Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Two Doses of PF-03654746 in Adults With Attention Deficit Hyperactivity Disorder (ADHD). (NCT NCT00531752)

Last Updated: 2016-02-19

Results Overview

AISRS: an 18-item scale administered by the investigator. It included 9 items that evaluated symptoms of inattention and 9 items that evaluated symptoms of impulsivity and hyperactivity. Each item was rated from 0 (none) to 3 (severe). AISRS total score was calculated as sum of all the items on the scale and ranged from 0 to 54. A higher score corresponded to a worse severity of ADHD.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

66 participants

Primary outcome timeframe

Baseline, Week 3

Results posted on

2016-02-19

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo First, Then PF-03654746 (Low Dose) Placebo matched to PF-03654746 capsule orally once daily for 3 weeks in first double-blind (DB) intervention period and then low dose of PF-03654746 capsule 1 milligram (mg) orally once daily for 3 weeks in second DB intervention period. A washout period of at least 7 days was maintained between each treatment period.	PF-03654746 (Low Dose) First, Then Placebo Low dose of PF-03654746 capsule 1 mg orally once daily for 3 weeks in first DB intervention period and then placebo matched to PF-03654746 capsule orally once daily for 3 weeks in second DB intervention period. A washout period of at least 7 days was maintained between each treatment period.	Placebo First, Then PF-03654746 (Flexible Dose) Placebo matched to PF-03654746 capsule orally once daily in the first DB intervention period and then PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in the second DB intervention period. A washout period of at least 7 days was maintained between each treatment period.	PF-03654746 (Flexible Dose) First, Then Placebo PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in the first DB intervention period and then placebo matched to PF-03654746 capsule orally once daily in the second DB intervention period. A washout period of at least 7 days was maintained between each treatment period.
First Double-blind Intervention Period STARTED	17	17	16	16
First Double-blind Intervention Period Treated	16	17	16	16
First Double-blind Intervention Period COMPLETED	11	13	9	13
First Double-blind Intervention Period NOT COMPLETED	6	4	7	3
Wash-out Period (at Least 7 Days) STARTED	11	13	9	13
Wash-out Period (at Least 7 Days) COMPLETED	11	13	9	13
Wash-out Period (at Least 7 Days) NOT COMPLETED	0	0	0	0
Second Double-blind Intervention Period STARTED	11	13	9	13
Second Double-blind Intervention Period COMPLETED	9	11	9	11
Second Double-blind Intervention Period NOT COMPLETED	2	2	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo First, Then PF-03654746 (Low Dose) Placebo matched to PF-03654746 capsule orally once daily for 3 weeks in first double-blind (DB) intervention period and then low dose of PF-03654746 capsule 1 milligram (mg) orally once daily for 3 weeks in second DB intervention period. A washout period of at least 7 days was maintained between each treatment period.	PF-03654746 (Low Dose) First, Then Placebo Low dose of PF-03654746 capsule 1 mg orally once daily for 3 weeks in first DB intervention period and then placebo matched to PF-03654746 capsule orally once daily for 3 weeks in second DB intervention period. A washout period of at least 7 days was maintained between each treatment period.	Placebo First, Then PF-03654746 (Flexible Dose) Placebo matched to PF-03654746 capsule orally once daily in the first DB intervention period and then PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in the second DB intervention period. A washout period of at least 7 days was maintained between each treatment period.	PF-03654746 (Flexible Dose) First, Then Placebo PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in the first DB intervention period and then placebo matched to PF-03654746 capsule orally once daily in the second DB intervention period. A washout period of at least 7 days was maintained between each treatment period.
First Double-blind Intervention Period Adverse Event	2	0	1	1
First Double-blind Intervention Period Other	1	4	4	0
First Double-blind Intervention Period Withdrawal by Subject	2	0	1	1
First Double-blind Intervention Period Lost to Follow-up	0	0	1	1
First Double-blind Intervention Period Randomized but not treated	1	0	0	0
Second Double-blind Intervention Period Adverse Event	1	1	0	0
Second Double-blind Intervention Period Other	1	1	0	0
Second Double-blind Intervention Period Withdrawal by Subject	0	0	0	1
Second Double-blind Intervention Period Lost to Follow-up	0	0	0	1

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Two Doses of PF-03654746 in Adults With Attention Deficit Hyperactivity Disorder (ADHD).

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo First, Then PF-03654746 (Low Dose) n=16 Participants Placebo matched to PF-03654746 capsule orally once daily for 3 weeks in first double-blind (DB) intervention period and then low dose of PF-03654746 capsule 1 milligram (mg) orally once daily for 3 weeks in second DB intervention period. A washout period of at least 7 days was maintained between each treatment period.	PF-03654746 (Low Dose) First, Then Placebo n=17 Participants Low dose of PF-03654746 capsule 1 mg orally once daily for 3 weeks in first DB intervention period and then placebo matched to PF-03654746 capsule orally once daily for 3 weeks in second DB intervention period. A washout period of at least 7 days was maintained between each treatment period.	Placebo First, Then PF-03654746 (Flexible Dose) n=16 Participants Placebo matched to PF-03654746 capsule orally once daily in the first DB intervention period and then PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in the second DB intervention period. A washout period of at least 7 days was maintained between each treatment period.	PF-03654746 (Flexible Dose) First, Then Placebo n=16 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in the first DB intervention period and then placebo matched to PF-03654746 capsule orally once daily in the second DB intervention period. A washout period of at least 7 days was maintained between each treatment period.	Total n=65 Participants Total of all reporting groups
Age, Continuous	37.3 years STANDARD_DEVIATION 12.6 • n=93 Participants	38.4 years STANDARD_DEVIATION 10.6 • n=4 Participants	37.9 years STANDARD_DEVIATION 10.2 • n=27 Participants	35.9 years STANDARD_DEVIATION 9.6 • n=483 Participants	37.4 years STANDARD_DEVIATION 10.6 • n=36 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Sex: Female, Male Male	16 Participants n=93 Participants	17 Participants n=4 Participants	16 Participants n=27 Participants	16 Participants n=483 Participants	65 Participants n=36 Participants

PRIMARY outcome

Timeframe: Baseline, Week 3

Population: Per Protocol (PP) set: all participants included in full analysis set (FAS=who received at least\[\>=\]1 dose of randomized study drug,had baseline and \>=1 post-baseline measurement of primary efficacy variable)and had no major protocol violation affecting primary efficacy variable. n=participants evaluable at specified time points for each arm.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=27 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=22 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=52 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Change From Baseline in Adult Attention Deficit Hyperactivity Disorder (ADHD) Investigator Symptom Rating Scale (AISRS) Total Score at Week 3 Baseline (n=27, 22, 52)	36.778 units on a scale Standard Deviation 8.5545	38.273 units on a scale Standard Deviation 4.8715	36.135 units on a scale Standard Deviation 7.3592
Change From Baseline in Adult Attention Deficit Hyperactivity Disorder (ADHD) Investigator Symptom Rating Scale (AISRS) Total Score at Week 3 Change at Week 3 (n=25, 21, 48)	-7.196 units on a scale Standard Deviation 8.7318	-5.745 units on a scale Standard Deviation 9.9824	-6.789 units on a scale Standard Deviation 8.5734

SECONDARY outcome

Timeframe: Baseline, Week 1, 2

Population: PP analysis set:all participants included in FAS and had no major protocol violation affecting primary efficacy variable. Here 'N' (number of participants analyzed) signifies participants who were evaluable for this measure and 'n' signifies those participants who were evaluable for this measure at specified time points for each arm, respectively.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=26 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=22 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=50 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Change From Baseline in Adult Attention Deficit Hyperactivity Disorder (ADHD) Investigator Symptom Rating Scale (AISRS) Total Score at Week 1 and 2 Week 1 (n=26, 22, 50)	-4.942 units on a scale Standard Deviation 6.2005	-3.591 units on a scale Standard Deviation 8.3476	-5.524 units on a scale Standard Deviation 7.4545
Change From Baseline in Adult Attention Deficit Hyperactivity Disorder (ADHD) Investigator Symptom Rating Scale (AISRS) Total Score at Week 1 and 2 Week 2 (n=23, 20, 46)	-6.022 units on a scale Standard Deviation 7.1486	-5.7 units on a scale Standard Deviation 7.8143	-7.109 units on a scale Standard Deviation 6.6139

SECONDARY outcome

Timeframe: Week 1, 2, 3

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=26 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=22 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=50 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Percentage of Participants With at Least 30 Percent Decrease From Baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) Total Score Week 1 (n=26, 22, 50)	15.385 percentage of participants	13.636 percentage of participants	24 percentage of participants
Percentage of Participants With at Least 30 Percent Decrease From Baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) Total Score Week 2 (n=23, 20, 46)	26.087 percentage of participants	30 percentage of participants	30.435 percentage of participants
Percentage of Participants With at Least 30 Percent Decrease From Baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) Total Score Week 3 (n=25, 21, 48)	24 percentage of participants	23.81 percentage of participants	29.167 percentage of participants

SECONDARY outcome

Timeframe: Week 1, 2, 3

CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected. Participants with a score of 1 (normal - not ill at all) or 2 (borderline mentally ill) are reported.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=26 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=22 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=50 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Percentage of Participants With 1 or 2 Score on Clinical Global Impression-Severity Scale (CGI-S) Week 3 (n=25, 21, 50)	8 percentage of participants	4.762 percentage of participants	6 percentage of participants
Percentage of Participants With 1 or 2 Score on Clinical Global Impression-Severity Scale (CGI-S) Week 1 (n=26, 22, 50)	3.846 percentage of participants	4.545 percentage of participants	2 percentage of participants
Percentage of Participants With 1 or 2 Score on Clinical Global Impression-Severity Scale (CGI-S) Week 2 (n=23, 20, 49)	0.0 percentage of participants	5 percentage of participants	4.082 percentage of participants

SECONDARY outcome

Timeframe: Week 1, 2, 3

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=26 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=22 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=50 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Percentage of Participants With Less Than or Equal to 18 Score on Adult ADHD Investigator Symptom Rating Scale (AISRS) Week 1 (n=26, 22, 50)	11.538 percentage of participants	4.545 percentage of participants	14 percentage of participants
Percentage of Participants With Less Than or Equal to 18 Score on Adult ADHD Investigator Symptom Rating Scale (AISRS) Week 2 (n=23, 20, 46)	21.739 percentage of participants	10 percentage of participants	13.043 percentage of participants
Percentage of Participants With Less Than or Equal to 18 Score on Adult ADHD Investigator Symptom Rating Scale (AISRS) Week 3 (n=25, 21, 48)	16 percentage of participants	14.286 percentage of participants	16.667 percentage of participants

SECONDARY outcome

Timeframe: Day 7, 14, 21

Population: PP analysis set: all participants included in FAS and had no major protocol violation affecting primary efficacy variable. Here 'N' (number of participants analyzed) signifies participants who were evaluable for this measure and 'n' signifies those participants who were evaluable for this measure at specified time points for each arm, respectively.

TASS: a time sensitive 18-item questionnaire completed by the participant that measured the severity of current ADHD symptoms. It included 9 items that evaluate symptoms of inattention sub-scale and 9 items that evaluate symptoms of impulsivity and hyperactivity sub-scale. Each item was rated from 0 (none) to 3 (severe). TASS total score was calculated as sum of all the items on the scale and ranged from 0 to 54. A higher total score corresponds to a worse severity of ADHD. TASS was administered each day from Day 1 to 14 and on Day 21 in each intervention period. Participants with sustained response were those who had at least 30 percent decrease from baseline in TASS total score, which was maintained at all visits up to the time of assessment. Sustained responders at Day 7, 14 and 21 were analyzed.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=21 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=18 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=45 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Percentage of Participants With Sustained Response of at Least 30 Percent Decrease From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score Day 7 (n=21, 18, 45)	38.095 percentage of participants	27.778 percentage of participants	33.333 percentage of participants
Percentage of Participants With Sustained Response of at Least 30 Percent Decrease From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score Day 21 (n=9, 6, 22)	33.333 percentage of participants	16.667 percentage of participants	40.909 percentage of participants
Percentage of Participants With Sustained Response of at Least 30 Percent Decrease From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score Day 14 (n=17, 16, 35)	23.529 percentage of participants	31.25 percentage of participants	31.429 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 1, 2, 3

AISRS: an 18-item scale administered by the investigator. It included 9 items that evaluated symptoms of inattention and 9 items that evaluated symptoms of impulsivity and hyperactivity. Each item was rated from 0 (none) to 3 (severe). The AISRS inattention and hyperactive/impulsive total subscale score range from 0 to 27. A higher total subscale score corresponded to a worse severity of ADHD inattention or hyperactivity/impulsivity.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=26 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=22 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=50 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Change From Baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) Subscale Scores at Week 1, 2 and 3 Week 1: Inattention (n=26, 22, 50)	-3.423 units on a scale Standard Deviation 3.6241	-1.636 units on a scale Standard Deviation 4.7338	-3.36 units on a scale Standard Deviation 4.3986
Change From Baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) Subscale Scores at Week 1, 2 and 3 Week 2: Inattention (n=23, 20, 46)	-4.326 units on a scale Standard Deviation 5.2627	-2.65 units on a scale Standard Deviation 4.5541	-4.022 units on a scale Standard Deviation 4.2985
Change From Baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) Subscale Scores at Week 1, 2 and 3 Week 1: Hyperactivity/Impulsivity (n=26, 22, 50)	-1.519 units on a scale Standard Deviation 3.708	-1.955 units on a scale Standard Deviation 4.0027	-2.164 units on a scale Standard Deviation 3.7001
Change From Baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) Subscale Scores at Week 1, 2 and 3 Week 2: Hyperactivity/Impulsivity (n=23, 20, 46)	-1.696 units on a scale Standard Deviation 3.1935	-3.05 units on a scale Standard Deviation 3.9766	-3.087 units on a scale Standard Deviation 3.2614
Change From Baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) Subscale Scores at Week 1, 2 and 3 Week 3: Hyperactivity/Impulsivity (n=25, 21, 48)	-3.111 units on a scale Standard Deviation 4.1894	-2.435 units on a scale Standard Deviation 4.8666	-3.07 units on a scale Standard Deviation 4.2411
Change From Baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) Subscale Scores at Week 1, 2 and 3 Week 3: Inattention (n=25, 21, 48)	-4.085 units on a scale Standard Deviation 5.7909	-3.31 units on a scale Standard Deviation 5.8019	-3.719 units on a scale Standard Deviation 5.195

SECONDARY outcome

Timeframe: Baseline, Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 21

Population: Analysis population included all participants in PP analysis set and 1 additional participant in PF-03654746 (Flexible Dose) for whom the post-baseline data was available.'N' (number of participants analyzed)=evaluable participants for this measure and 'n'= evaluable participants for this measure at specified time points for each arm, respectively.

TASS: a time sensitive 18-item questionnaire completed by the participant that measured the severity of current ADHD symptoms. It included 9 items that evaluate symptoms of inattention sub-scale and 9 items that evaluate symptoms of impulsivity and hyperactivity sub-scale. Each item was rated from 0 (none) to 3 (severe). TASS total score was calculated as sum of all the items on the scale and ranged from 0 to 54. A higher total score corresponded to a worse severity of ADHD. TASS was administered each day from Day 1 to 14 and on Day 21 in each intervention period.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=27 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=23 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=50 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Change From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score on Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 21 Day 1 (n=25, 22, 50)	-0.46 units on a scale Standard Deviation 5.3384	2.205 units on a scale Standard Deviation 14.9217	-4.75 units on a scale Standard Deviation 6.7221
Change From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score on Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 21 Day 2 (n=25, 21, 49)	-1.78 units on a scale Standard Deviation 6.8679	-0.952 units on a scale Standard Deviation 13.4433	-6.031 units on a scale Standard Deviation 10.2938
Change From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score on Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 21 Day 5 (n=26, 23, 49)	-4.942 units on a scale Standard Deviation 7.7153	-1.87 units on a scale Standard Deviation 10.2239	-6.622 units on a scale Standard Deviation 8.9353
Change From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score on Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 21 Day 7 (n=21, 18, 45)	-6.381 units on a scale Standard Deviation 7.7619	-6.222 units on a scale Standard Deviation 11.2736	-4.789 units on a scale Standard Deviation 9.7044
Change From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score on Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 21 Day 9 (n=21, 18, 45)	-4.238 units on a scale Standard Deviation 6.1352	-5.889 units on a scale Standard Deviation 9.9979	-5.889 units on a scale Standard Deviation 10.8664
Change From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score on Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 21 Day 12 (n=20, 18, 44)	-6.45 units on a scale Standard Deviation 7.3947	-6.167 units on a scale Standard Deviation 10.3099	-6.295 units on a scale Standard Deviation 10.3622
Change From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score on Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 21 Day 21 (n=9, 6, 22)	-9.889 units on a scale Standard Deviation 7.474	-4.583 units on a scale Standard Deviation 8.4346	-8.295 units on a scale Standard Deviation 8.299
Change From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score on Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 21 Day 3 (n=26, 21, 49)	-2.798 units on a scale Standard Deviation 12.1305	-3.857 units on a scale Standard Deviation 10.0476	-3.51 units on a scale Standard Deviation 10.3282
Change From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score on Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 21 Day 4 (n=26, 22, 46)	-4.981 units on a scale Standard Deviation 8.8346	-1.068 units on a scale Standard Deviation 14.4018	-3.761 units on a scale Standard Deviation 9.682
Change From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score on Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 21 Day 6 (n=27, 22, 44)	-5.833 units on a scale Standard Deviation 7.3183	-3.205 units on a scale Standard Deviation 10.5984	-6.841 units on a scale Standard Deviation 9.9573
Change From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score on Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 21 Day 8 (n=21, 19, 46)	-5.952 units on a scale Standard Deviation 7.0709	-6.526 units on a scale Standard Deviation 9.7389	-5.272 units on a scale Standard Deviation 9.804
Change From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score on Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 21 Day 10 (n=20, 20, 46)	-5.75 units on a scale Standard Deviation 6.9689	-7.525 units on a scale Standard Deviation 9.6579	-6.837 units on a scale Standard Deviation 10.7755
Change From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score on Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 21 Day 11 (n=21, 20, 46)	-5.619 units on a scale Standard Deviation 6.7341	-5.875 units on a scale Standard Deviation 11.2377	-6.924 units on a scale Standard Deviation 10.4371
Change From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score on Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 21 Day 13 (n=22, 19, 43)	-6.091 units on a scale Standard Deviation 6.4284	-5.658 units on a scale Standard Deviation 11.024	-7.488 units on a scale Standard Deviation 7.9279
Change From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score on Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 21 Day 14 (n=17, 16, 35)	-5.147 units on a scale Standard Deviation 6.7818	-7.5 units on a scale Standard Deviation 11.0559	-2.506 units on a scale Standard Deviation 25.19

SECONDARY outcome

Timeframe: Baseline, Week 3

Population: PP analysis set: all participants included in FAS and had no major protocol violation affecting primary efficacy variable. Here 'n' signifies those participants who were evaluable for this measure at specified time points for each arm, respectively.

The MADRS scale measures the depression level of a participant. It is administered as a semi-structured clinician interview. The total score is derived by adding the scores of the following 10 items: (1) Apparent sadness; (2) Reported sadness; (3) Inner tension; (4) Reduced sleep; (5) Reduced appetite; (6) Concentration difficulties; (7) Lassitude; (8) Inability to feel; (9) Pessimistic thoughts; (10) Suicidal thoughts. Each item is scored using a 6-point scale which ranges from 0 to 6 (a higher score indicates increased severity). The total score range was 0 to 60 where 0 indicates no depression and 60 indicates severely depressed.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=27 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=22 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=52 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Week 3 Baseline (n=27, 22, 52)	6.63 units on a scale Standard Deviation 3.9918	7.773 units on a scale Standard Deviation 5.0231	6.962 units on a scale Standard Deviation 4.5631
Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Week 3 Change at Week 3 (n=21, 19, 42)	-2.19 units on a scale Standard Deviation 3.9353	-1.289 units on a scale Standard Deviation 3.728	-0.524 units on a scale Standard Deviation 5.1572

SECONDARY outcome

Timeframe: Baseline, Week 3

HAM-A is a clinician-rated 14 item scale that provides an overall measure of global anxiety, including psychic (mental agitation and psychological distress) and somatic (physical complaints related to anxiety) symptoms. Each item was scored on a scale ranging from 0 (not present) to 4 (very severe) with a total score range of 0 to 56, where higher score indicates greater anxiety.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=27 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=22 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=52 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Week 3 Change at Week 3 (n=18, 21, 39)	-0.944 units on a scale Standard Deviation 2.514	-0.19 units on a scale Standard Deviation 2.5518	-0.487 units on a scale Standard Deviation 2.7732
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Week 3 Baseline (n=27, 22, 52)	5.333 units on a scale Standard Deviation 3.9223	6.045 units on a scale Standard Deviation 3.848	5.327 units on a scale Standard Deviation 3.3238

SECONDARY outcome

Timeframe: Baseline, Week 3

AIM-A: 66 item questionnaire completed by the participant to assess the impact of ADHD on the participant's quality of life. It is comprised of 4 global quality of life (QoL) items (current quality of life item \[CQoLI\], range:1 to 10; global limitation item \[GLI\]: range:1 to 4, on the right track item \[RTI\], range:1 to 3, more good days \[GD\] than bad days \[BD\], range:1 to 5, higher scores indicate a better QoL for all the 4 QoL items) and 6 multi-item subscales (living with ADHD, general well-being, performance and daily functioning \[PDF\], relationships and communication \[R/C\], Impact of symptoms-bother/concern \[IS-B/C\] scale, and impact of symptoms-interference \[IS-I\] scale). Participants responded to each item of multi-item subscale using a likert scale ranging from 1 (strongly agree) to 5 (strongly disagree). Multi-item subscale scores were calculated as an average of scores for the contributing items and transformed into 0 to 100 score where higher scores indicate a better QoL.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=27 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=22 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=52 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 Baseline: CQoLI (n=27, 22, 52)	6.481 units on a scale Standard Deviation 1.2746	6.409 units on a scale Standard Deviation 1.1406	6.423 units on a scale Standard Deviation 1.1219
Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 Baseline: RTI (n=27, 22, 52)	1.944 units on a scale Standard Deviation 0.5938	2.068 units on a scale Standard Deviation 0.3872	1.99 units on a scale Standard Deviation 0.4999
Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 Baseline: More GD than BD (n=27, 22, 52)	2.259 units on a scale Standard Deviation 0.7642	2.682 units on a scale Standard Deviation 0.8803	2.529 units on a scale Standard Deviation 0.8069
Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 Baseline: Living with ADHD (n=27, 22, 52)	53.935 units on a scale Standard Deviation 9.587	49.773 units on a scale Standard Deviation 12.4202	51.058 units on a scale Standard Deviation 10.5294
Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 Baseline: General well-being (n=27, 22, 52)	54.377 units on a scale Standard Deviation 11.1639	50.413 units on a scale Standard Deviation 17.2322	50.83 units on a scale Standard Deviation 13.2045
Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 Baseline: PDF (n=27, 22, 52)	37.176 units on a scale Standard Deviation 15.634	34.489 units on a scale Standard Deviation 15.3756	34.688 units on a scale Standard Deviation 13.5081
Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 Baseline: IS-B/C (n=27, 22, 52)	44.753 units on a scale Standard Deviation 16.8364	42.235 units on a scale Standard Deviation 19.7475	42.201 units on a scale Standard Deviation 16.7033
Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 Baseline: IS-I (n=27, 22, 52)	47.994 units on a scale Standard Deviation 10.1284	46.78 units on a scale Standard Deviation 9.1366	46.768 units on a scale Standard Deviation 8.8729
Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 Change at Week 3: CQoLI (n=25, 21, 47)	0.04 units on a scale Standard Deviation 0.9456	0.286 units on a scale Standard Deviation 1.2306	0.17 units on a scale Standard Deviation 1.3116
Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 Change at Week 3: GLI (n=25, 21, 47)	0.2 units on a scale Standard Deviation 0.4564	0.214 units on a scale Standard Deviation 0.7676	0.106 units on a scale Standard Deviation 0.6421
Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 Change at Week 3: More GD than BD (n=25, 21, 47)	-0.32 units on a scale Standard Deviation 0.6272	-0.238 units on a scale Standard Deviation 0.9826	-0.106 units on a scale Standard Deviation 0.9997
Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 Change at Week 3: Living with ADHD (n=25, 21, 47)	2.55 units on a scale Standard Deviation 4.5712	1.905 units on a scale Standard Deviation 5.5145	3.005 units on a scale Standard Deviation 7.2121
Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 Change at Week 3:General well-being (n=25, 21, 47)	4.909 units on a scale Standard Deviation 7.1999	1.299 units on a scale Standard Deviation 8.9642	4.884 units on a scale Standard Deviation 10.3145
Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 Change at Week 3: PDF (n=25, 21, 47)	12.65 units on a scale Standard Deviation 14.0698	11.488 units on a scale Standard Deviation 21.7501	10.718 units on a scale Standard Deviation 18.3226
Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 Change at Week 3: IS-B/C (n=25, 21, 47)	3 units on a scale Standard Deviation 12.9465	0.463 units on a scale Standard Deviation 18.6097	7.417 units on a scale Standard Deviation 13.7471
Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 Baseline: R/C (n=27, 22, 52)	65.856 units on a scale Standard Deviation 16.2652	57.955 units on a scale Standard Deviation 15.7281	61.358 units on a scale Standard Deviation 14.7036
Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 Change at Week 3: RTI (n=25, 21, 47)	-0.02 units on a scale Standard Deviation 0.5492	-0.071 units on a scale Standard Deviation 0.6381	-0.074 units on a scale Standard Deviation 0.5612
Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 Change at Week 3: R/C (n=25, 21, 47)	5.125 units on a scale Standard Deviation 13.0457	0.298 units on a scale Standard Deviation 16.3773	3.358 units on a scale Standard Deviation 13.4687
Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 Change at Week 3: IS-I (n=25, 21, 47)	2.389 units on a scale Standard Deviation 8.2023	0.463 units on a scale Standard Deviation 9.3204	2.896 units on a scale Standard Deviation 10.6124
Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 Baseline: GLI (n=27, 22, 52)	1.815 units on a scale Standard Deviation 0.7091	1.705 units on a scale Standard Deviation 0.7505	1.663 units on a scale Standard Deviation 0.624

SECONDARY outcome

Timeframe: Baseline, Week 3

AAQoL is a 29-item questionnaire consisting of 4 subscales: life productivity (11 items), psychological health (\[PH\] 6 items), life outlook (7 items) and relationships (5 items). Participants rated each item on a scale ranging from 1 (not at all/never) to 5 (extremely/very often). The scores of each item were then transformed to a 0 to 100 point scale, higher scores indicating better quality of life. The score for each subscale was calculated as the sum of the corresponding item scores. Total score ranges were: life productivity (0 to 1100), psychological health (0 to 600), life outlook (0 to 700) and relationships (0 to 500), where higher subscale score indicates better quality of life for each subscale.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=27 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=22 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=52 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Change From Baseline in Adult ADHD Quality of Life Scale (AAQOL) Subscale Score at Week 3 Baseline: Psychological health (n=27, 22, 52)	163.889 units on a scale Standard Deviation 42.9296	146.591 units on a scale Standard Deviation 66.0517	167.788 units on a scale Standard Deviation 59.4782
Change From Baseline in Adult ADHD Quality of Life Scale (AAQOL) Subscale Score at Week 3 Baseline: Relationships (n=27, 22, 52)	152.778 units on a scale Standard Deviation 49.1922	154.545 units on a scale Standard Deviation 46.0566	163.942 units on a scale Standard Deviation 49.856
Change From Baseline in Adult ADHD Quality of Life Scale (AAQOL) Subscale Score at Week 3 Change at Week 3: Life productivity (n=25, 21, 47)	3 units on a scale Standard Deviation 84.1068	8.333 units on a scale Standard Deviation 112.7312	22.606 units on a scale Standard Deviation 85.7606
Change From Baseline in Adult ADHD Quality of Life Scale (AAQOL) Subscale Score at Week 3 Change at Week 3: PH (n=25, 21, 47)	0 units on a scale Standard Deviation 50.5181	1.786 units on a scale Standard Deviation 57.1847	11.436 units on a scale Standard Deviation 63.9415
Change From Baseline in Adult ADHD Quality of Life Scale (AAQOL) Subscale Score at Week 3 Change at Week 3: Life outlook (n=25, 21, 47)	-13 units on a scale Standard Deviation 56.9951	14.286 units on a scale Standard Deviation 68.9526	-8.511 units on a scale Standard Deviation 42.6776
Change From Baseline in Adult ADHD Quality of Life Scale (AAQOL) Subscale Score at Week 3 Change at Week 3: Relationships (n=25, 21, 47)	-1.5 units on a scale Standard Deviation 31.9342	1.19 units on a scale Standard Deviation 46.2508	-3.723 units on a scale Standard Deviation 45.662
Change From Baseline in Adult ADHD Quality of Life Scale (AAQOL) Subscale Score at Week 3 Baseline: Life productivity (n=27, 22, 52)	306.481 units on a scale Standard Deviation 109.9809	292.045 units on a scale Standard Deviation 72.5334	281.25 units on a scale Standard Deviation 107.9982
Change From Baseline in Adult ADHD Quality of Life Scale (AAQOL) Subscale Score at Week 3 Baseline: Life outlook (n=27, 22, 52)	229.63 units on a scale Standard Deviation 65.7929	194.318 units on a scale Standard Deviation 69.8348	218.269 units on a scale Standard Deviation 59.0188

SECONDARY outcome

Timeframe: Baseline, Week 3

Population: PP analysis set: all participants included in FAS and had no major protocol violation affecting primary efficacy variable. Here 'n' signifies those participants who were evaluable for given subscale at specified time points for each arm, respectively.

SDS was a participant-rated questionnaire assessing the effect of the participant's symptoms on the 3 domains/subscales: work/school, social life/leisure activities, and family/home management. Each domain was rated on visual analog scale ranges from 0 to 10 where 0=not at all impaired and 10=extremely impaired, and total SDS score was calculated as a sum of all the domains with a score range of 0=not at all impaired to 30=extremely impaired. Disability scores were reported for each of the domains/subscales. Higher scores reflect greater impairment.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=27 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=22 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=52 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Change From Baseline in Sheehan Disability Scale (SDS) Subscale Scores at Week 3 Baseline: Work/school (n=26, 21, 50)	6.058 units on a scale Standard Deviation 2.2375	6.095 units on a scale Standard Deviation 2.0894	6.36 units on a scale Standard Deviation 1.977
Change From Baseline in Sheehan Disability Scale (SDS) Subscale Scores at Week 3 Baseline: Social life (n=27, 22, 52)	4.593 units on a scale Standard Deviation 2.0383	5.227 units on a scale Standard Deviation 2.5153	5.01 units on a scale Standard Deviation 2.0757
Change From Baseline in Sheehan Disability Scale (SDS) Subscale Scores at Week 3 Baseline: Family life/home (n=27, 22, 52)	5.019 units on a scale Standard Deviation 2.0357	5.705 units on a scale Standard Deviation 2.0393	5.673 units on a scale Standard Deviation 1.8335
Change From Baseline in Sheehan Disability Scale (SDS) Subscale Scores at Week 3 Change at Week 3: Work/school (n=24, 18, 45)	-0.813 units on a scale Standard Deviation 1.3089	-0.222 units on a scale Standard Deviation 2.2572	-0.411 units on a scale Standard Deviation 1.7526
Change From Baseline in Sheehan Disability Scale (SDS) Subscale Scores at Week 3 Change at Week 3: Social life (n=25, 21, 47)	-0.8 units on a scale Standard Deviation 1.75	-0.619 units on a scale Standard Deviation 2.4592	-0.436 units on a scale Standard Deviation 1.9043
Change From Baseline in Sheehan Disability Scale (SDS) Subscale Scores at Week 3 Change at Week 3: Family life/home (n=25, 21, 47)	-0.78 units on a scale Standard Deviation 1.5618	-0.071 units on a scale Standard Deviation 2.2709	-0.532 units on a scale Standard Deviation 1.6596

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 1, 2, 3

Participant-rated 12-item questionnaire to assess sleep quality and quantity. The items contribute to each scale and are averaged to create the 7 subscale scores: sleep disturbance, snoring, awaken short of breath (ASoB) or with a headache, somnolence, sleep adequacy, sleep quantity (range 0 to 24) and optimal sleep, and overall sleep problem index (SPI) I (range 0 to 600) and II. Except for sleep quantity and sleep problem index I, scores are transformed (actual raw score minus lowest possible score divided by possible raw score range\* 100); total score range: 0 to 100; higher score = greater intensity of attribute. Except for sleep quantity, higher scores=greater impairment. Scales with at least one item answered was used to generate a scale score.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=27 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=22 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=52 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Baseline: Snoring (n=26, 22, 51)	43.462 units on a scale Standard Deviation 29.1125	44.091 units on a scale Standard Deviation 32.9009	40.784 units on a scale Standard Deviation 29.9895
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Baseline: ASoB (n=27, 22, 52)	3.333 units on a scale Standard Deviation 8.7706	7.727 units on a scale Standard Deviation 17.7098	6.154 units on a scale Standard Deviation 14.1635
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Baseline: Sleep quantity (n=27, 22, 52)	6.537 units on a scale Standard Deviation 0.95	6.705 units on a scale Standard Deviation 0.9594	6.673 units on a scale Standard Deviation 1.0379
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Baseline: Sleep adequacy (n=26, 22, 51)	40.962 units on a scale Standard Deviation 22.8044	41.364 units on a scale Standard Deviation 26.1944	39.804 units on a scale Standard Deviation 23.4512
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Baseline: SPI I (n=26, 22, 51)	201.538 units on a scale Standard Deviation 69.0329	214.091 units on a scale Standard Deviation 109.1377	210.196 units on a scale Standard Deviation 87.7836
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Baseline: SPI II (n=27, 22, 52)	33.251 units on a scale Standard Deviation 12.8016	37.519 units on a scale Standard Deviation 18.3575	34.848 units on a scale Standard Deviation 15.5578
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 1: Sleep disturbance (n=26, 22, 50)	18.245 units on a scale Standard Deviation 30.9066	4.489 units on a scale Standard Deviation 23.7105	-8.263 units on a scale Standard Deviation 18.8354
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 1: Snoring (n=25, 21, 48)	-14.8 units on a scale Standard Deviation 19.1746	-4.286 units on a scale Standard Deviation 17.7684	-10.417 units on a scale Standard Deviation 14.1359
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 1: Sleep quantity (n=25, 22, 48)	-0.42 units on a scale Standard Deviation 1.3204	-0.114 units on a scale Standard Deviation 0.8442	0.198 units on a scale Standard Deviation 1.0249
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 1: Optimal sleep (n=26, 22, 50)	0 units on a scale Standard Deviation 0.4899	0 units on a scale Standard Deviation 0.5345	-0.14 units on a scale Standard Deviation 0.5349
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 1: SPI I (n=25, 22, 49)	35.2 units on a scale Standard Deviation 81.7068	25 units on a scale Standard Deviation 105.9088	-21.224 units on a scale Standard Deviation 85.9901
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 1: SPI II (n=26, 22, 50)	7.65 units on a scale Standard Deviation 16.0588	2.936 units on a scale Standard Deviation 17.1929	-3.875 units on a scale Standard Deviation 14.2472
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 2: Sleep disturbance (n=23, 20, 46)	3.904 units on a scale Standard Deviation 18.0117	0.438 units on a scale Standard Deviation 27.3712	-11.984 units on a scale Standard Deviation 15.9101
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 2: Snoring (n=22, 19, 45)	-12.273 units on a scale Standard Deviation 17.1636	-17.368 units on a scale Standard Deviation 14.4692	-12 units on a scale Standard Deviation 14.554
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 2: ASoB (n=23, 20, 46)	0.435 units on a scale Standard Deviation 11.0693	1.5 units on a scale Standard Deviation 14.2441	-3.478 units on a scale Standard Deviation 11.1987
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 2: SPI I (n=22, 20, 45)	-15.455 units on a scale Standard Deviation 71.6956	1.5 units on a scale Standard Deviation 103.937	-45.333 units on a scale Standard Deviation 74.8817
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 2: SPI II (n=23, 20, 46)	-0.242 units on a scale Standard Deviation 11.7718	-1.438 units on a scale Standard Deviation 17.3576	-8.155 units on a scale Standard Deviation 12.6707
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 3: Sleep disturbance (n=25, 21, 47)	-0.875 units on a scale Standard Deviation 18.0287	6.31 units on a scale Standard Deviation 24.7652	-12.114 units on a scale Standard Deviation 15.1541
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 3: ASoB (n=25, 21, 47)	-0.4 units on a scale Standard Deviation 12.0692	6.19 units on a scale Standard Deviation 19.3588	1.702 units on a scale Standard Deviation 22.4886
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 3: Sleep quantity (n=24, 20, 47)	-0.354 units on a scale Standard Deviation 0.8658	-0.025 units on a scale Standard Deviation 0.9244	0.16 units on a scale Standard Deviation 1.0638
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 3: Optimal sleep (n=25, 21, 50)	0.08 units on a scale Standard Deviation 0.4491	0 units on a scale Standard Deviation 0.5477	-0.12 units on a scale Standard Deviation 0.5206
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 3: Sleep Adequacy (n=24, 21, 45)	3.958 units on a scale Standard Deviation 19.1663	-2.381 units on a scale Standard Deviation 25.5254	3 units on a scale Standard Deviation 17.235
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 3: Somnolence (n=24, 21, 45)	-8.889 units on a scale Standard Deviation 19.5274	0.635 units on a scale Standard Deviation 13.3591	-1.704 units on a scale Standard Deviation 12.4848
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 3: SPI I (n=24, 21, 45)	-20.833 units on a scale Standard Deviation 71.7433	31.905 units on a scale Standard Deviation 108.3337	-25.778 units on a scale Standard Deviation 71.6205
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 3: SPI II (n=25, 21, 47)	-2.511 units on a scale Standard Deviation 14.1763	4.636 units on a scale Standard Deviation 18.1315	-6.238 units on a scale Standard Deviation 12.4191
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Baseline: Sleep disturbance (n=27, 22, 52)	27.894 units on a scale Standard Deviation 19.427	34.489 units on a scale Standard Deviation 20.6801	29.892 units on a scale Standard Deviation 20.4408
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Baseline: Optimal sleep (n=27, 22, 52)	1.593 units on a scale Standard Deviation 0.4169	1.5 units on a scale Standard Deviation 0.4082	1.558 units on a scale Standard Deviation 0.416
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Baseline: Somnolence (n=26, 22, 51)	31.795 units on a scale Standard Deviation 19.6238	32.727 units on a scale Standard Deviation 19.5893	30.85 units on a scale Standard Deviation 20.2522
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 1: ASoB (n=26, 22, 50)	4.231 units on a scale Standard Deviation 15.7919	-2.273 units on a scale Standard Deviation 9.2231	-1.6 units on a scale Standard Deviation 14.3371
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 1: Sleep Adequacy (n=25, 22, 49)	-1.8 units on a scale Standard Deviation 15.6045	-6.818 units on a scale Standard Deviation 27.1041	-0.408 units on a scale Standard Deviation 21.5985
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 1: Somnolence (n=25, 22, 49)	-8.267 units on a scale Standard Deviation 21.7545	-1.818 units on a scale Standard Deviation 13.8674	-1.769 units on a scale Standard Deviation 16.4444
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 2: Sleep quantity (22, 20, 46)	-0.182 units on a scale Standard Deviation 0.958	0.025 units on a scale Standard Deviation 0.8955	0.152 units on a scale Standard Deviation 0.9121
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 2: Optimal sleep (n=23, 20, 49)	0.065 units on a scale Standard Deviation 0.4074	-0.1 units on a scale Standard Deviation 0.4472	-0.122 units on a scale Standard Deviation 0.4845
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 2: Sleep Adequacy (n=22, 20, 45)	7.955 units on a scale Standard Deviation 17.6378	4.5 units on a scale Standard Deviation 23.6699	6.111 units on a scale Standard Deviation 24.0711
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 2: Somnolence (n=22, 20, 45)	-6.061 units on a scale Standard Deviation 16.9542	-4.333 units on a scale Standard Deviation 14.3515	-5.333 units on a scale Standard Deviation 14.6059
Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 Change at Week 3: Snoring (n=24, 20, 44)	-7.917 units on a scale Standard Deviation 14.44	-5.5 units on a scale Standard Deviation 20.1246	-6.364 units on a scale Standard Deviation 13.6554

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 1, 2, 3

SSQ is a 5-item self-report scale that was designed to evaluate the amount and quality of sleep and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), total awake after sleep onset (WASO \[1 item\]), quality of sleep (1 item). Latency subscale score ranges from 0-840 minutes. Lower value indicates better sleep.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=27 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=22 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=52 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Change From Baseline in Subjective Sleep Questionnaire (SSQ) Latency Subscale Scores at Week 1, 2 and 3 Baseline (n=27, 22, 52)	30.333 minutes Standard Deviation 35.7464	31.364 minutes Standard Deviation 29.7582	29.067 minutes Standard Deviation 31.8087
Change From Baseline in Subjective Sleep Questionnaire (SSQ) Latency Subscale Scores at Week 1, 2 and 3 Change at Week 2 (n=21, 19, 43)	-3.024 minutes Standard Deviation 23.4763	-12.632 minutes Standard Deviation 31.1858	-11.105 minutes Standard Deviation 23.2396
Change From Baseline in Subjective Sleep Questionnaire (SSQ) Latency Subscale Scores at Week 1, 2 and 3 Change at Week 3 (n=18, 11, 36)	-3.222 minutes Standard Deviation 36.2086	4.091 minutes Standard Deviation 66.954	-11.958 minutes Standard Deviation 30.2856
Change From Baseline in Subjective Sleep Questionnaire (SSQ) Latency Subscale Scores at Week 1, 2 and 3 Change at Week 1 (n=25, 22, 43)	24.6 minutes Standard Deviation 89.6858	-3.409 minutes Standard Deviation 46.2302	0.837 minutes Standard Deviation 60.9442

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 1, 2, 3

SSQ is a 5-item self-report scale that was designed to evaluate the amount and quality of sleep and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), WASO (1 item), quality of sleep (1 item). Hours of sleep subscale score ranges from 0-16 hours. Higher value indicates better sleep.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=27 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=22 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=52 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Change From Baseline in Subjective Sleep Questionnaire (SSQ) Hours of Sleep Subscale Scores at Week 1, 2 and 3 Baseline (n=27, 22, 52)	6.05 hours Standard Deviation 1.0963	6.48 hours Standard Deviation 1.2806	6.364 hours Standard Deviation 1.2534
Change From Baseline in Subjective Sleep Questionnaire (SSQ) Hours of Sleep Subscale Scores at Week 1, 2 and 3 Change at Week 1 (n=25, 22, 43)	0.147 hours Standard Deviation 1.4865	0.414 hours Standard Deviation 2.0816	0.763 hours Standard Deviation 1.5914
Change From Baseline in Subjective Sleep Questionnaire (SSQ) Hours of Sleep Subscale Scores at Week 1, 2 and 3 Change at Week 2 (21, 19, 43)	0.414 hours Standard Deviation 1.2911	0.319 hours Standard Deviation 1.7	0.865 hours Standard Deviation 1.4959
Change From Baseline in Subjective Sleep Questionnaire (SSQ) Hours of Sleep Subscale Scores at Week 1, 2 and 3 Change at Week 3 (n=18, 11, 36)	-0.148 hours Standard Deviation 1.7562	-0.17 hours Standard Deviation 2.0091	0.717 hours Standard Deviation 1.2305

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 1, 2, 3

SSQ is a 5-item self-report scale that was designed to evaluate the amount and quality of sleep and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), WASO (1 item), quality of sleep (1 item). Number of awakenings subscale score ranges from 0 to 30. Lower value indicates better sleep.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=27 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=22 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=52 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Change From Baseline in Subjective Sleep Questionnaire (SSQ) Number of Awakenings Subscale Scores at Week 1, 2 and 3 Baseline (n=27, 22, 52)	1.37 awakenings Standard Deviation 1.4317	1.182 awakenings Standard Deviation 1.0065	1.298 awakenings Standard Deviation 1.2258
Change From Baseline in Subjective Sleep Questionnaire (SSQ) Number of Awakenings Subscale Scores at Week 1, 2 and 3 Change at Week 1 (n=25, 22, 43)	0.12 awakenings Standard Deviation 1.6788	0.5 awakenings Standard Deviation 1.7252	-0.209 awakenings Standard Deviation 1.4402
Change From Baseline in Subjective Sleep Questionnaire (SSQ) Number of Awakenings Subscale Scores at Week 1, 2 and 3 Change at Week 2 (n=21, 19, 43)	-0.333 awakenings Standard Deviation 1.977	0.158 awakenings Standard Deviation 1.2589	-0.419 awakenings Standard Deviation 1.2293
Change From Baseline in Subjective Sleep Questionnaire (SSQ) Number of Awakenings Subscale Scores at Week 1, 2 and 3 Change at Week 3 (n=18, 11, 36)	0.028 awakenings Standard Deviation 2.0398	0.045 awakenings Standard Deviation 1.4222	-0.361 awakenings Standard Deviation 1.2627

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 1, 2, 3

SSQ is a 5-item self-report scale that was designed to evaluate the amount and quality of sleep and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), WASO (1 item), quality of sleep (1 item). Total WASO subscale score ranges from 0 to 24 hours. Lower value indicates better sleep.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=27 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=22 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=52 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Change From Baseline in Subjective Sleep Questionnaire (SSQ) Total Awake After Sleep Onset (WASO) Subscale Scores at Week 1, 2 and 3 Change at Week 2 (n=21, 19, 43)	-0.133 hours Standard Deviation 0.7064	-0.167 hours Standard Deviation 0.8035	-0.228 hours Standard Deviation 0.8409
Change From Baseline in Subjective Sleep Questionnaire (SSQ) Total Awake After Sleep Onset (WASO) Subscale Scores at Week 1, 2 and 3 Change at Week 3 (n=18, 11, 36)	0.091 hours Standard Deviation 0.6291	0.329 hours Standard Deviation 1.3329	-0.313 hours Standard Deviation 0.6863
Change From Baseline in Subjective Sleep Questionnaire (SSQ) Total Awake After Sleep Onset (WASO) Subscale Scores at Week 1, 2 and 3 Baseline (n=27, 22, 52)	0.432 hours Standard Deviation 0.6295	0.578 hours Standard Deviation 0.8214	0.529 hours Standard Deviation 0.7442
Change From Baseline in Subjective Sleep Questionnaire (SSQ) Total Awake After Sleep Onset (WASO) Subscale Scores at Week 1, 2 and 3 Change at Week 1 (25, 22, 43)	0.109 hours Standard Deviation 0.5542	0.013 hours Standard Deviation 1.2797	-0.286 hours Standard Deviation 0.7444

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 1, 2, 3

SSQ is a 5-item self-report scale that was designed to evaluate the amount and quality of sleep and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), WASO (1 item), quality of sleep (1 item). Quality of sleep subscale score ranges from 0-100. Higher score indicates better quality of sleep.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=27 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=22 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=52 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Change From Baseline in Subjective Sleep Questionnaire (SSQ) Quality of Sleep Subscale Scores at Week 1, 2 and 3 Baseline (n=27, 22, 52)	57.093 units on a scale Standard Deviation 19.7582	55 units on a scale Standard Deviation 23.4663	56.202 units on a scale Standard Deviation 20.9533
Change From Baseline in Subjective Sleep Questionnaire (SSQ) Quality of Sleep Subscale Scores at Week 1, 2 and 3 Change at Week 1 (n=25, 22, 42)	-4.06 units on a scale Standard Deviation 21.0616	0.5 units on a scale Standard Deviation 25.6715	8.393 units on a scale Standard Deviation 25.5447
Change From Baseline in Subjective Sleep Questionnaire (SSQ) Quality of Sleep Subscale Scores at Week 1, 2 and 3 Change at Week 2 (n=21, 19, 43)	8.286 units on a scale Standard Deviation 22.3375	11.105 units on a scale Standard Deviation 22.6124	9.43 units on a scale Standard Deviation 20.5434
Change From Baseline in Subjective Sleep Questionnaire (SSQ) Quality of Sleep Subscale Scores at Week 1, 2 and 3 Change at Week 3 (n=18, 11, 36)	7.222 units on a scale Standard Deviation 21.7764	0.182 units on a scale Standard Deviation 44.302	10.389 units on a scale Standard Deviation 22.8602

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 1 week after last study dose

Population: Safety analysis set consisted of all participants who took at least 1 dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Laboratory parameters included hematology (hemoglobin, hematocrit, red blood cell count, platelets, leukocytes, total neutrophils, eosinophils, basophils, lymphocytes, monocytes); liver function (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, albumin, total protein); renal function (creatinine, blood urea nitrogen, uric acid, sodium, potassium, chloride, bicarbonate, calcium); urinalysis (protein, blood), and clinical chemistry (glucose).

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=28 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=25 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=55 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Number of Participants With Clinically Significant Laboratory Test Abnormalities	5 participants	9 participants	10 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to End of Treatment (Week 3 of period 2)

Criteria for potential clinical concern in ECG parameters: maximum PR interval of greater than or equal to (\>=) 300 milliseconds (msec), maximum QRS interval \>=200 msec, maximum QTc interval of 450 to \<480 msec, 480 to \<500 msec and \>=500 msec.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=28 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=25 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=57 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Number of Participants With Electrocardiogram (ECG) Findings	1 participants	0 participants	1 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 1 week after last study dose

Criteria for potential clinical concern in vital signs: systolic blood pressure (BP) less than (\<) 90 millimeters of mercury (mmHg), diastolic BP \<50 mmHg, supine and sitting heart rate \<40 beats per minute (bpm) or \>120 bpm, standing and erect heart rate \<40 bpm or \>140 bpm. Maximum increase from baseline in systolic BP \>=30 mmHg, maximum increase from baseline in diastolic BP \>=20 mmHg.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=28 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=25 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=55 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Number of Participants With Clinically Significant Vital Sign Abnormalities	0 participants	0 participants	1 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 1 week after last study dose (1 week after end of Period 2)

Population: Safety analysis set consisted of all participants who took at least 1 dose of study medication.

Analysis include general physical examination and assessment of head, ears, eyes, ocular fundi, nose, mouth, throat, neck, thyroid, lungs, heart, breasts, abdomen and musculoskeletal system.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=28 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=25 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=58 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Number of Participants With Change From Baseline in Physical Examination and Neurological Examination	0 participants	0 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 up to Day 21

Population: Safety analysis set consisted of all participants who took at least 1 dose of study medication.

Treatment duration was defined as the total number of dosing days from first to last day of study drug administration in each period.

Outcome measures

Outcome measures
Measure	PF-03654746 (Low Dose) n=28 Participants PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	PF-03654746 (Flexible Dose) n=25 Participants PF-03654746 capsule 0.5 mg orally once daily in the first week, PF-03654746 capsule 1 mg orally once daily in the second week and PF-03654746 2 mg orally once daily in the third week, depending upon the investigator's discretion and tolerability, in first or second DB intervention period.	Placebo n=58 Participants Placebo matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Treatment Duration	21 days Interval 1.0 to 30.0	21 days Interval 7.0 to 27.0	21 days Interval 3.0 to 45.0

Adverse Events

PF-03654746 (Low Dose)

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

PF-03654746 (Flexible Dose)

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

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