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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00531752
• Collaborator: (none)
• Enrollment: 66
• Locations: 7
• Arms: 3
• Duration (Months): 9
• Patients Per Site: 9.4
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether PF-03654746 is effective in the treatment of Adult Attention Deficit Hyperactivity Disorder (ADHD). This will be a randomized, double-blind, crossover study in which adults with ADHD will receive 3 weeks of treatment with PF-03654746, either a low dose (1 mg), or flexible dose (0.50 mg titrated up to 2 mg), and 3 weeks of placebo. A washout period will separate the 2 treatment periods. Participants will be required to washout of prior ADHD medication before entering the study. Participants will be required to come to the site for 10 visits over approximately a 10-week period.

Condition or Disease	Intervention/Treatment	Phase
Attention Deficit Hyperactivity Disorder	Drug: PF-03654746; Drug: Placebo capsules; Drug: PF-03654746	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase Iia, Randomized, Double Blind, Placebo Controlled, Three-treatment, Two-period Crossover Study Of The Efficacy And Safety Of Two Doses Of Pf-03654746 In Adults With Attention Deficit Hyperactivity Disorder
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Flexible Dose	Drug: PF-03654746; Dosage Form: 0.5 mg capsules of PF-03654746 Dosage: 0.5 mg QD for Days 1-7, then 1.0 mg QD Days 8-14, then 2.0 mg QD Days 15-21
Placebo Comparator: Placebo	Drug: Placebo capsules; Dosage Form: matching placebo capsules Dosage: Subjects will take two placebo capsules each morning throughout the 3 week double-blind treatment placebo treatment period.
Experimental: Fixed Dose	Drug: PF-03654746; Dosage Form: 0.5 mg capsules of PF-03654746 Dosage: 1 mg (2 x 0.5 mg capsules) of PF-03654746 given daily for three weeks

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Adult Attention Deficit Hyperactivity Disorder (ADHD) Investigator Symptom Rating Scale (AISRS) Total Score at Week 3 [Baseline, Week 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). 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.

Secondary Outcome Measures

1. Change From Baseline in Adult Attention Deficit Hyperactivity Disorder (ADHD) Investigator Symptom Rating Scale (AISRS) Total Score at Week 1 and 2 [Baseline, Week 1, 2]

   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.

2. Percentage of Participants With at Least 30 Percent Decrease From Baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) Total Score [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). 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.

3. Percentage of Participants With 1 or 2 Score on Clinical Global Impression-Severity Scale (CGI-S) [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.

4. Percentage of Participants With Less Than or Equal to 18 Score on Adult ADHD Investigator Symptom Rating Scale (AISRS) [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). 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.

5. 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, 14, 21]

   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.

6. Change From Baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) Subscale Scores at Week 1, 2 and 3 [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.

7. 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 [Baseline, Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 21]

   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.

8. Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Week 3 [Baseline, Week 3]

   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.

9. Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Week 3 [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.

10. Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3 [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.

11. Change From Baseline in Adult ADHD Quality of Life Scale (AAQOL) Subscale Score at Week 3 [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.

12. Change From Baseline in Sheehan Disability Scale (SDS) Subscale Scores at Week 3 [Baseline, Week 3]

    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.

Other Outcome Measures

1. Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3 [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.

2. Change From Baseline in Subjective Sleep Questionnaire (SSQ) Latency Subscale Scores at Week 1, 2 and 3 [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.

3. Change From Baseline in Subjective Sleep Questionnaire (SSQ) Hours of Sleep Subscale Scores at Week 1, 2 and 3 [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.

4. Change From Baseline in Subjective Sleep Questionnaire (SSQ) Number of Awakenings Subscale Scores at Week 1, 2 and 3 [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.

5. Change From Baseline in Subjective Sleep Questionnaire (SSQ) Total Awake After Sleep Onset (WASO) Subscale Scores at Week 1, 2 and 3 [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.

6. Change From Baseline in Subjective Sleep Questionnaire (SSQ) Quality of Sleep Subscale Scores at Week 1, 2 and 3 [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.

7. Number of Participants With Clinically Significant Laboratory Test Abnormalities [Baseline up to 1 week after last study dose]

   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).

8. Number of Participants With Electrocardiogram (ECG) Findings [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.

9. Number of Participants With Clinically Significant Vital Sign Abnormalities [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.

10. Number of Participants With Change From Baseline in Physical Examination and Neurological Examination [Baseline up to 1 week after last study dose (1 week after end of Period 2)]

    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.

11. Treatment Duration [Day 1 up to Day 21]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Subjects with a diagnosis of Attention Deficit Hyperactivity Disorder, based on clinical assessment and interview.

Male and female outpatients. Subjects with a diagnosis of Attention Deficit Hyperactivity Disorder, based on clinical assessment and interview.

Female subjects must be of non-childbearing potential.

Exclusion Criteria:

Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular (including hypertension), hepatic, neurologic, or allergic disease.

Current or lifetime history of psychosis or bipolar disorder; any current anxiety disorder (with the exception of social or specific phobia), or substance abuse or dependence in the past 6 months.

Current episode of Major Depression or episode within the last 6 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bay Area Research Institute	Lafayette	California	United States	94549
2	Pharmacology Research Institute	Los Alamitos	California	United States	90720
3	Pharmacology Research Institute	Newport Beach	California	United States	92660
4	The University of Illinois at Chicago, Institute for Juvenile Research	Chicago	Illinois	United States	60608
5	Massachusetts General Hospital, ADHD Program	Cambridge	Massachusetts	United States	02138
6	New York University School of Medicine	New York	New York	United States	10010
7	NeuroScience, Inc	Herndon	Virginia	United States	20170

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00531752
• Other Study ID Numbers: A8801004; 3-WK, CO MTD IN ADULTS W/ADHD
• First Posted: Sep 19, 2007
• Last Update Posted: Feb 19, 2016
• Last Verified: Jan 1, 2016

• Additional relevant MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity

Study Results

Participant Flow

Arm/Group Title	Placebo First, Then PF-03654746 (Low Dose)	PF-03654746 (Low Dose) First, Then Placebo	Placebo First, Then PF-03654746 (Flexible Dose)	PF-03654746 (Flexible Dose) First, Then Placebo
Arm/Group Description	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.	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 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 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.
Period Title: First Double-blind Intervention Period
STARTED	17	17	16	16
Treated	16	17	16	16
COMPLETED	11	13	9	13
NOT COMPLETED	6	4	7	3
Period Title: First Double-blind Intervention Period
STARTED	11	13	9	13
COMPLETED	11	13	9	13
NOT COMPLETED	0	0	0	0
Period Title: First Double-blind Intervention Period
STARTED	11	13	9	13
COMPLETED	9	11	9	11
NOT COMPLETED	2	2	0	2

Baseline Characteristics

Arm/Group Title	Placebo First, Then PF-03654746 (Low Dose)	PF-03654746 (Low Dose) First, Then Placebo	Placebo First, Then PF-03654746 (Flexible Dose)	PF-03654746 (Flexible Dose) First, Then Placebo	Total
Arm/Group Description	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.	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 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 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 of all reporting groups
Overall Participants	16	17	16	16	65
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.3 (12.6)	38.4 (10.6)	37.9 (10.2)	35.9 (9.6)	37.4 (10.6)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%
Male	16 100%	17 100%	16 100%	16 100%	65 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Adult Attention Deficit Hyperactivity Disorder (ADHD) Investigator Symptom Rating Scale (AISRS) Total Score at Week 3
Description	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.
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	27	22	52
Baseline (n=27, 22, 52)	36.778 (8.5545)	38.273 (4.8715)	36.135 (7.3592)
Change at Week 3 (n=25, 21, 48)	-7.196 (8.7318)	-5.745 (9.9824)	-6.789 (8.5734)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6749
	Comments	P-values are not adjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean Difference
	Estimated Value	0.7947
	Confidence Interval	(2-Sided) 80%; -1.649 to 3.2383
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.8848
	Estimation Comments	Positive value for the LS mean difference indicates the estimate favors placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4886
	Comments	P-values are not adjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.4176
	Confidence Interval	(2-Sided) 80%; -1.218 to 4.0533
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.0343
	Estimation Comments	Positive value for the LS mean difference indicates the estimate favors placebo.

2. Secondary Outcome

Title	Change From Baseline in Adult Attention Deficit Hyperactivity Disorder (ADHD) Investigator Symptom Rating Scale (AISRS) Total Score at Week 1 and 2
Description	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.
Time Frame	Baseline, Week 1, 2

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	26	22	50
Week 1 (n=26, 22, 50)	-4.942 (6.2005)	-3.591 (8.3476)	-5.524 (7.4545)
Week 2 (n=23, 20, 46)	-6.022 (7.1486)	-5.7 (7.8143)	-7.109 (6.6139)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 1: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5643
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.0250
	Confidence Interval	(2-Sided) 80%; -1.262 to 3.3121
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.7713
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 1: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3107
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.9146
	Confidence Interval	(2-Sided) 80%; -0.5100 to 4.3392
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.8777
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 2: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1196
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.3154
	Confidence Interval	(2-Sided) 80%; 0.41601 to 4.2148
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.4638
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 2: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3872
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.3288
	Confidence Interval	(2-Sided) 80%; -0.6490 to 3.3065
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.5240
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With at Least 30 Percent Decrease From Baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) Total Score
Description	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.
Time Frame	Week 1, 2, 3

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	26	22	50
Week 1 (n=26, 22, 50)	15.385 96.2%	13.636 80.2%	24 150%
Week 2 (n=23, 20, 46)	26.087 163%	30 176.5%	30.435 190.2%
Week 3 (n=25, 21, 48)	24 150%	23.81 140.1%	29.167 182.3%

4. Secondary Outcome

Title	Percentage of Participants With 1 or 2 Score on Clinical Global Impression-Severity Scale (CGI-S)
Description	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.
Time Frame	Week 1, 2, 3

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	26	22	50
Week 1 (n=26, 22, 50)	3.846 24%	4.545 26.7%	2 12.5%
Week 2 (n=23, 20, 49)	0.0 0%	5 29.4%	4.082 25.5%
Week 3 (n=25, 21, 50)	8 50%	4.762 28%	6 37.5%

5. Secondary Outcome

Title	Percentage of Participants With Less Than or Equal to 18 Score on Adult ADHD Investigator Symptom Rating Scale (AISRS)
Description	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.
Time Frame	Week 1, 2, 3

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	26	22	50
Week 1 (n=26, 22, 50)	11.538 72.1%	4.545 26.7%	14 87.5%
Week 2 (n=23, 20, 46)	21.739 135.9%	10 58.8%	13.043 81.5%
Week 3 (n=25, 21, 48)	16 100%	14.286 84%	16.667 104.2%

6. Secondary Outcome

Title	Percentage of Participants With Sustained Response of at Least 30 Percent Decrease From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score
Description	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.
Time Frame	Day 7, 14, 21

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	21	18	45
Day 7 (n=21, 18, 45)	38.095 238.1%	27.778 163.4%	33.333 208.3%
Day 14 (n=17, 16, 35)	23.529 147.1%	31.25 183.8%	31.429 196.4%
Day 21 (n=9, 6, 22)	33.333 208.3%	16.667 98%	40.909 255.7%

7. Secondary Outcome

Title	Change From Baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) Subscale Scores at Week 1, 2 and 3
Description	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.
Time Frame	Baseline, Week 1, 2, 3

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	26	22	50
Week 1: Inattention (n=26, 22, 50)	-3.423 (3.6241)	-1.636 (4.7338)	-3.36 (4.3986)
Week 2: Inattention (n=23, 20, 46)	-4.326 (5.2627)	-2.65 (4.5541)	-4.022 (4.2985)
Week 3: Inattention (n=25, 21, 48)	-4.085 (5.7909)	-3.31 (5.8019)	-3.719 (5.195)
Week 1: Hyperactivity/Impulsivity (n=26, 22, 50)	-1.519 (3.708)	-1.955 (4.0027)	-2.164 (3.7001)
Week 2: Hyperactivity/Impulsivity (n=23, 20, 46)	-1.696 (3.1935)	-3.05 (3.9766)	-3.087 (3.2614)
Week 3: Hyperactivity/Impulsivity (n=25, 21, 48)	-3.111 (4.1894)	-2.435 (4.8666)	-3.07 (4.2411)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 1 (Inattention): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8708
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1677
	Confidence Interval	(2-Sided) 80%; -1.162 to 1.4971
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.0269
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 1 (Inattention): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0927
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.8607
	Confidence Interval	(2-Sided) 80%; 0.44874 to 3.2726
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.0912
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 1 (Hyperactivity/Impulsivity): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3405
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.8660
	Confidence Interval	(2-Sided) 80%; -0.3008 to 2.0329
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.9037
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 1 (Hyperactivity/Impulsivity): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8665
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1623
	Confidence Interval	(2-Sided) 80%; -1.080 to 1.4047
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.9622
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 2 (Inattention): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6901
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.3886
	Confidence Interval	(2-Sided) 80%; -0.8694 to 1.6466
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.9694
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 2 (Inattention): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1790
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.3779
	Confidence Interval	(2-Sided) 80%; 0.06498 to 2.6908
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.0114
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 2 (Hyperactivity/Impulsivity): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0156
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.8759
	Confidence Interval	(2-Sided) 80%; 0.90156 to 2.8502
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7508
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 2 (Hyperactivity/Impulsivity): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9573
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04217
	Confidence Interval	(2-Sided) 80%; -1.060 to 0.97559
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7842
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (Inattention): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8986
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1602
	Confidence Interval	(2-Sided) 80%; -1.462 to 1.7820
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.2517
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (Inattention): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6204
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.6688
	Confidence Interval	(2-Sided) 80%; -1.071 to 2.4086
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.3437
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (Hyperactivity/Impulsivity): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5759
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.4920
	Confidence Interval	(2-Sided) 80%; -0.6421 to 1.6261
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.8742
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (Hyperactivity/Impulsivity): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3603
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.8750
	Confidence Interval	(2-Sided) 80%; -0.3552 to 2.1051
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.9488
	Estimation Comments

8. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline, Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 21

Outcome Measure Data

Analysis Population Description

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.

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

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Day 1: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0392
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.5306
	Confidence Interval	(2-Sided) 80%; 1.3659 to 5.6952
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.6664
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Day 1: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	6.9344
	Confidence Interval	(2-Sided) 80%; 4.6177 to 9.2512
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.7848
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Day 2: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0547
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.2888
	Confidence Interval	(2-Sided) 80%; 1.4544 to 7.1232
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.1861
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Day 2: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0176
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.6799
	Confidence Interval	(2-Sided) 80%; 2.6655 to 8.6943
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.3261
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Day 3: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7750
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.7203
	Confidence Interval	(2-Sided) 80%; -2.530 to 3.9704
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.5085
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Day 3: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9874
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04276
	Confidence Interval	(2-Sided) 80%; -3.521 to 3.4357
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.6874
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Day 4: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7799
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.6252
	Confidence Interval	(2-Sided) 80%; -3.513 to 2.2629
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.2268
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Day 4: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1881
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.1136
	Confidence Interval	(2-Sided) 80%; 0.08338 to 6.1438
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.3365
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Day 5: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4032
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.6575
	Confidence Interval	(2-Sided) 80%; -0.8944 to 4.2094
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.9677
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Day 5: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0059
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.9254
	Confidence Interval	(2-Sided) 80%; 3.2314 to 8.6193
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.0796
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Day 6: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6067
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.0921
	Confidence Interval	(2-Sided) 80%; -1.643 to 3.8273
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.1098
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Day 6: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0614
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.2785
	Confidence Interval	(2-Sided) 80%; 1.3709 to 7.1860
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.2424
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Day 7: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7476
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.7149
	Confidence Interval	(2-Sided) 80%; -3.584 to 2.1546
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.2086
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Day 7: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5863
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.3355
	Confidence Interval	(2-Sided) 80%; -4.499 to 1.8284
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.4396
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Day 8: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9591
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1058
	Confidence Interval	(2-Sided) 80%; -2.771 to 2.5593
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.0529
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Day 8: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8442
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4352
	Confidence Interval	(2-Sided) 80%; -3.294 to 2.4238
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.2048
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Day 9: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1977
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.6876
	Confidence Interval	(2-Sided) 80%; 0.01391 to 5.3613
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.0533
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Day 9: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4235
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.8149
	Confidence Interval	(2-Sided) 80%; -1.108 to 4.7375
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.2467
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Day 10: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1882
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.6424
	Confidence Interval	(2-Sided) 80%; 0.07015 to 5.2147
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.9753
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Day 10: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5555
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.2105
	Confidence Interval	(2-Sided) 80%; -1.440 to 3.8615
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.0376
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Day 11: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1533
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.1804
	Confidence Interval	(2-Sided) 80%; 0.33169 to 6.0292
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.1934
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Day 11: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3697
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.0511
	Confidence Interval	(2-Sided) 80%; -0.8912 to 4.9934
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.2662
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Day 12: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4652
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.7640
	Confidence Interval	(2-Sided) 80%; -1.352 to 4.8801
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.3939
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Day 12: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8626
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.4377
	Confidence Interval	(2-Sided) 80%; -2.830 to 3.7058
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.5148
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Day 13: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0261
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.7114
	Confidence Interval	(2-Sided) 80%; 1.6105 to 5.8122
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.6168
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Day 13: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1895
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.2644
	Confidence Interval	(2-Sided) 80%; 0.05330 to 4.4756
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.7026
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Day 14: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4994
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.1151
	Confidence Interval	(2-Sided) 80%; -1.961 to 6.1913
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.0732
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Day 14: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2945
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.5616
	Confidence Interval	(2-Sided) 80%; -0.8226 to 7.9458
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.3113
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Day 21: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8056
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.7306
	Confidence Interval	(2-Sided) 80%; -4.622 to 3.1613
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.9257
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Day 21: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3922
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.3672
	Confidence Interval	(2-Sided) 80%; -1.725 to 8.4592
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.8657
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Week 3
Description	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.
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	27	22	52
Baseline (n=27, 22, 52)	6.63 (3.9918)	7.773 (5.0231)	6.962 (4.5631)
Change at Week 3 (n=21, 19, 42)	-2.19 (3.9353)	-1.289 (3.728)	-0.524 (5.1572)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0913
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.5069
	Confidence Interval	(2-Sided) 80%; -2.643 to -0.3705
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.8744
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Day 3: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8216
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2078
	Confidence Interval	(2-Sided) 80%; -1.399 to 0.98326
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.9165
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Week 3
Description	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.
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	27	22	52
Baseline (n=27, 22, 52)	5.333 (3.9223)	6.045 (3.848)	5.327 (3.3238)
Change at Week 3 (n=18, 21, 39)	-0.944 (2.514)	-0.19 (2.5518)	-0.487 (2.7732)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5466
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4181
	Confidence Interval	(2-Sided) 80%; -1.313 to 0.47668
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.6887
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9705
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.02518
	Confidence Interval	(2-Sided) 80%; -0.9035 to 0.85312
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.6772
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3
Description	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.
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description

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.

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

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (CQoL): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7415
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.09953
	Confidence Interval	(2-Sided) 80%; -0.4892 to 0.29012
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3001
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (CQoL): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8822
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.04804
	Confidence Interval	(2-Sided) 80%; -0.3703 to 0.46640
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3227
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (GLI): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3414
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1250
	Confidence Interval	(2-Sided) 80%; -0.0439 to 0.29385
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1302
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (GLI): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4642
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1044
	Confidence Interval	(2-Sided) 80%; -0.0793 to 0.28814
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1418
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (RTI): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5049
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.06109
	Confidence Interval	(2-Sided) 80%; -0.0571 to 0.17926
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09093
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (RTI): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4332
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.07917
	Confidence Interval	(2-Sided) 80%; -0.0510 to 0.20930
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1002
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (More GD than BD): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1678
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2453
	Confidence Interval	(2-Sided) 80%; -0.4730 to -0.0177
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1753
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (More GD than BD): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6901
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.07717
	Confidence Interval	(2-Sided) 80%; -0.1726 to 0.32695
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1925
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (Living with ADHD): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9005
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1702
	Confidence Interval	(2-Sided) 80%; -1.587 to 1.9274
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.3540
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (Living with ADHD): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3330
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.4317
	Confidence Interval	(2-Sided) 80%; -3.333 to 0.46937
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.4667
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (General well-being): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7551
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.6537
	Confidence Interval	(2-Sided) 80%; -2.051 to 3.3584
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.0857
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (General well-being): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0334
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-4.8639
	Confidence Interval	(2-Sided) 80%; -7.759 to -1.968
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.2354
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (PDF): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6519
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.6389
	Confidence Interval	(2-Sided) 80%; -3.050 to 6.3281
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.6119
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (PDF): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7631
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.2007
	Confidence Interval	(2-Sided) 80%; -3.941 to 6.3423
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.9647
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (R/C): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3034
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.9211
	Confidence Interval	(2-Sided) 80%; -0.7227 to 6.5648
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.8206
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (R/C): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0933
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.0968
	Confidence Interval	(2-Sided) 80%; -8.975 to -1.218
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.0022
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (IS-B/C): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0949
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.0675
	Confidence Interval	(2-Sided) 80%; -8.934 to -1.201
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.9778
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (IS-B/C): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0283
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-7.3274
	Confidence Interval	(2-Sided) 80%; -11.55 to -3.106
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.2552
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (IS-I): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1852
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.1505
	Confidence Interval	(2-Sided) 80%; -4.229 to -0.0719
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.5974
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (IS-I): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1623
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.5178
	Confidence Interval	(2-Sided) 80%; -4.823 to -0.2127
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.7732
	Estimation Comments

12. Secondary Outcome

Title	Change From Baseline in Adult ADHD Quality of Life Scale (AAQOL) Subscale Score at Week 3
Description	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.
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	27	22	52
Baseline: Life productivity (n=27, 22, 52)	306.481 (109.9809)	292.045 (72.5334)	281.25 (107.9982)
Baseline: Psychological health (n=27, 22, 52)	163.889 (42.9296)	146.591 (66.0517)	167.788 (59.4782)
Baseline: Life outlook (n=27, 22, 52)	229.63 (65.7929)	194.318 (69.8348)	218.269 (59.0188)
Baseline: Relationships (n=27, 22, 52)	152.778 (49.1922)	154.545 (46.0566)	163.942 (49.856)
Change at Week 3: Life productivity (n=25, 21, 47)	3 (84.1068)	8.333 (112.7312)	22.606 (85.7606)
Change at Week 3: PH (n=25, 21, 47)	0 (50.5181)	1.786 (57.1847)	11.436 (63.9415)
Change at Week 3: Life outlook (n=25, 21, 47)	-13 (56.9951)	14.286 (68.9526)	-8.511 (42.6776)
Change at Week 3: Relationships (n=25, 21, 47)	-1.5 (31.9342)	1.19 (46.2508)	-3.723 (45.662)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (Life productivity): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5241
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-11.5791
	Confidence Interval	(2-Sided) 80%; -35.02 to 11.860
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 18.0449
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (Life productivity): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3065
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-20.3367
	Confidence Interval	(2-Sided) 80%; -45.89 to 5.2183
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 19.6995
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (Psychological health): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3831
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-11.7878
	Confidence Interval	(2-Sided) 80%; -29.15 to 5.5793
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 13.4438
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (Psychological health): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3657
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-13.1401
	Confidence Interval	(2-Sided) 80%; -31.80 to 5.5241
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 14.4478
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (Life outlook): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8188
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.6660
	Confidence Interval	(2-Sided) 80%; -12.36 to 17.690
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 11.5818
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (Life outlook): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0566
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	24.1011
	Confidence Interval	(2-Sided) 80%; 8.0305 to 40.172
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 12.4050
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (Relationships): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9312
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.7559
	Confidence Interval	(2-Sided) 80%; -10.55 to 12.057
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.7164
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (Relationships): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5194
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	6.1138
	Confidence Interval	(2-Sided) 80%; -6.108 to 18.336
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.4361
	Estimation Comments

13. Secondary Outcome

Title	Change From Baseline in Sheehan Disability Scale (SDS) Subscale Scores at Week 3
Description	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.
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	27	22	52
Baseline: Work/school (n=26, 21, 50)	6.058 (2.2375)	6.095 (2.0894)	6.36 (1.977)
Baseline: Social life (n=27, 22, 52)	4.593 (2.0383)	5.227 (2.5153)	5.01 (2.0757)
Baseline: Family life/home (n=27, 22, 52)	5.019 (2.0357)	5.705 (2.0393)	5.673 (1.8335)
Change at Week 3: Work/school (n=24, 18, 45)	-0.813 (1.3089)	-0.222 (2.2572)	-0.411 (1.7526)
Change at Week 3: Social life (n=25, 21, 47)	-0.8 (1.75)	-0.619 (2.4592)	-0.436 (1.9043)
Change at Week 3: Family life/home (n=25, 21, 47)	-0.78 (1.5618)	-0.071 (2.2709)	-0.532 (1.6596)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (Work/school): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3320
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3255
	Confidence Interval	(2-Sided) 80%; -0.7573 to 0.10622
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3320
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (Work/school): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2767
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.4255
	Confidence Interval	(2-Sided) 80%; -0.0769 to 0.92804
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3871
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (Social life): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3675
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3661
	Confidence Interval	(2-Sided) 80%; -0.8887 to 0.15660
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4028
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (Social life): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8141
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1033
	Confidence Interval	(2-Sided) 80%; -0.6700 to 0.46345
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4372
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (Family life/home): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6186
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1854
	Confidence Interval	(2-Sided) 80%; -0.6657 to 0.29495
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3702
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (Family life/home): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3720
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.3623
	Confidence Interval	(2-Sided) 80%; -0.1597 to 0.88432
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4028
	Estimation Comments

14. Other Pre-specified Outcome

Title	Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3
Description	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.
Time Frame	Baseline, Week 1, 2, 3

Outcome Measure Data

Analysis Population Description

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.

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

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 1 (Sleep disturbance): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	25.0781
	Confidence Interval	(2-Sided) 80%; 18.565 to 31.591
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.0238
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 1 (Sleep disturbance): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0049
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	15.6481
	Confidence Interval	(2-Sided) 80%; 8.7110 to 22.585
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.3551
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 1 (Snoring): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3078
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.6270
	Confidence Interval	(2-Sided) 80%; -8.196 to 0.94237
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.5248
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 1 (Snoring): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0644
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.1594
	Confidence Interval	(2-Sided) 80%; 2.2344 to 12.084
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.8022
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 1 (ASoB): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1517
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.5601
	Confidence Interval	(2-Sided) 80%; 0.49198 to 8.6281
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.1318
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 1 (ASoB): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8252
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.7384
	Confidence Interval	(2-Sided) 80%; -5.056 to 3.5789
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.3281
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 1 (Sleep quantity): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0063
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.6228
	Confidence Interval	(2-Sided) 80%; -0.9082 to -0.3375
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2203
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 1 (Sleep quantity): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3217
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2301
	Confidence Interval	(2-Sided) 80%; -0.5283 to 0.06822
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2303
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 1 (Optimal sleep): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2307
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1291
	Confidence Interval	(2-Sided) 80%; -0.0091 to 0.26716
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1065
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 1 (Optimal sleep): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4585
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.08114
	Confidence Interval	(2-Sided) 80%; -0.0598 to 0.22209
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1087
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 1 (Sleep adequacy): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3477
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.6629
	Confidence Interval	(2-Sided) 80%; -8.681 to 1.3549
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.8642
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 1 (Sleep adequacy): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1565
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.8688
	Confidence Interval	(2-Sided) 80%; -11.17 to -0.5693
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.0842
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 1 (Somnolence): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1088
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.4319
	Confidence Interval	(2-Sided) 80%; -11.55 to -1.311
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.9541
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 1 (Somnolence): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8627
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.7208
	Confidence Interval	(2-Sided) 80%; -4.654 to 6.0952
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.1517
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 1 (SPI I): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0024
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	56.6310
	Confidence Interval	(2-Sided) 80%; 33.532 to 79.730
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 17.8056
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 1 (SPI I): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0112
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	49.1543
	Confidence Interval	(2-Sided) 80%; 24.831 to 73.478
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 18.7622
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 1 (SPI II): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	10.9197
	Confidence Interval	(2-Sided) 80%; 6.9105 to 14.929
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.0912
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 1 (SPI II): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0129
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	8.4691
	Confidence Interval	(2-Sided) 80%; 4.1876 to 12.751
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.3037
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 2 (Sleep disturbance): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0020
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	14.1078
	Confidence Interval	(2-Sided) 80%; 8.4492 to 19.766
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.3667
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 2 (Sleep disturbance): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0026
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	14.3485
	Confidence Interval	(2-Sided) 80%; 8.4275 to 20.270
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.5692
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 2 (Snoring): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9305
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2989
	Confidence Interval	(2-Sided) 80%; -4.729 to 4.1309
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.4103
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 2 (Snoring): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1178
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.7062
	Confidence Interval	(2-Sided) 80%; -10.36 to -1.050
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.5839
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 2 (ASoB): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3339
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.4586
	Confidence Interval	(2-Sided) 80%; -0.8124 to 5.7295
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.5231
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 2 (ASoB): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0698
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.8590
	Confidence Interval	(2-Sided) 80%; 1.4493 to 8.2686
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.6300
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 2 (Sleep quantity): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0762
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3364
	Confidence Interval	(2-Sided) 80%; -0.5777 to -0.0950
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1859
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 2 (Sleep quantity): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4096
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1591
	Confidence Interval	(2-Sided) 80%; -0.4075 to 0.08935
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1913
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 2 (Optimal sleep): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0455
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.2115
	Confidence Interval	(2-Sided) 80%; 0.07751 to 0.34550
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1033
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 2 (Optimal sleep): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4585
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.08114
	Confidence Interval	(2-Sided) 80%; -0.0598 to 0.22209
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1087
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 2 (Sleep adequacy): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9078
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.5433
	Confidence Interval	(2-Sided) 80%; -5.513 to 6.5995
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.6662
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 2 (Sleep adequacy): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6502
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.1848
	Confidence Interval	(2-Sided) 80%; -8.403 to 4.0338
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.7892
	Estimation Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 2 (Somnolence): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8090
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.9029
	Confidence Interval	(2-Sided) 80%; -5.716 to 3.9101
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.7234
	Estimation Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 2 (Somnolence): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5282
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.4351
	Confidence Interval	(2-Sided) 80%; -2.532 to 7.4025
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.8429
	Estimation Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 2 (SPI I): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1848
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	25.3231
	Confidence Interval	(2-Sided) 80%; 0.86393 to 49.782
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 18.8604
	Estimation Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 2 (SPI I): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0124
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	50.4054
	Confidence Interval	(2-Sided) 80%; 25.134 to 75.677
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 19.4810
	Estimation Comments

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 2 (SPI II): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0267
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	6.8658
	Confidence Interval	(2-Sided) 80%; 2.9504 to 10.781
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.0205
	Estimation Comments

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 2 (SPI II): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0134
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	8.0855
	Confidence Interval	(2-Sided) 80%; 3.9787 to 12.192
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.1677
	Estimation Comments

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (Sleep disturbance): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0152
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	9.5242
	Confidence Interval	(2-Sided) 80%; 4.5949 to 14.453
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.7993
	Estimation Comments

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (Sleep disturbance): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	19.9806
	Confidence Interval	(2-Sided) 80%; 14.602 to 25.359
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.1501
	Estimation Comments

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (Snoring): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3516
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.7667
	Confidence Interval	(2-Sided) 80%; -6.590 to 1.0562
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.9402
	Estimation Comments

Statistical Analysis 40

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (Snoring): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3448
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.0838
	Confidence Interval	(2-Sided) 80%; -1.116 to 7.2838
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.2323
	Estimation Comments

Statistical Analysis 41

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (ASoB): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5583
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.5882
	Confidence Interval	(2-Sided) 80%; -8.294 to 3.1175
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.3902
	Estimation Comments

Statistical Analysis 42

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (ASoB): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1141
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.6547
	Confidence Interval	(2-Sided) 80%; 1.4717 to 13.838
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.7652
	Estimation Comments

Statistical Analysis 43

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (Sleep quantity): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0034
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.5882
	Confidence Interval	(2-Sided) 80%; -0.8356 to -0.3408
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1903
	Estimation Comments

Statistical Analysis 44

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (Sleep quantity): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4083
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1722
	Confidence Interval	(2-Sided) 80%; -0.4403 to 0.09599
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2064
	Estimation Comments

Statistical Analysis 45

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (Optimal sleep): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0120
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.2744
	Confidence Interval	(2-Sided) 80%; 0.13746 to 0.41127
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1055
	Estimation Comments

Statistical Analysis 46

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (Optimal sleep): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3750
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1016
	Confidence Interval	(2-Sided) 80%; -0.0457 to 0.24881
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1136
	Estimation Comments

Statistical Analysis 47

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (Sleep adequacy): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9119
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.4367
	Confidence Interval	(2-Sided) 80%; -4.665 to 5.5387
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.9301
	Estimation Comments

Statistical Analysis 48

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (Sleep adequacy): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1367
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.3429
	Confidence Interval	(2-Sided) 80%; -11.79 to -0.8960
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.1977
	Estimation Comments

Statistical Analysis 49

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (Somnolence): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0595
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.0062
	Confidence Interval	(2-Sided) 80%; -10.05 to -1.964
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.1094
	Estimation Comments

Statistical Analysis 50

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (Somnolence): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1356
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.0362
	Confidence Interval	(2-Sided) 80%; 0.72505 to 9.3473
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.3182
	Estimation Comments

Statistical Analysis 51

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (SPI I): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7528
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.1569
	Confidence Interval	(2-Sided) 80%; -15.99 to 26.303
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 16.2884
	Estimation Comments

Statistical Analysis 52

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (SPI I): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	67.7022
	Confidence Interval	(2-Sided) 80%; 45.114 to 90.290
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 17.4066
	Estimation Comments

Statistical Analysis 53

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3 (SPI II): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2837
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.8582
	Confidence Interval	(2-Sided) 80%; -0.5670 to 6.2835
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.6389
	Estimation Comments

Statistical Analysis 54

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3 (SPI II): Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	12.9251
	Confidence Interval	(2-Sided) 80%; 9.1761 to 16.674
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.8913
	Estimation Comments

15. Other Pre-specified Outcome

Title	Change From Baseline in Subjective Sleep Questionnaire (SSQ) Latency Subscale Scores at Week 1, 2 and 3
Description	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.
Time Frame	Baseline, Week 1, 2, 3

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	27	22	52
Baseline (n=27, 22, 52)	30.333 (35.7464)	31.364 (29.7582)	29.067 (31.8087)
Change at Week 1 (n=25, 22, 43)	24.6 (89.6858)	-3.409 (46.2302)	0.837 (60.9442)
Change at Week 2 (n=21, 19, 43)	-3.024 (23.4763)	-12.632 (31.1858)	-11.105 (23.2396)
Change at Week 3 (n=18, 11, 36)	-3.222 (36.2086)	4.091 (66.954)	-11.958 (30.2856)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 1: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	26.8615
	Confidence Interval	(2-Sided) 80%; 21.777 to 31.946
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.9167
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 1: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3034
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.3455
	Confidence Interval	(2-Sided) 80%; -1.080 to 9.7713
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.1817
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 2: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0223
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	6.9558
	Confidence Interval	(2-Sided) 80%; 3.1320 to 10.780
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.9408
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 2: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2284
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.7518
	Confidence Interval	(2-Sided) 80%; -0.2442 to 7.7479
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.0743
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0201
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	8.5752
	Confidence Interval	(2-Sided) 80%; 3.9265 to 13.224
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.5848
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1931
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.0229
	Confidence Interval	(2-Sided) 80%; 0.07753 to 9.9683
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.8154
	Estimation Comments

16. Other Pre-specified Outcome

Title	Change From Baseline in Subjective Sleep Questionnaire (SSQ) Hours of Sleep Subscale Scores at Week 1, 2 and 3
Description	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.
Time Frame	Baseline, Week 1, 2, 3

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	27	22	52
Baseline (n=27, 22, 52)	6.05 (1.0963)	6.48 (1.2806)	6.364 (1.2534)
Change at Week 1 (n=25, 22, 43)	0.147 (1.4865)	0.414 (2.0816)	0.763 (1.5914)
Change at Week 2 (21, 19, 43)	0.414 (1.2911)	0.319 (1.7)	0.865 (1.4959)
Change at Week 3 (n=18, 11, 36)	-0.148 (1.7562)	-0.17 (2.0091)	0.717 (1.2305)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 1: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.6766
	Confidence Interval	(2-Sided) 80%; -0.9046 to -0.4487
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1759
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 1: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1055
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3075
	Confidence Interval	(2-Sided) 80%; -0.5499 to -0.0650
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1871
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 2: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0119
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4684
	Confidence Interval	(2-Sided) 80%; -0.7012 to -0.2356
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1791
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 2: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5016
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1263
	Confidence Interval	(2-Sided) 80%; -0.3687 to 0.11608
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1866
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0531
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3451
	Confidence Interval	(2-Sided) 80%; -0.5711 to -0.1191
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1738
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0306
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4137
	Confidence Interval	(2-Sided) 80%; -0.6549 to -0.1725
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1856
	Estimation Comments

17. Other Pre-specified Outcome

Title	Change From Baseline in Subjective Sleep Questionnaire (SSQ) Number of Awakenings Subscale Scores at Week 1, 2 and 3
Description	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.
Time Frame	Baseline, Week 1, 2, 3

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	27	22	52
Baseline (n=27, 22, 52)	1.37 (1.4317)	1.182 (1.0065)	1.298 (1.2258)
Change at Week 1 (n=25, 22, 43)	0.12 (1.6788)	0.5 (1.7252)	-0.209 (1.4402)
Change at Week 2 (n=21, 19, 43)	-0.333 (1.977)	0.158 (1.2589)	-0.419 (1.2293)
Change at Week 3 (n=18, 11, 36)	0.028 (2.0398)	0.045 (1.4222)	-0.361 (1.2627)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 1: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.7671
	Confidence Interval	(2-Sided) 80%; 0.54260 to 0.99157
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1731
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 1: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0059
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.5285
	Confidence Interval	(2-Sided) 80%; 0.28911 to 0.76798
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1847
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 2: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2921
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1526
	Confidence Interval	(2-Sided) 80%; -0.0336 to 0.33878
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1431
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 2: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1929
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1980
	Confidence Interval	(2-Sided) 80%; 0.00319 to 0.39272
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1498
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0332
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.3433
	Confidence Interval	(2-Sided) 80%; 0.13988 to 0.54663
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1565
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0162
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.4184
	Confidence Interval	(2-Sided) 80%; 0.20006 to 0.63674
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1681
	Estimation Comments

18. Other Pre-specified Outcome

Title	Change From Baseline in Subjective Sleep Questionnaire (SSQ) Total Awake After Sleep Onset (WASO) Subscale Scores at Week 1, 2 and 3
Description	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.
Time Frame	Baseline, Week 1, 2, 3

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	27	22	52
Baseline (n=27, 22, 52)	0.432 (0.6295)	0.578 (0.8214)	0.529 (0.7442)
Change at Week 1 (25, 22, 43)	0.109 (0.5542)	0.013 (1.2797)	-0.286 (0.7444)
Change at Week 2 (n=21, 19, 43)	-0.133 (0.7064)	-0.167 (0.8035)	-0.228 (0.8409)
Change at Week 3 (n=18, 11, 36)	0.091 (0.6291)	0.329 (1.3329)	-0.313 (0.6863)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 1: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.5103
	Confidence Interval	(2-Sided) 80%; 0.36707 to 0.65345
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1103
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 1: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0031
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.3643
	Confidence Interval	(2-Sided) 80%; 0.21189 to 0.51664
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1174
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 2: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1553
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1362
	Confidence Interval	(2-Sided) 80%; 0.01366 to 0.25882
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09408
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 2: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2809
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1070
	Confidence Interval	(2-Sided) 80%; -0.0205 to 0.23458
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09797
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0603
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.2195
	Confidence Interval	(2-Sided) 80%; 0.07101 to 0.36803
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1146
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.4278
	Confidence Interval	(2-Sided) 80%; 0.27079 to 0.58479
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1212
	Estimation Comments

19. Other Pre-specified Outcome

Title	Change From Baseline in Subjective Sleep Questionnaire (SSQ) Quality of Sleep Subscale Scores at Week 1, 2 and 3
Description	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.
Time Frame	Baseline, Week 1, 2, 3

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	27	22	52
Baseline (n=27, 22, 52)	57.093 (19.7582)	55 (23.4663)	56.202 (20.9533)
Change at Week 1 (n=25, 22, 42)	-4.06 (21.0616)	0.5 (25.6715)	8.393 (25.5447)
Change at Week 2 (n=21, 19, 43)	8.286 (22.3375)	11.105 (22.6124)	9.43 (20.5434)
Change at Week 3 (n=18, 11, 36)	7.222 (21.7764)	0.182 (44.302)	10.389 (22.8602)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 1: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-13.3264
	Confidence Interval	(2-Sided) 80%; -16.83 to -9.828
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.6944
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 1: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0068
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-8.1260
	Confidence Interval	(2-Sided) 80%; -11.87 to -4.382
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.8841
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 2: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1346
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.5341
	Confidence Interval	(2-Sided) 80%; -6.551 to -0.5175
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.3172
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 2: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6552
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.0911
	Confidence Interval	(2-Sided) 80%; -2.067 to 4.2494
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.4268
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Low Dose), Placebo
	Comments	Week 3: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0765
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.2001
	Confidence Interval	(2-Sided) 80%; -5.494 to -0.9063
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.7614
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 (Flexible Dose), Placebo
	Comments	Week 3: Mixed effects linear model was used with treatment, period and investigator as fixed effects; baseline as covariate and participants as random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0473
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.8781
	Confidence Interval	(2-Sided) 80%; -6.349 to -1.407
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.8976
	Estimation Comments

20. Other Pre-specified Outcome

Title	Number of Participants With Clinically Significant Laboratory Test Abnormalities
Description	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).
Time Frame	Baseline up to 1 week after last study dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	28	25	55
Number [participants]	5 31.3%	9 52.9%	10 62.5%

21. Other Pre-specified Outcome

Title	Number of Participants With Electrocardiogram (ECG) Findings
Description	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.
Time Frame	Baseline up to End of Treatment (Week 3 of period 2)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	28	25	57
Number [participants]	1 6.3%	0 0%	1 6.3%

22. Other Pre-specified Outcome

Title	Number of Participants With Clinically Significant Vital Sign Abnormalities
Description	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.
Time Frame	Baseline up to 1 week after last study dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	28	25	55
Number [participants]	0 0%	0 0%	1 6.3%

23. Other Pre-specified Outcome

Title	Number of Participants With Change From Baseline in Physical Examination and Neurological Examination
Description	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.
Time Frame	Baseline up to 1 week after last study dose (1 week after end of Period 2)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	28	25	58
Number [participants]	0 0%	0 0%	0 0%

24. Other Pre-specified Outcome

Title	Treatment Duration
Description	Treatment duration was defined as the total number of dosing days from first to last day of study drug administration in each period.
Time Frame	Day 1 up to Day 21

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PF-03654746 (Low Dose)	PF-03654746 (Flexible Dose)	Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.	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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
Measure Participants	28	25	58
Mean (Full Range) [days]	21	21	21

Adverse Events

Adverse Event Reporting Description	Safety analysis population included all participants who received at least 1 dose of study medication.
Arm/Group Title	PF-03654746 (Low Dose)		PF-03654746 (Flexible Dose)		Placebo
Arm/Group Description	PF-03654746 capsule 1 mg orally once daily for 3 weeks in first or second DB intervention period.		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 matched to PF-03654746 orally once daily for 3 weeks in first or second DB intervention period.
All Cause Mortality
	PF-03654746 (Low Dose)		PF-03654746 (Flexible Dose)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	PF-03654746 (Low Dose)		PF-03654746 (Flexible Dose)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/25 (0%)		0/58 (0%)
Other (Not Including Serious) Adverse Events
	PF-03654746 (Low Dose)		PF-03654746 (Flexible Dose)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/28 (75%)		19/25 (76%)		33/58 (56.9%)
Cardiac disorders
Palpitations	1/28 (3.6%)		1/25 (4%)		0/58 (0%)
Ear and labyrinth disorders
Hyperacusis	1/28 (3.6%)		0/25 (0%)		0/58 (0%)
Eye disorders
Conjunctivitis	0/28 (0%)		0/25 (0%)		1/58 (1.7%)
Lacrimation increased	0/28 (0%)		0/25 (0%)		1/58 (1.7%)
Vision blurred	0/28 (0%)		0/25 (0%)		1/58 (1.7%)
Gastrointestinal disorders
Abdominal discomfort	0/28 (0%)		0/25 (0%)		1/58 (1.7%)
Constipation	2/28 (7.1%)		0/25 (0%)		2/58 (3.4%)
Diarrhoea	0/28 (0%)		0/25 (0%)		1/58 (1.7%)
Dry mouth	1/28 (3.6%)		2/25 (8%)		2/58 (3.4%)
Flatulence	1/28 (3.6%)		0/25 (0%)		1/58 (1.7%)
Nausea	2/28 (7.1%)		2/25 (8%)		2/58 (3.4%)
General disorders
Fatigue	1/28 (3.6%)		1/25 (4%)		10/58 (17.2%)
Feeling abnormal	0/28 (0%)		0/25 (0%)		2/58 (3.4%)
Feeling jittery	1/28 (3.6%)		0/25 (0%)		0/58 (0%)
Irritability	2/28 (7.1%)		2/25 (8%)		3/58 (5.2%)
Pyrexia	0/28 (0%)		1/25 (4%)		0/58 (0%)
Immune system disorders
Hypersensitivity	0/28 (0%)		1/25 (4%)		0/58 (0%)
Infections and infestations
Bronchitis	0/28 (0%)		1/25 (4%)		0/58 (0%)
Nasopharyngitis	0/28 (0%)		1/25 (4%)		0/58 (0%)
Upper respiratory tract infection	0/28 (0%)		0/25 (0%)		1/58 (1.7%)
Viral infection	0/28 (0%)		1/25 (4%)		0/58 (0%)
Injury, poisoning and procedural complications
Arthropod sting	0/28 (0%)		1/25 (4%)		0/58 (0%)
Sunburn	1/28 (3.6%)		0/25 (0%)		0/58 (0%)
Investigations
Alanine aminotransferase increased	0/28 (0%)		0/25 (0%)		1/58 (1.7%)
Aspartate aminotransferase increased	1/28 (3.6%)		0/25 (0%)		0/58 (0%)
Blood albumin increased	0/28 (0%)		1/25 (4%)		0/58 (0%)
Blood amylase increased	0/28 (0%)		1/25 (4%)		0/58 (0%)
Blood creatine phosphokinase MB increased	0/28 (0%)		1/25 (4%)		0/58 (0%)
Blood creatine phosphokinase increased	0/28 (0%)		1/25 (4%)		0/58 (0%)
Blood potassium increased	0/28 (0%)		1/25 (4%)		0/58 (0%)
Liver function test abnormal	0/28 (0%)		1/25 (4%)		2/58 (3.4%)
Metabolism and nutrition disorders
Decreased appetite	2/28 (7.1%)		1/25 (4%)		0/58 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/28 (0%)		1/25 (4%)		1/58 (1.7%)
Muscle spasms	1/28 (3.6%)		0/25 (0%)		1/58 (1.7%)
Myalgia	0/28 (0%)		1/25 (4%)		1/58 (1.7%)
Neck pain	0/28 (0%)		1/25 (4%)		1/58 (1.7%)
Tendon pain	0/28 (0%)		1/25 (4%)		1/58 (1.7%)
Nervous system disorders
Coordination abnormal	0/28 (0%)		0/25 (0%)		1/58 (1.7%)
Disturbance in attention	0/28 (0%)		1/25 (4%)		1/58 (1.7%)
Dizziness	1/28 (3.6%)		0/25 (0%)		2/58 (3.4%)
Dysgeusia	0/28 (0%)		1/25 (4%)		0/58 (0%)
Headache	5/28 (17.9%)		2/25 (8%)		10/58 (17.2%)
Memory impairment	0/28 (0%)		1/25 (4%)		1/58 (1.7%)
Migraine	0/28 (0%)		0/25 (0%)		1/58 (1.7%)
Paraesthesia	1/28 (3.6%)		1/25 (4%)		0/58 (0%)
Poor quality sleep	0/28 (0%)		1/25 (4%)		1/58 (1.7%)
Psychomotor hyperactivity	0/28 (0%)		0/25 (0%)		1/58 (1.7%)
Somnolence	2/28 (7.1%)		0/25 (0%)		1/58 (1.7%)
Tremor	0/28 (0%)		0/25 (0%)		1/58 (1.7%)
Psychiatric disorders
Abnormal dreams	2/28 (7.1%)		3/25 (12%)		3/58 (5.2%)
Anxiety	1/28 (3.6%)		0/25 (0%)		0/58 (0%)
Apathy	0/28 (0%)		0/25 (0%)		1/58 (1.7%)
Bradyphrenia	0/28 (0%)		0/25 (0%)		1/58 (1.7%)
Confusional state	0/28 (0%)		0/25 (0%)		1/58 (1.7%)
Depressed mood	0/28 (0%)		0/25 (0%)		1/58 (1.7%)
Impatience	0/28 (0%)		1/25 (4%)		0/58 (0%)
Initial insomnia	2/28 (7.1%)		2/25 (8%)		3/58 (5.2%)
Insomnia	9/28 (32.1%)		4/25 (16%)		4/58 (6.9%)
Libido decreased	1/28 (3.6%)		0/25 (0%)		1/58 (1.7%)
Middle insomnia	0/28 (0%)		1/25 (4%)		1/58 (1.7%)
Nervousness	1/28 (3.6%)		0/25 (0%)		0/58 (0%)
Sleep disorder	1/28 (3.6%)		0/25 (0%)		0/58 (0%)
Renal and urinary disorders
Urethral stenosis	1/28 (3.6%)		0/25 (0%)		0/58 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/28 (0%)		1/25 (4%)		0/58 (0%)
Epistaxis	0/28 (0%)		1/25 (4%)		0/58 (0%)
Nasal congestion	1/28 (3.6%)		0/25 (0%)		0/58 (0%)
Rhinorrhoea	0/28 (0%)		0/25 (0%)		1/58 (1.7%)
Skin and subcutaneous tissue disorders
Dermatitis contact	0/28 (0%)		0/25 (0%)		1/58 (1.7%)
Night sweats	1/28 (3.6%)		0/25 (0%)		0/58 (0%)
Pruritus	0/28 (0%)		1/25 (4%)		0/58 (0%)
Rash	1/28 (3.6%)		1/25 (4%)		0/58 (0%)
Skin lesion	1/28 (3.6%)		0/25 (0%)		0/58 (0%)
Vascular disorders
Hot flush	1/28 (3.6%)		1/25 (4%)		0/58 (0%)

Limitations/Caveats

Instead of time to sustained response, data for percentage of sustained responders in time-sensitive ADHD symptom scale (TASS) total score was reported as per planned analysis.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.