Acute Myelogenous Leukemia, Fungal Infection, Neutropenia
Conditions
Keywords
Antifungal Agents, Anti-Infective Agents
Brief summary
The purpose of this study is: to explore the potential for different dosing strategies of posaconazole oral suspension (POS) to increase plasma levels and to profile the pharmacokinetics of these dosing strategies in patients with compromised gastrointestinal function and at high risk for Invasive Fungal Infection.
Interventions
DRUGPosaconazole
Posaconazole will be used for prophylaxis
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects \>=18 years of age * High risk of poor enteral medication absorption, based on the effects of cytotoxic chemotherapy, as evidenced by, but not limited to, mucositis, nausea, vomiting, and diarrhea, at baseline. * High risk of invasive fungal infection (IFI) based on anticipated or documented prolonged neutropenia (absolute neutrophil count \[ANC\] \<500/mm\^3 \[0.5 x 10\^9/L\]). * Clinical laboratory safety tests within normal limits or clinically acceptable to the investigator or sponsor. * Free of any clinically significant disease (other than the primary hematologic disease) that would interfere with the study evaluations. * Subjects must be willing to give written informed consent and able to adhere to dosing, study visit schedule, and mandatory procedures.
Exclusion criteria
* Female subjects who are pregnant, intend to become pregnant, or are nursing. * Excluded prior treatments. Subjects receiving systemic antifungal therapy (oral, intravenous, or inhaled) for the treatment of proven or probable IFI within 30 days of Enrollment (ie, voriconazole, fluconazole \[FLU\], or itraconazole \[ITZ\]). * Subjects receiving posaconazole for prophylaxis against IFI 10 days prior to enrollment. (Subjects who are receiving either voriconazole or micafungin for prophylaxis against IFI should discontinue those therapies upon enrollment.) * Subjects with moderate or severe liver dysfunction at Baseline, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than two times the upper limit of normal (ULN), or a total bilirubin level greater than two times the ULN. * Subjects who have taken prohibited medications more recently than the indicated washout period prior to Enrollment. * Subjects who must take prohibited medications during the study. * Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study. * Subjects who have used any investigational drugs or biologic agents other than their chemotherapy regimens within 30 days of study entry. * Subjects who are part of the staff personnel directly involved with this study. * Subjects who are a family member of the investigational study staff. * Prior enrollment in this study. * Subjects with a history of hypersensitivity or idiosyncratic reactions to azole agents. * Subjects with Eastern Cooperative Oncology Group (ECOG) performance status \>2 prior to induction chemotherapy for their underlying disease. * Subjects with proven or probable invasive or systemic fungal infection at Baseline. * Subjects with a history of acute lymphoblastic leukemia or chronic myelogenous leukemia without blast crisis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean POS Plasma Concentrations on Days 2, 3, and 8. | Predose (0 hour) and 5 hours postdose on Days 2, 3, and 8 | Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose. |
| Mean POS Plasma Concentrations on Days 8 and 15 Stratified by Randomized Dosing Regimen | Predose (0 hour) and 5 hours postdose on Days 8 and 15 | Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose. |
| Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 3 and ≥/<500 ng/mL on Day 8 | Predose (0 hour) and 5 hours postdose on Days 3 and 8 | Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose. |
| Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 3 and ≥/<700 ng/mL on Day 8 | Predose (0 hour) and 5 hours postdose on Days 3 and 8 | Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose. |
| Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15 | Predose (0 hour) and 5 hours postdose on Days 8 and 15 | Individual mean concentrations calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose. |
| Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15 | Predose (0 hour) and 5 hours postdose on Days 8 and 15 | Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Not Randomized POS 200 mg TID on Days 1-8, administered with food or oral nutritional supplements (participants who discontinued anytime before randomization on Day 8). | 14 |
| POS 200 mg TID Days 1-8 Followed by POS 200 mg TID Days 9-15 POS 200 mg TID on Days 1-8 Followed by POS 200 mg TID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to continue with POS 200 mg TID on Days 9-15). | 21 |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15 POS 200 mg TID on Days 1-8 followed by POS 400 mg BID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg BID on Days 9-15). | 20 |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15 POS 200 mg TID on Days 1-8 followed by POS 400 mg TID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg TID on Days 9-15). | 20 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 9 | 1 | 3 | 2 |
| Overall Study | Protocol Violation | 3 | 0 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Not Randomized | POS 200 mg TID Days 1-8 Followed by POS 200 mg TID Days 9-15 | POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15 | POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 5 Participants | 4 Participants | 1 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 16 Participants | 16 Participants | 19 Participants | 62 Participants |
| Sex: Female, Male Female | 6 Participants | 10 Participants | 11 Participants | 9 Participants | 36 Participants |
| Sex: Female, Male Male | 8 Participants | 11 Participants | 9 Participants | 11 Participants | 39 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 | 73 / 75 | 20 / 21 | 20 / 20 | 20 / 20 |
| serious Total, serious adverse events | 16 / 75 | 3 / 21 | 4 / 20 | 5 / 20 |
Outcome results
Primary
Mean POS Plasma Concentrations on Days 2, 3, and 8.
Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.
Time frame: Predose (0 hour) and 5 hours postdose on Days 2, 3, and 8
Population: Analysis of the primary outcome was done on the Balanced Data Set, defined as all participants with no missing pharmacokinetic data for Days 3, 8, and 15 (n=49). From Days 1 to 8, these 49 participants received 200 mg TID. From Days 9 to 15, these 49 participants were randomized to either 200 mg TID (n=19), 400 mg BID (n=14), or 400 mg TID (n=16).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| POS 200 mg TID Days 1-8 | Mean POS Plasma Concentrations on Days 2, 3, and 8. | Day 8 | 637 ng/mL |
| POS 200 mg TID Days 1-8 | Mean POS Plasma Concentrations on Days 2, 3, and 8. | Day 2 | 230 ng/mL |
| POS 200 mg TID Days 1-8 | Mean POS Plasma Concentrations on Days 2, 3, and 8. | Day 3 | 346 ng/mL |
Primary
Mean POS Plasma Concentrations on Days 8 and 15 Stratified by Randomized Dosing Regimen
Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.
Time frame: Predose (0 hour) and 5 hours postdose on Days 8 and 15
Population: Analysis of the primary outcome was done on the Balanced Data Set, defined as all participants with no missing pharmacokinetic data for Days 3, 8, and 15 (n=49). From Days 1 to 8, these 49 participants received 200 mg TID. From Days 9 to 15, these 49 participants were randomized to either 200 mg TID (n=19), 400 mg BID (n=14), or 400 mg TID (n=16).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| POS 200 mg TID Days 1-8 | Mean POS Plasma Concentrations on Days 8 and 15 Stratified by Randomized Dosing Regimen | Day 8 | 620 ng/mL |
| POS 200 mg TID Days 1-8 | Mean POS Plasma Concentrations on Days 8 and 15 Stratified by Randomized Dosing Regimen | Day 15 | 660 ng/mL |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15 | Mean POS Plasma Concentrations on Days 8 and 15 Stratified by Randomized Dosing Regimen | Day 8 | 849 ng/mL |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15 | Mean POS Plasma Concentrations on Days 8 and 15 Stratified by Randomized Dosing Regimen | Day 15 | 930 ng/mL |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15 | Mean POS Plasma Concentrations on Days 8 and 15 Stratified by Randomized Dosing Regimen | Day 8 | 473 ng/mL |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15 | Mean POS Plasma Concentrations on Days 8 and 15 Stratified by Randomized Dosing Regimen | Day 15 | 671 ng/mL |
Primary
Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 3 and ≥/<500 ng/mL on Day 8
Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.
Time frame: Predose (0 hour) and 5 hours postdose on Days 3 and 8
Population: Analysis of the primary outcome was done on the Balanced Data Set, defined as all participants with no missing pharmacokinetic data for Days 3, 8, and 15 (n=49). From Days 1 to 8, these 49 participants received 200 mg TID. From Days 9 to 15, these 49 participants were randomized to either 200 mg TID (n=19), 400 mg BID (n=14), or 400 mg TID (n=16).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 3 and ≥/<500 ng/mL on Day 8 | Day 3 <250 ng/mL and Day 8 <500 ng/mL | 17 Participants |
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 3 and ≥/<500 ng/mL on Day 8 | Day 3 <250 ng/mL and Day 8 ≥500 ng/mL | 2 Participants |
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 3 and ≥/<500 ng/mL on Day 8 | Total Day 3 <250 ng/mL | 19 Participants |
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 3 and ≥/<500 ng/mL on Day 8 | Day 3 ≥250 ng/mL and Day 8 <500 ng/mL | 8 Participants |
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 3 and ≥/<500 ng/mL on Day 8 | Day 3 ≥250 ng/mL and Day 8 ≥500 ng/mL | 22 Participants |
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 3 and ≥/<500 ng/mL on Day 8 | Total Day 3 ≥250 ng/mL | 30 Participants |
Primary
Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15
Individual mean concentrations calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.
Time frame: Predose (0 hour) and 5 hours postdose on Days 8 and 15
Population: Analysis of the primary outcome was done on the Balanced Data Set, defined as all participants with no missing pharmacokinetic data for Days 3, 8, and 15 (n=49). From Days 1 to 8, these 49 participants received 200 mg TID. From Days 9 to 15, these 49 participants were randomized to either 200 mg TID (n=19), 400 mg BID (n=14), or 400 mg TID (n=16).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15 | Day 8 <250 ng/mL and Day 15 <500 ng/mL | 3 Participants |
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15 | Day 8 <250 ng/mL and Day 15 ≥500 ng/mL | 2 Participants |
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15 | Total Day 8 <250 ng/mL | 5 Participants |
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15 | Day 8 ≥250 ng/mL and Day 15 <500 ng/mL | 6 Participants |
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15 | Day 8 ≥250 ng/mL and Day 15 ≥500 ng/mL | 8 Participants |
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15 | Total Day 8 ≥250 ng/mL | 14 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15 | Total Day 8 ≥250 ng/mL | 11 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15 | Day 8 <250 ng/mL and Day 15 <500 ng/mL | 3 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15 | Day 8 ≥250 ng/mL and Day 15 <500 ng/mL | 0 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15 | Day 8 ≥250 ng/mL and Day 15 ≥500 ng/mL | 11 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15 | Day 8 <250 ng/mL and Day 15 ≥500 ng/mL | 0 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15 | Total Day 8 <250 ng/mL | 3 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15 | Day 8 <250 ng/mL and Day 15 ≥500 ng/mL | 1 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15 | Total Day 8 <250 ng/mL | 4 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15 | Total Day 8 ≥250 ng/mL | 12 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15 | Day 8 ≥250 ng/mL and Day 15 <500 ng/mL | 3 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15 | Day 8 <250 ng/mL and Day 15 <500 ng/mL | 3 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15 | Day 8 ≥250 ng/mL and Day 15 ≥500 ng/mL | 9 Participants |
Primary
Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 3 and ≥/<700 ng/mL on Day 8
Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.
Time frame: Predose (0 hour) and 5 hours postdose on Days 3 and 8
Population: Analysis of the primary outcome was done on the Balanced Data Set, defined as all participants with no missing pharmacokinetic data for Days 3, 8, and 15 (n=49). From Days 1 to 8, these 49 participants received 200 mg TID. From Days 9 to 15, these 49 participants were randomized to either 200 mg TID (n=19), 400 mg BID (n=14), or 400 mg TID (n=16).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 3 and ≥/<700 ng/mL on Day 8 | Day 3 <350 ng/mL and Day 8 <700 ng/mL | 25 Participants |
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 3 and ≥/<700 ng/mL on Day 8 | Day 3 <350 ng/mL and Day 8 ≥700 ng/mL | 3 Participants |
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 3 and ≥/<700 ng/mL on Day 8 | Total Day 3 <350 ng/mL | 28 Participants |
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 3 and ≥/<700 ng/mL on Day 8 | Day 3 ≥350 ng/mL and Day 8 <700 ng/mL | 7 Participants |
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 3 and ≥/<700 ng/mL on Day 8 | Day 3 ≥350 ng/mL and Day 8 ≥700 ng/mL | 14 Participants |
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 3 and ≥/<700 ng/mL on Day 8 | Total Day 3 ≥350 ng/mL | 21 Participants |
Primary
Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15
Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.
Time frame: Predose (0 hour) and 5 hours postdose on Days 8 and 15
Population: Analysis of the primary outcome was done on the Balanced Data Set, defined as all participants with no missing pharmacokinetic data for Days 3, 8, and 15 (n=49). From Days 1 to 8, these 49 participants received 200 mg TID. From Days 9 to 15, these 49 participants were randomized to either 200 mg TID (n=19), 400 mg BID (n=14), or 400 mg TID (n=16).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15 | Total Day 8 ≥350 ng/mL | 13 Participants |
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15 | Total Day 8 <350 ng/mL | 6 Participants |
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15 | Day 8 ≥350 ng/mL and Day 15 ≥700 ng/mL | 7 Participants |
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15 | Day 8 <350 ng/mL and Day 15 <700 ng/mL | 5 Participants |
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15 | Day 8 ≥350 ng/mL and Day 15 <700 ng/mL | 6 Participants |
| POS 200 mg TID Days 1-8 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15 | Day 8 <350 ng/mL and Day 15 ≥700 ng/mL | 1 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15 | Day 8 ≥350 ng/mL and Day 15 <700 ng/mL | 2 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15 | Day 8 ≥350 ng/mL and Day 15 ≥700 ng/mL | 9 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15 | Day 8 <350 ng/mL and Day 15 ≥700 ng/mL | 0 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15 | Total Day 8 ≥350 ng/mL | 11 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15 | Day 8 <350 ng/mL and Day 15 <700 ng/mL | 3 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15 | Total Day 8 <350 ng/mL | 3 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15 | Total Day 8 <350 ng/mL | 7 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15 | Day 8 <350 ng/mL and Day 15 <700 ng/mL | 5 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15 | Day 8 <350 ng/mL and Day 15 ≥700 ng/mL | 2 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15 | Total Day 8 ≥350 ng/mL | 9 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15 | Day 8 ≥350 ng/mL and Day 15 <700 ng/mL | 3 Participants |
| POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15 | Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15 | Day 8 ≥350 ng/mL and Day 15 ≥700 ng/mL | 6 Participants |