dose and who did not rebound up to Day 25.
Time frame: Day 1 up to Day 25
Population: Pharmacodynamic population included all participants who were randomized, treated and had at least 1 post-dose HIV viral load measurement in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-00232798 5 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 3 days | 1 participants |
| PF-00232798 5 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 12 days | 0 participants |
| PF-00232798 5 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 2 days | 1 participants |
| PF-00232798 5 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 15 days | 0 participants |
| PF-00232798 5 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 9 days | 0 participants |
| PF-00232798 5 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | No Rebound | 1 participants |
| PF-00232798 5 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 5 days | 3 participants |
| PF-00232798 20 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 2 days | 0 participants |
| PF-00232798 20 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | No Rebound | 1 participants |
| PF-00232798 20 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 12 days | 2 participants |
| PF-00232798 20 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 3 days | 0 participants |
| PF-00232798 20 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 5 days | 0 participants |
| PF-00232798 20 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 15 days | 1 participants |
| PF-00232798 20 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 9 days | 1 participants |
| PF-00232798 40 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | No Rebound | 6 participants |
| PF-00232798 40 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 12 days | 0 participants |
| PF-00232798 40 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 5 days | 0 participants |
| PF-00232798 40 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 9 days | 2 participants |
| PF-00232798 40 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 15 days | 0 participants |
| PF-00232798 40 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 3 days | 0 participants |
| PF-00232798 40 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 2 days | 0 participants |
| PF-00232798 150 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | No Rebound | 4 participants |
| PF-00232798 150 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 9 days | 1 participants |
| PF-00232798 150 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 12 days | 0 participants |
| PF-00232798 150 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 5 days | 0 participants |
| PF-00232798 150 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 2 days | 0 participants |
| PF-00232798 150 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 3 days | 0 participants |
| PF-00232798 150 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 15 days | 1 participants |
| PF-00232798 300 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 12 days | 0 participants |
| PF-00232798 300 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | No Rebound | 6 participants |
| PF-00232798 300 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 3 days | 0 participants |
| PF-00232798 300 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 5 days | 0 participants |
| PF-00232798 300 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 9 days | 1 participants |
| PF-00232798 300 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 15 days | 1 participants |
| PF-00232798 300 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 2 days | 0 participants |
| PF-00232798 400 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 3 days | 0 participants |
| PF-00232798 400 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 2 days | 0 participants |
| PF-00232798 400 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 5 days | 0 participants |
| PF-00232798 400 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 9 days | 0 participants |
| PF-00232798 400 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 12 days | 1 participants |
| PF-00232798 400 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 15 days | 0 participants |
| PF-00232798 400 mg | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | No Rebound | 6 participants |
| Placebo | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | No Rebound | 1 participants |
| Placebo | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 15 days | 0 participants |
| Placebo | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 5 days | 0 participants |
| Placebo | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 3 days | 0 participants |
| Placebo | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 2 days | 1 participants |
| Placebo | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 12 days | 0 participants |
| Placebo | Number of Participants With Time to Rebound of Human Immunodeficiency Virus (HIV) Viral Load | Rebound within 9 days | 0 participants |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: 0 hour (pre-dose) on Day 1 to 9; 0 hour (pre-dose), 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 10; Day 12, 13, 15 morning
Population: Pharmacokinetic parameter analysis population included all participants who were randomized, treated and had at least 1 of the pharmacokinetic parameters of interest in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-00232798 5 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 3.0000 hours |
| PF-00232798 20 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 1.0330 hours |
| PF-00232798 40 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 4.0000 hours |
| PF-00232798 150 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 3.0415 hours |
| PF-00232798 300 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 2.0000 hours |
| PF-00232798 400 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 2.0000 hours |
Other Pre-specified
Number of Participants With Chemokine Receptor 5 (CCR5) Delta 32 Genotyping and Immunophenotyping
CCR5 Delta 32 genotyping and immunophenotyping was to be done to assess CCR5 Delta 32 status, other CCR5 polymorphisms, enzymes involved in drug metabolism and/or drug transport proteins in order to measure the impact of genetic variation with respect to PF-00232798 in case any unusual patterns of response or an unexplained excess of adverse events occurred.
Time frame: Pre-dose on Day 1
Population: Results for this outcome were not analyzed because there were no unusual patterns of response or an unexplained excess of adverse events that warranted genotyping.
Other Pre-specified
Number of Participants With Viral Tropism and Resistance
Virus tropism was determined using the Monogram PhenoSense Entry assay; standard Trofile tropisim assay was used for Stage 1 and enhanced sensitivity Trofile tropisim assay was used for Stage 2.
Time frame: Screening, pre-dose on Day 1; Day 11, 25
Population: Results for this outcome was not reported because data was collected in individual participant listings, but not summarized for analyses.