Trial Outcomes & Findings for Safety, Tolerability and Pharmacokinetics of BIIB118 (PF-05251749) (NCT NCT02443740)
NCT ID: NCT02443740
Last Updated: 2021-02-17
Results Overview
An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
32 participants
Primary outcome timeframe
For Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3
Results posted on
2021-02-17
Participant Flow
The study consisted of 4 cohorts. Cohort 1 and 2 was a 4 period crossover sequence of PF-05251749 and matching placebo. Cohort 3 was designed to characterize the pharmacokinetic (PK) of PF-05251749 in cerebrospinal fluid (CSF) samples. Cohort 4 was a 2 period crossover sequence of unmilled and milled PF-05251749.
Participant milestones
| Measure |
Cohort 1 PF-05251749: Placebo + 30 mg + 250 mg + 500 mg
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: Placebo, PF-05251749 30 milligram (mg), 250 mg and 500 mg in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state except PF-05251749 500 mg. A washout period of at least 7 days was maintained between each Intervention Period.
|
Cohort 1 PF-05251749: 3 mg + Placebo + 250 mg + 500 mg
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 3 mg, placebo, PF-05251749 250 mg and 500 mg in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state except PF-05251749 500 mg. A washout period of at least 7 days was maintained between each Intervention Period.
|
Cohort 1 PF-05251749: 3 mg + 30 mg + Placebo + 500 mg
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 3 mg, 30 mg, placebo and PF-05251749 500 mg in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state except PF-05251749 500 mg. A washout period of at least 7 days was maintained between each Intervention Period.
|
Cohort 1 PF-05251749: 3 mg + 30 mg + 250 mg + Placebo
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 3 mg, 30 mg, 250 mg and placebo in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state except PF-05251749 500 mg. A washout period of at least 7 days was maintained between each Intervention Period.
|
Cohort 2 PF-05251749: Placebo + 100 mg + 500 mg + 1000 mg
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 placebo, PF-05251749 100 mg, PF-05251749 500 mg, PF-05251749 1000 mg in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period.
|
Cohort 2 PF-05251749: 10 mg + Placebo + 500 mg + 1000 mg
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 10 mg, PF-05251749 placebo, PF-05251749 500 mg, PF-05251749 1000 mg in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period.
|
Cohort 2 PF-05251749: 10 mg + 100 mg + Placebo + 1000 mg
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 10 mg, PF-05251749 100 mg, PF-05251749 placebo, PF-05251749 1000 mg in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period.
|
Cohort 2 PF-05251749: 10 mg + 100 mg + 500 mg + Placebo
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 10 mg, PF-05251749 100 mg, PF-05251749 500 mg, PF-05251749 placebo in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period.
|
Cohort 3 PF-05251749: 500 mg
Participants received a single oral dose of PF-05251749 500 mg suspension on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4 PF-05251749: 500 mg Unmilled + 500 mg Milled
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (2 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 500mg unmilled, PF-05251749 500mg milled in Intervention Period 1 and 2. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period.
|
Cohort 4 PF-05251749: 500 mg Milled + 500 mg Unmilled
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (2 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 500 mg milled, PF-05251749 500 mg unmilled in Intervention Period 1 and 2. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period.
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Intervention Period 1 (3 Days)
STARTED
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2
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Intervention Period 1 (3 Days)
COMPLETED
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6
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Intervention Period 1 (3 Days)
NOT COMPLETED
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Washout Period 1 (7 Days)
STARTED
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Washout Period 1 (7 Days)
COMPLETED
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Washout Period 1 (7 Days)
NOT COMPLETED
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Intervention Period 2 (3 Days)
STARTED
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Intervention Period 2 (3 Days)
COMPLETED
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Intervention Period 2 (3 Days)
NOT COMPLETED
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Washout Period 2 (7 Days)
STARTED
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Washout Period 2 (7 Days)
COMPLETED
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Washout Period 2 (7 Days)
NOT COMPLETED
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Intervention Period 3 (3 Days)
STARTED
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Intervention Period 3 (3 Days)
COMPLETED
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Intervention Period 3 (3 Days)
NOT COMPLETED
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Washout Period 3 (7 Days)
STARTED
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Washout Period 3 (7 Days)
COMPLETED
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Washout Period 3 (7 Days)
NOT COMPLETED
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0
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Intervention Period 4 (3 Days)
STARTED
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Intervention Period 4 (3 Days)
COMPLETED
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Intervention Period 4 (3 Days)
NOT COMPLETED
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0
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Reasons for withdrawal
| Measure |
Cohort 1 PF-05251749: Placebo + 30 mg + 250 mg + 500 mg
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: Placebo, PF-05251749 30 milligram (mg), 250 mg and 500 mg in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state except PF-05251749 500 mg. A washout period of at least 7 days was maintained between each Intervention Period.
|
Cohort 1 PF-05251749: 3 mg + Placebo + 250 mg + 500 mg
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 3 mg, placebo, PF-05251749 250 mg and 500 mg in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state except PF-05251749 500 mg. A washout period of at least 7 days was maintained between each Intervention Period.
|
Cohort 1 PF-05251749: 3 mg + 30 mg + Placebo + 500 mg
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 3 mg, 30 mg, placebo and PF-05251749 500 mg in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state except PF-05251749 500 mg. A washout period of at least 7 days was maintained between each Intervention Period.
|
Cohort 1 PF-05251749: 3 mg + 30 mg + 250 mg + Placebo
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 3 mg, 30 mg, 250 mg and placebo in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state except PF-05251749 500 mg. A washout period of at least 7 days was maintained between each Intervention Period.
|
Cohort 2 PF-05251749: Placebo + 100 mg + 500 mg + 1000 mg
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 placebo, PF-05251749 100 mg, PF-05251749 500 mg, PF-05251749 1000 mg in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period.
|
Cohort 2 PF-05251749: 10 mg + Placebo + 500 mg + 1000 mg
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 10 mg, PF-05251749 placebo, PF-05251749 500 mg, PF-05251749 1000 mg in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period.
|
Cohort 2 PF-05251749: 10 mg + 100 mg + Placebo + 1000 mg
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 10 mg, PF-05251749 100 mg, PF-05251749 placebo, PF-05251749 1000 mg in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period.
|
Cohort 2 PF-05251749: 10 mg + 100 mg + 500 mg + Placebo
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 10 mg, PF-05251749 100 mg, PF-05251749 500 mg, PF-05251749 placebo in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period.
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Cohort 3 PF-05251749: 500 mg
Participants received a single oral dose of PF-05251749 500 mg suspension on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
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Cohort 4 PF-05251749: 500 mg Unmilled + 500 mg Milled
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (2 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 500mg unmilled, PF-05251749 500mg milled in Intervention Period 1 and 2. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period.
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Cohort 4 PF-05251749: 500 mg Milled + 500 mg Unmilled
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (2 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 500 mg milled, PF-05251749 500 mg unmilled in Intervention Period 1 and 2. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period.
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Intervention Period 1 (3 Days)
Adverse Event
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0
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0
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0
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0
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0
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1
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0
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0
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0
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0
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0
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Intervention Period 1 (3 Days)
Protocol Violation
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1
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0
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0
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0
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0
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0
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1
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0
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0
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0
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0
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Intervention Period 1 (3 Days)
Withdrawal by Subject
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0
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0
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0
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0
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0
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1
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0
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0
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0
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0
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0
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Baseline Characteristics
Safety, Tolerability and Pharmacokinetics of BIIB118 (PF-05251749)
Baseline characteristics by cohort
| Measure |
Cohort 1
n=9 Participants
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: Placebo, PF-05251749 30 mg, 250 mg and 500 mg; PF-05251749 3 mg, placebo, PF-05251749 250 mg and 500 mg; PF-05251749 3 mg, 30 mg, placebo and PF-05251749 500 mg; PF-05251749 3 mg, 30 mg, 250 mg and placebo in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state except PF-05251749 500 mg. A washout period of at least 7 days was maintained between each Intervention Period.
|
Cohort 2
n=11 Participants
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 placebo, PF-05251749 100mg, PF-05251749 500mg, PF-05251749 1000mg; PF-05251749 10mg, PF-05251749 placebo, PF-05251749 500mg, PF-05251749 1000mg; PF-05251749 10mg, PF-05251749 100mg, PF-05251749 placebo, PF-05251749 1000mg and PF-05251749 10mg, PF-05251749 100mg, PF-05251749 500mg, PF-05251749 placebo in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period.
|
Cohort 3
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg suspension on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4
n=6 Participants
Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (2 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 500mg unmilled, PF-05251749 500mg milled and PF-05251749 500mg milled, PF-05251749 500mg unmilled in Intervention Period 1 and 2. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period.
|
Total
n=32 Participants
Total of all reporting groups
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|---|---|---|---|---|---|
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Age, Continuous
|
32.7 years
STANDARD_DEVIATION 10.2 • n=5 Participants
|
41.3 years
STANDARD_DEVIATION 6.3 • n=7 Participants
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44.5 years
STANDARD_DEVIATION 6.0 • n=5 Participants
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38.5 years
STANDARD_DEVIATION 11.2 • n=4 Participants
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38.9 years
STANDARD_DEVIATION 9.2 • n=21 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
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0 Participants
n=7 Participants
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0 Participants
n=5 Participants
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0 Participants
n=4 Participants
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0 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
32 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: For Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3Population: Safety analysis set included all participants who received at least 1 dose of study treatment.
An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
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Cohort 2: PF-05251749 100 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
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Cohort 1-2: Placebo
n=15 Participants
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
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Cohort 3: PF-05251749 500 mg CSF
n=6 Participants
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
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|---|---|---|---|---|---|---|---|---|---|---|---|---|
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Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
|
0 participants
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2 participants
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0 participants
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1 participants
|
0 participants
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0 participants
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4 participants
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3 participants
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3 participants
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5 participants
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0 participants
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1 participants
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PRIMARY outcome
Timeframe: Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3Population: Safety analysis set included all participants who received at least 1 dose of study treatment.
Hemoglobin(Hgb),hematocrit,red blood cell(RBC):less than(\<)0.8\*lower limit of normal(LLN), MCV,MCH,MCHC,MPV:\<0.9\*LLN or \>1.1\*upper limit of normal(ULN), platelet:\<0.5\*LLN or \>1.75\*ULN, white blood cell(WBC):\<0.6\*LLNor\>1.5\*ULN, lymphocyte,neutrophil,total neutrophil:\<0.8\*LLN or \>1.2\*ULN,basophil,eosinophil,monocyte:\>1.2\*ULN; PTT, PT:\>1.1\*ULN,Fibrinogen\<0.75\*ULNor\>1.25ULN; total, direct, indirect bilirubin \>1.5\*ULN,aspartate aminotransferase,alanine aminotransferase,gamma-glutamyl transferase,alkaline phosphatase:\> 3.0\*ULN,total protein,albumin:\<0.8\*LLN or \>1.2\*ULN;blood urea nitrogen,creatinine:\>1.3\*ULN,uric acid\>1.2\*ULN;sodium:\<0.95\*LLN or\>1.05\*ULN,potassium,chloride, calcium,magnesium,bicarbonate:\<0.9\*LLN or \>1.1\*ULN, phosphate\<0.8\*LLN or \>1.2\*ULN; glucose \<0.6\*LLN or \>1.5\*ULN,creatine kinase\>2.0\*ULN;urine(specific gravity\<1.003or\>1.030,pH \<4.5or\>8,glucose,ketone,protein,blood/Hgb,bilirubin,leukocyte esterase,crystals\>=1,RBC,WBC \>=20\*ULN,bacteria\>20);CSF (WBC\>=6,RBC\>0,Albumin\>35).
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
n=15 Participants
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
n=6 Participants
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Laboratory Abnormalities
|
3 participants
|
2 participants
|
1 participants
|
2 participants
|
3 participants
|
3 participants
|
4 participants
|
3 participants
|
6 participants
|
5 participants
|
1 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3Population: Safety analysis set included all participants who received at least 1 dose of study treatment.
Criteria for clinically significant change from baseline in vital signs: supine systolic blood pressure (SBP) \<90 millimeter of mercury (mmHg), supine diastolic BP (DBP) \<50 mmHg, supine pulse rate \<40 beats per minute (bpm) or \>120 bpm. Maximum increase or decrease from baseline in supine SBP greater than or equal to (\>=)30 mmHg and maximum increase or decrease from baseline in supine DBP \>=20 mmHg.
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
n=15 Participants
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
n=6 Participants
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3Population: Safety analysis set included all participants who received at least 1 dose of study treatment.
ECG parameters included maximum pulse rate (PR) interval, QRS interval, and corrected QT interval using Fridericia's formula (QTcF). Criteria for abnormal ECG: Maximum PR interval \>=300 milliseconds (msec) or \>=25 percent increase when baseline is \>200 msec and \>=50 percent increase when baseline is less than or equal to (=\<) 200 msec; QRS interval \>=140 msec or \>=50 percent increase from baseline (IFB); and QTcF 30\<=change\<60 or change\>=60 msec increase. The number of participants with abnormal ECG findings are reported.
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
n=15 Participants
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
n=6 Participants
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
3 participants
|
2 participants
|
1 participants
|
0 participants
|
0 participants
|
1 participants
|
PRIMARY outcome
Timeframe: Baseline, Day 1: 2 hours post dosePopulation: Safety analysis set included all participants who received at least 1 dose of study treatment. This outcome measure was not planned to be analyzed in Cohort 3 and 4, as pre-specified in protocol.
The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items \[total range 0 to 100, where each item is ordered so that higher scores indicated more alertness\]), b) contentment (average of 2 items \[total range 0 to 100, where higher scores indicated more contentment\]), and c) calmness (average of 5 items \[total range 0 to 100, where higher scores indicated more calmness\]). Baseline is defined as the last available recording prior to dosing on Day 1 of the first Period.
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
n=15 Participants
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2
Alertness: Baseline
|
63.95 millimeter
Standard Deviation 21.656
|
83.05 millimeter
Standard Deviation 9.176
|
79.12 millimeter
Standard Deviation 21.139
|
74.92 millimeter
Standard Deviation 24.371
|
82.22 millimeter
Standard Deviation 14.773
|
89.98 millimeter
Standard Deviation 7.900
|
81.37 millimeter
Standard Deviation 22.535
|
87.57 millimeter
Standard Deviation 19.500
|
83.47 millimeter
Standard Deviation 14.945
|
—
|
—
|
—
|
|
Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2
Alertness: Change at 2 hours postdose
|
11.48 millimeter
Standard Deviation 15.395
|
8.87 millimeter
Standard Deviation 20.227
|
8.65 millimeter
Standard Deviation 15.615
|
14.62 millimeter
Standard Deviation 23.859
|
2.28 millimeter
Standard Deviation 7.327
|
4.17 millimeter
Standard Deviation 3.247
|
0.30 millimeter
Standard Deviation 9.562
|
-3.40 millimeter
Standard Deviation 10.744
|
7.45 millimeter
Standard Deviation 18.622
|
—
|
—
|
—
|
|
Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2
Calmness: Baseline
|
68.83 millimeter
Standard Deviation 27.518
|
82.83 millimeter
Standard Deviation 10.424
|
84.67 millimeter
Standard Deviation 13.227
|
70.83 millimeter
Standard Deviation 23.962
|
73.58 millimeter
Standard Deviation 19.135
|
79.92 millimeter
Standard Deviation 21.280
|
90.33 millimeter
Standard Deviation 11.206
|
82.83 millimeter
Standard Deviation 19.372
|
80.10 millimeter
Standard Deviation 23.051
|
—
|
—
|
—
|
|
Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2
Calmness: Change at 2 hours postdose
|
9.08 millimeter
Standard Deviation 14.857
|
12.42 millimeter
Standard Deviation 25.305
|
5.08 millimeter
Standard Deviation 5.800
|
2.33 millimeter
Standard Deviation 26.174
|
8.75 millimeter
Standard Deviation 6.594
|
5.42 millimeter
Standard Deviation 5.545
|
3.33 millimeter
Standard Deviation 7.878
|
-10.33 millimeter
Standard Deviation 33.673
|
8.30 millimeter
Standard Deviation 25.787
|
—
|
—
|
—
|
|
Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2
Contentment: Baseline
|
68.10 millimeter
Standard Deviation 26.737
|
83.20 millimeter
Standard Deviation 11.331
|
84.83 millimeter
Standard Deviation 11.542
|
78.03 millimeter
Standard Deviation 18.151
|
85.00 millimeter
Standard Deviation 14.105
|
84.63 millimeter
Standard Deviation 18.600
|
90.50 millimeter
Standard Deviation 9.294
|
89.70 millimeter
Standard Deviation 15.592
|
86.09 millimeter
Standard Deviation 16.013
|
—
|
—
|
—
|
|
Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2
Contentment: Change at 2 hours postdose
|
7.57 millimeter
Standard Deviation 14.995
|
8.20 millimeter
Standard Deviation 21.017
|
5.20 millimeter
Standard Deviation 15.491
|
7.40 millimeter
Standard Deviation 29.055
|
4.90 millimeter
Standard Deviation 4.688
|
1.80 millimeter
Standard Deviation 5.362
|
-0.43 millimeter
Standard Deviation 8.584
|
-0.97 millimeter
Standard Deviation 11.598
|
5.55 millimeter
Standard Deviation 20.253
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 1: 6 hours post dosePopulation: Safety analysis set included all participants who received at least 1 dose of study treatment. This outcome measure was not planned to be analyzed in Cohort 3 and 4, as pre-specified in protocol.
The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items \[total range 0 to 100, where each item is ordered so that higher scores indicated more alertness\]), b) contentment (average of 2 items \[total range 0 to 100, where higher scores indicated more contentment\]), and c) calmness (average of 5 items \[total range 0 to 100, where higher scores indicated more calmness\]). Baseline is defined as the last available recording prior to dosing on Day 1 of the first Period.
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
n=15 Participants
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2
Alertness: Change at 6 hours postdose
|
9.25 millimeter
Standard Deviation 22.935
|
16.85 millimeter
Standard Deviation 16.053
|
12.72 millimeter
Standard Deviation 15.116
|
18.72 millimeter
Standard Deviation 22.991
|
3.43 millimeter
Standard Deviation 6.825
|
-2.50 millimeter
Standard Deviation 18.228
|
-1.07 millimeter
Standard Deviation 10.708
|
-1.00 millimeter
Standard Deviation 8.820
|
5.93 millimeter
Standard Deviation 25.464
|
—
|
—
|
—
|
|
Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2
Calmness: Change at 6 hours postdose
|
6.67 millimeter
Standard Deviation 7.916
|
6.83 millimeter
Standard Deviation 16.549
|
-0.67 millimeter
Standard Deviation 16.136
|
16.00 millimeter
Standard Deviation 13.936
|
2.58 millimeter
Standard Deviation 6.829
|
8.33 millimeter
Standard Deviation 8.542
|
-1.58 millimeter
Standard Deviation 16.209
|
2.17 millimeter
Standard Deviation 2.658
|
8.83 millimeter
Standard Deviation 25.441
|
—
|
—
|
—
|
|
Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2
Contentment: Change at 6 hours postdose
|
7.53 millimeter
Standard Deviation 17.418
|
11.60 millimeter
Standard Deviation 19.555
|
4.80 millimeter
Standard Deviation 9.728
|
12.20 millimeter
Standard Deviation 23.074
|
1.20 millimeter
Standard Deviation 4.746
|
0.80 millimeter
Standard Deviation 9.955
|
0.40 millimeter
Standard Deviation 6.331
|
3.03 millimeter
Standard Deviation 9.063
|
7.51 millimeter
Standard Deviation 19.539
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3: 48 hours post dosePopulation: Safety analysis set included all participants who received at least 1 dose of study treatment. This outcome measure was not planned to be analyzed in Cohort 3 and 4, as pre-specified in protocol.
The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items \[total range 0 to 100, where each item is ordered so that higher scores indicated more alertness\]), b) contentment (average of 2 items \[total range 0 to 100, where higher scores indicated more contentment\]), and c) calmness (average of 5 items \[total range 0 to 100, where higher scores indicated more calmness\]). Baseline is defined as the last available recording prior to dosing on Day 1 of the first Period.
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
n=15 Participants
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2
Alertness: Change at 48 hours postdose
|
15.83 millimeter
Standard Deviation 15.371
|
11.45 millimeter
Standard Deviation 13.703
|
15.80 millimeter
Standard Deviation 14.284
|
20.92 millimeter
Standard Deviation 19.343
|
3.90 millimeter
Standard Deviation 13.966
|
6.08 millimeter
Standard Deviation 7.372
|
6.12 millimeter
Standard Deviation 6.228
|
5.62 millimeter
Standard Deviation 6.576
|
9.67 millimeter
Standard Deviation 12.048
|
—
|
—
|
—
|
|
Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2
Calmness:Change at 48 hours postdose
|
-0.50 millimeter
Standard Deviation 23.791
|
6.17 millimeter
Standard Deviation 26.470
|
5.33 millimeter
Standard Deviation 9.983
|
8.67 millimeter
Standard Deviation 23.920
|
3.00 millimeter
Standard Deviation 5.550
|
-4.83 millimeter
Standard Deviation 20.966
|
-11.75 millimeter
Standard Deviation 25.284
|
10.00 millimeter
Standard Deviation 18.213
|
5.27 millimeter
Standard Deviation 18.547
|
—
|
—
|
—
|
|
Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2
Contentment: Change at 48 hours postdose
|
13.70 millimeter
Standard Deviation 17.876
|
10.77 millimeter
Standard Deviation 16.112
|
6.87 millimeter
Standard Deviation 19.681
|
19.60 millimeter
Standard Deviation 21.045
|
4.00 millimeter
Standard Deviation 2.343
|
2.87 millimeter
Standard Deviation 3.090
|
4.60 millimeter
Standard Deviation 7.859
|
4.97 millimeter
Standard Deviation 5.967
|
7.56 millimeter
Standard Deviation 11.916
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 1: 2 hours post dosePopulation: Safety analysis set included all participants who received at least 1 dose of study treatment. This outcome measure was not planned to be analyzed in Cohort 3 and 4, as pre-specified in protocol.
ESRS is a clinician rated scale to assess parkinsonism,dystonia,dyskinesia,akathisia.The ESRS consists of 4 subscales and 4 clinicians global impressions-severity scales(CGI-S scales):I)a questionnaire of extrapyramidal symptoms or drug-induced movement disorders(a series of 4-point Likert scale questions with 0=Absent and 3=Severe);II)an examination of Parkinsonism and akathisia(7-point Likert scale with 0=Absent,6=extremely severe);III)an examination of dystonia(7-point Likert scale with 0=Absent,6=extremely severe);IV)an examination of dyskinesia(7-point Likert scale with 0=normal,6=most severe);V)toVIII)CGI-S scales(9-point Likert scale with 0=Absent,8=extremely severe)of tardive dyskinesia,parkinsonism,dystonia,akathisia.ESRS-Parkinsonism:total score range:0 to 14 where higher scores indicates greater severity;ESRS-dystonia:total score range:0 to 14 where higher scores indicates greater severity.Change from baseline was only observed in examination of parkinsonism and dystonia.
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
n=15 Participants
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2
Parkinsonism: Baseline
|
0.0 units on a scale
Standard Deviation 0.00
|
0.3 units on a scale
Standard Deviation 0.52
|
0.3 units on a scale
Standard Deviation 0.52
|
0.3 units on a scale
Standard Deviation 0.52
|
0.2 units on a scale
Standard Deviation 0.41
|
0.0 units on a scale
Standard Deviation 0.00
|
0.2 units on a scale
Standard Deviation 0.41
|
0.2 units on a scale
Standard Deviation 0.41
|
0.1 units on a scale
Standard Deviation 0.35
|
—
|
—
|
—
|
|
Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2
Parkinsonism: Change at 2 hours postdose
|
0.0 units on a scale
Standard Deviation 0.00
|
0.2 units on a scale
Standard Deviation 0.75
|
-0.3 units on a scale
Standard Deviation 0.52
|
-0.3 units on a scale
Standard Deviation 0.52
|
0.2 units on a scale
Standard Deviation 0.41
|
0.0 units on a scale
Standard Deviation 0.00
|
-0.2 units on a scale
Standard Deviation 0.41
|
-0.2 units on a scale
Standard Deviation 0.41
|
0.0 units on a scale
Standard Deviation 0.38
|
—
|
—
|
—
|
|
Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2
Dystonia: Baseline
|
0.0 units on a scale
Standard Deviation 0.00
|
0.2 units on a scale
Standard Deviation 0.41
|
0.2 units on a scale
Standard Deviation 0.41
|
0.2 units on a scale
Standard Deviation 0.41
|
0.0 units on a scale
Standard Deviation 0.00
|
0.0 units on a scale
Standard Deviation 0.00
|
0.0 units on a scale
Standard Deviation 0.00
|
0.0 units on a scale
Standard Deviation 0.00
|
0.1 units on a scale
Standard Deviation 0.26
|
—
|
—
|
—
|
|
Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2
Dystonia: Change at 2 hours postdose
|
0.0 units on a scale
Standard Deviation 0.00
|
0.0 units on a scale
Standard Deviation 0.00
|
-0.2 units on a scale
Standard Deviation 0.41
|
-0.2 units on a scale
Standard Deviation 0.41
|
0.0 units on a scale
Standard Deviation 0.00
|
0.0 units on a scale
Standard Deviation 0.00
|
0.0 units on a scale
Standard Deviation 0.00
|
0.0 units on a scale
Standard Deviation 0.00
|
0.0 units on a scale
Standard Deviation 0.00
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 1: 48 hours post dosePopulation: Safety analysis set included all participants who received at least 1 dose of study treatment. This outcome measure was not planned to be analyzed in Cohort 3 and 4, as pre-specified in protocol.
ESRS is a clinician rated scale to assess parkinsonism,dystonia,dyskinesia,akathisia.The ESRS consists of 4 subscales and 4 clinicians global impressions-severity scales(CGI-S scales):I)a questionnaire of extrapyramidal symptoms or drug-induced movement disorders(a series of 4-point Likert scale questions with 0=Absent and 3=Severe);II)an examination of Parkinsonism and akathisia(7-point Likert scale with 0=Absent,6=extremely severe);III)an examination of dystonia(7-point Likert scale with 0=Absent,6=extremely severe);IV)an examination of dyskinesia(7-point Likert scale with 0=normal,6=most severe);V)toVIII)CGI-S scales(9-point Likert scale with 0=Absent,8=extremely severe)of tardive dyskinesia,parkinsonism,dystonia,akathisia.ESRS-Parkinsonism:total score range:0 to 14 where higher scores indicates greater severity;ESRS-dystonia:total score range:0 to 14 where higher scores indicates greater severity.Change from baseline was only observed in examination of parkinsonism and dystonia.
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
n=15 Participants
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2
Parkinsonism:48 hours postdose
|
0.0 units on a scale
Standard Deviation 0.00
|
0.0 units on a scale
Standard Deviation 0.63
|
0.0 units on a scale
Standard Deviation 0.63
|
-0.2 units on a scale
Standard Deviation 0.41
|
0.2 units on a scale
Standard Deviation 0.41
|
0.0 units on a scale
Standard Deviation 0.00
|
-0.2 units on a scale
Standard Deviation 0.41
|
-0.2 units on a scale
Standard Deviation 0.41
|
-0.1 units on a scale
Standard Deviation 0.26
|
—
|
—
|
—
|
|
Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2
Dystonia: 48 hours postdose
|
0.0 units on a scale
Standard Deviation 0.00
|
-0.2 units on a scale
Standard Deviation 0.41
|
-0.2 units on a scale
Standard Deviation 0.41
|
-0.2 units on a scale
Standard Deviation 0.41
|
0.0 units on a scale
Standard Deviation 0.00
|
0.0 units on a scale
Standard Deviation 0.00
|
0.0 units on a scale
Standard Deviation 0.00
|
0.0 units on a scale
Standard Deviation 0.00
|
0.0 units on a scale
Standard Deviation 0.00
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dosePopulation: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period.
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of PF-05251749
|
16.7 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 38
|
173.9 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 33
|
1725 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 39
|
1218 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 33
|
60.08 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 12
|
893.6 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 32
|
3078 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 18
|
4582 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 35
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dosePopulation: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period.
Area under the plasma concentration-time profile from time zero to the time of last quantifiable concentration (Clast ).
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05251749
|
58.95 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 52
|
714.7 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 48
|
6542 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 46
|
14120 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 35
|
281.9 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 19
|
3548 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 27
|
17520 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 23
|
33420 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 36
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dosePopulation: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period.
AUC (0 -∞) = Area under the plasma concentration- time profile from time zero extrapolated to infinite time. It was calculated as AUC last + (C last\*/k el), where C last\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-05251749
|
67.62 ng*hr/mL
Geometric Coefficient of Variation 50
|
729.2 ng*hr/mL
Geometric Coefficient of Variation 48
|
6607 ng*hr/mL
Geometric Coefficient of Variation 47
|
14350 ng*hr/mL
Geometric Coefficient of Variation 35
|
300.8 ng*hr/mL
Geometric Coefficient of Variation 19
|
3623 ng*hr/mL
Geometric Coefficient of Variation 27
|
17910 ng*hr/mL
Geometric Coefficient of Variation 24
|
33990 ng*hr/mL
Geometric Coefficient of Variation 36
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dosePopulation: The PK concentration analysis set included all enrolled participants who were treated and had at least 1 measurable concentration in at least 1 treatment period.
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05251749
|
1.00 hour
Interval 0.5 to 1.03
|
1.00 hour
Interval 0.5 to 1.5
|
1.00 hour
Interval 0.5 to 1.02
|
3.00 hour
Interval 0.5 to 8.0
|
1.00 hour
Interval 1.0 to 1.5
|
1.00 hour
Interval 0.5 to 1.0
|
1.25 hour
Interval 1.0 to 2.0
|
1.00 hour
Interval 1.0 to 4.0
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dosePopulation: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period.
Terminal elimination half-life (t1/2). It was calculated as dividing the natural logarithm to the base e (Log e)\*2/k el, where k el is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Plasma Decay Half-Life (t1/2) of PF-05251749
|
5.255 hour
Standard Deviation 2.5047
|
8.563 hour
Standard Deviation 3.3747
|
7.707 hour
Standard Deviation 2.3957
|
8.400 hour
Standard Deviation 1.1415
|
8.863 hour
Standard Deviation 2.2617
|
9.520 hour
Standard Deviation 2.6104
|
9.513 hour
Standard Deviation 2.1843
|
8.888 hour
Standard Deviation 1.2778
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dosePopulation: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period.
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Apparent Oral Clearance (CL/F) of PF-05251749
|
44.38 liter per hour (L/hr)
Geometric Coefficient of Variation 50
|
41.18 liter per hour (L/hr)
Geometric Coefficient of Variation 48
|
37.87 liter per hour (L/hr)
Geometric Coefficient of Variation 47
|
34.87 liter per hour (L/hr)
Geometric Coefficient of Variation 35
|
33.25 liter per hour (L/hr)
Geometric Coefficient of Variation 19
|
27.60 liter per hour (L/hr)
Geometric Coefficient of Variation 27
|
27.90 liter per hour (L/hr)
Geometric Coefficient of Variation 24
|
29.45 liter per hour (L/hr)
Geometric Coefficient of Variation 36
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dosePopulation: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period.
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Apparent Volume of Distribution (Vz/F) of PF-05251749
|
298.9 Liter
Geometric Coefficient of Variation 37
|
458.5 Liter
Geometric Coefficient of Variation 37
|
396.7 Liter
Geometric Coefficient of Variation 29
|
419.0 Liter
Geometric Coefficient of Variation 34
|
415.1 Liter
Geometric Coefficient of Variation 22
|
365.7 Liter
Geometric Coefficient of Variation 31
|
373.7 Liter
Geometric Coefficient of Variation 18
|
374.4 Liter
Geometric Coefficient of Variation 42
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dosePopulation: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. This outcome measure was not planned to be analyzed for Cohort 1, 2 and 3, as pre-specified in protocol.
Area under the plasma concentration-time profile from time zero to the time of last quantifiable concentration (Clast).
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Milled and Unmilled PF-05251749: Cohort 4
|
12600 ng*hr/mL
Geometric Coefficient of Variation 22
|
19210 ng*hr/mL
Geometric Coefficient of Variation 17
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dosePopulation: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. This outcome measure was not planned to be analyzed for Cohort 1, 2 and 3, as pre-specified in protocol.
AUC (0 -∞) = Area under the plasma concentration- time profile from time zero extrapolated to infinite time. It was calculated as AUC last + (C last\*/k el), where C last\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Milled and Unmilled PF-05251749: Cohort 4
|
13440 ng*hr/mL
Geometric Coefficient of Variation 27
|
19590 ng*hr/mL
Geometric Coefficient of Variation 19
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dosePopulation: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. This outcome measure was not planned to be analyzed for Cohort 1, 2 and 3, as pre-specified in protocol.
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Milled and Unmilled PF-05251749: Cohort 4
|
1007 ng/mL
Geometric Coefficient of Variation 18
|
3385 ng/mL
Geometric Coefficient of Variation 11
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dosePopulation: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. This outcome measure was not planned to be analyzed for Cohort 1, 2 and 3, as pre-specified in protocol.
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Milled and Unmilled PF-05251749: Cohort 4
|
2.50 hour
Interval 1.0 to 6.0
|
1.00 hour
Interval 0.5 to 1.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 1.5, 2.5, 4, and 8 hours post dosePopulation: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. This outcome measure was not planned to be analyzed for Cohort 1, 2 and 4, as pre-specified in protocol.
Area under the CSF concentration-time profile from time zero to the time of last quantifiable concentration (Clast).
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Cerebrospinal Fluid (CSF) Concentration (AUClast) of PF-05251749
|
1824 ng*hr/mL
Geometric Coefficient of Variation 31
|
10920 ng*hr/mL
Geometric Coefficient of Variation 28
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 1.5, 2.5, 4, and 8 hours post dosePopulation: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. This outcome measure was not planned to be analyzed for Cohort 1, 2 and 4, as pre-specified in protocol.
AUC (0 -∞) = Area under the CSF concentration- time profile from time zero extrapolated to infinite time. It was calculated as AUC last + (C last\*/k el), where C last\* was the predicted CSF concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Area Under the Curve From Time Zero to Extrapolated Cerebrospinal Fluid (CSF) Infinite Time [AUC (0 - ∞)] of PF-05251749
|
NA ng*hr/mL
Geometric Coefficient of Variation NA
Limited number of samples did not allow calculation of AUCinf; not analyzed.
|
NA ng*hr/mL
Geometric Coefficient of Variation NA
Limited number of samples did not allow calculation of AUCinf; not analyzed.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 1.5, 2.5, 4, and 8 hours post dosePopulation: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. This outcome measure was not planned to be analyzed for Cohort 1, 2 and 4, as pre-specified in protocol.
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Cmax) of PF-05251749
|
354.6 ng/mL
Geometric Coefficient of Variation 31
|
2331 ng/mL
Geometric Coefficient of Variation 29
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 1.5, 2.5, 4, and 8 hours post dosePopulation: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. This outcome measure was not planned to be analyzed for Cohort 1, 2 and 4, as pre-specified in protocol.
Outcome measures
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 Participants
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Time to Reach Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Tmax) of PF-05251749
|
1.59 hour
Interval 1.52 to 2.8
|
1.37 hour
Interval 1.37 to 4.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Cohort 1: PF-05251749 3 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Cohort 1: PF-05251749 30 mg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Cohort 1: PF-05251749 250 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Cohort 1: PF-05251749 500 mg (FED)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Cohort 2: PF-05251749 10 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Cohort 2: PF-05251749 100 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Cohort 2: PF-05251749 500 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Cohort 2: PF-05251749 1000 mg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Cohort 1-2: Placebo
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Cohort 3: PF-05251749 500 mg CSF
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Cohort 4: PF-05251749 500 mg Unmilled
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Cohort 4: PF-05251749 500 mg Milled
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cohort 1: PF-05251749 3 mg
n=6 participants at risk
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 30 mg
n=6 participants at risk
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 250 mg
n=6 participants at risk
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 1: PF-05251749 500 mg (FED)
n=6 participants at risk
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
|
Cohort 2: PF-05251749 10 mg
n=6 participants at risk
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 100 mg
n=6 participants at risk
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 500 mg
n=6 participants at risk
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 2: PF-05251749 1000 mg
n=6 participants at risk
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
|
Cohort 1-2: Placebo
n=15 participants at risk
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
|
Cohort 3: PF-05251749 500 mg CSF
n=6 participants at risk
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
|
Cohort 4: PF-05251749 500 mg Unmilled
n=6 participants at risk
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
|
Cohort 4: PF-05251749 500 mg Milled
n=6 participants at risk
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Cardiac disorders
Sinus node dysfunction
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
6.7%
1/15
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Cardiac disorders
Ventricular extrasystoles
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
6.7%
1/15
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
33.3%
2/6
|
0.00%
0/6
|
6.7%
1/15
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/15
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
16.7%
1/6
|
0.00%
0/15
|
33.3%
2/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/15
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
|
General disorders
Catheter site pain
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/15
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
|
General disorders
Feeling hot
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/15
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
|
General disorders
Hunger
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/15
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
|
General disorders
Vessel puncture site bruise
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/15
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
|
General disorders
Vessel puncture site pain
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
6.7%
1/15
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/15
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/15
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
|
Injury, poisoning and procedural complications
Post lumbar puncture syndrome
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/15
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Procedural headache
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/15
|
50.0%
3/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/15
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Investigations
Blood pressure diastolic decreased
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/15
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Investigations
Electrocardiogram QT prolonged
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/15
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/15
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/15
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/15
|
50.0%
3/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Nervous system disorders
Dizziness
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/15
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Nervous system disorders
Headache
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/15
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/15
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
6.7%
1/15
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Cold sweat
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/15
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER