Multiple Dose Study Of BIIB118 (PF-05251749) In Healthy Volunteers

• Sponsor: Biogen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02691702
• Collaborator: (none)
• Enrollment: 97
• Locations: 2
• Arms: 3
• Actual Duration (Months): 9.5
• Patients Per Site: 48.5
• Patients Per Site Per Month: 5.1

Study Details

Study Description

Brief Summary

This is the first clinical trial to evaluate ascending multiple oral doses in healthy adult and healthy elderly subjects to characterize the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of BIIB118

Condition or Disease	Intervention/Treatment	Phase
Healthy Adult Subjects; Healthy Elderly Subjects	Drug: BIIB118; Drug: Melatonin	Phase 1

Detailed Description

This study was previously posted by Pfizer. In March, 2020, sponsorship of the trial was transferred to Biogen.

Study Design

• Study Type: Interventional
• Actual Enrollment: 97 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: A Phase 1, Double Blind, Sponsor Open, Randomized, Placebo And Active Comparator Controlled, Dose Escalation Study To Investigate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Escalating Doses Of Pf-05251749 In Healthy Adult And Elderly Subjects
• Actual Study Start Date: Mar 28, 2016
• Actual Primary Completion Date: Jan 12, 2017
• Actual Study Completion Date: Jan 12, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Multiple Doses - Part A Multiple ascending doses administered in the morning to healthy adult subjects in a parallel study design	Drug: BIIB118; Multiple ascending doses of BIIB118 (50 mg, 150 mg, 450 mg and 900 mg) as extemporaneously prepared solution/suspension administered once daily over 2 weeks; Other Names: PF-05251749 ; Drug: Melatonin; Positive control used to assess the validity of DLMO as pharmacodynamic endpoint.
Experimental: Multiple Dose - Part B Multiple ascending doses administered in the evening to healthy adult subjects in a parallel study design	Drug: BIIB118; Multiple ascending doses of BIIB118 (50 mg, 150 mg, 450 mg and 900 mg) as extemporaneously prepared solution/suspension administered once daily over 2 weeks; Other Names: PF-05251749
Experimental: Multiple Doses - Elderly Multiple ascending doses administered to elderly subjects	Drug: BIIB118; Multiple ascending doses of BIIB118 (50 mg, 150 mg, 450 mg and 900 mg) as extemporaneously prepared solution/suspension administered once daily over 2 weeks; Other Names: PF-05251749

Outcome Measures

Primary Outcome Measures

1. Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness [Baseline (0h on Day 1), Day 1 (2h), Day 4 (1.5h), Day 7 (0h, 2h), Day 10 (1.5h), Day 14 (0h, 2h), Day 15 (0h) and Day 16 (0h).]

   The Bond and Lader Visual Analogue Scales (VAS) monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items [total range 0 to 100, where each item is ordered so that higher scores indicated more alertness]), b) mood (average of 2 items [total range 0 to 100, where higher scores indicated elevated mood]), and c) calmness (average of 5 items [total range 0 to 100, where higher scores indicated more calmness]). Baseline is defined as the last available recording prior to dosing on Day 1.

2. Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness [Baseline (0h on Day 1), Day 1 (2h), Day 4 (1.5h), Day 7 (0h, 2h), Day 10 (1.5h), Day 14 (0h, 2h), Day 15 (0h) and Day 16 (0h).]

   The Bond and Lader Visual Analogue Scales (VAS) monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items [total range 0 to 100, where each item is ordered so that higher scores indicated more alertness]), b) mood (average of 2 items [total range 0 to 100, where higher scores indicated elevated mood]), and c) calmness (average of 5 items [total range 0 to 100, where higher scores indicated more calmness]). Baseline is defined as the last available recording prior to dosing on Day 1.

3. Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood [Baseline (0h on Day 1), Day 1 (2h), Day 4 (1.5h), Day 7 (0h, 2h), Day 10 (1.5h), Day 14 (0h, 2h), Day 15 (0h) and Day 16 (0h).]

   The Bond and Lader Visual Analogue Scales (VAS) monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items [total range 0 to 100, where each item is ordered so that higher scores indicated more alertness]), b) mood (average of 2 items [total range 0 to 100, where higher scores indicated elevated mood]), and c) calmness (average of 5 items [total range 0 to 100, where higher scores indicated more calmness]). Baseline is defined as the last available recording prior to dosing on Day 1.

4. Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) [Days 0, 7, 14, 16, and follow-up visit (28 calender days after the last dose of investigational product on Day 14).]

   The C-SSRS was an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced any of the following 1: completed suicide, 2: suicide attempt (response of "yes" on "actual attempt"), 3: preparatory acts toward imminent suicidal behavior ("yes" on "aborted attempt", "interrupted attempt", "preparatory acts or behavior"), 4: any suicidal behavior or ideation, suicidal ideation ("yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent"), 7: self-injurious behavior, no suicidal intent ("yes" on "has participant engaged in non-suicidal self-injurious behavior"). The new onset and worsening of post-baseline suicidality for C-SSRS was reported.

5. Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causalities) [Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).]

   An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage.

6. Number of Participants With Treatment-Emergent Adverse Events (AEs) (Treatment Related) [Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).]

   An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; The event has a causal relationship with the treatment or usage.

7. Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) [Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).]

   The laboratory test included: hematology (hemoglobin, hematocrit, red blood cell count, MCV, MCH, MCHC, platelets, white blood cell count, absolute lymphocytes, absolute total neutrophils, absolute basophils, absolute eosinophils and absolute monocytes), coagulation (PPT, prothrombin, PT international, ratio and fibrinogen, liver function(total bilirubin, direct bilirubin, aspartate, AST, Alanine, ALT, gamma GT, alkaline phosphatase, total protein and albumin), renal function (blood urea nitrogen, creatinine, HDL cholesterol, LDL cholesterol, triglycerides), Electrolytes (sodium, potassium, chloride, calcium, phosphate, venous bicarbonate), clinical chemistry (glucose, creatinine kinase), urinalysis dipstick (urine PH, urine glucose, urine ketones, urine protein, urine blood, urine urobilinogen, urine nitrite, urine leukocyte, esterase), urinalysis microscopy (urine RBC, urine WBC, urine casts, urine bacteria), miscellaneous (absolute lymphocyte marker CD4, CD8, CD19)

8. Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) [Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).]

   Number of participants with vital signs data of absolute values meeting categorical criteria was reported as following: (1) Supine systolic BP < 90 mmHg; (2) Supine Diastolic BP < 50 mmHg; (3) Supine Pulse Rate < 40 BPM ; (4) Supine Pulse Rate > 120 BPM.

9. Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) [Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).]

   Number of participants with vital signs data of increase from baseline meeting the following criteria was reported: Criterion A: maximum increase from baseline in supine systolic BP >= 30 mmHg; Criterion B: maximum increase from baseline in supine diastolic BP >= 20 mmHg. Baseline was defined as the last available recording prior to dosing.

10. Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) [Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).]

    Number of participants with vital signs data of increase from baseline meeting the following criteria was reported: Criterion A: maximum decrease from baseline in supine systolic BP >= 30 mmHg; Criterion B: maximum decrease from baseline in supine diastolic BP >= 20 mmHg. Baseline was defined as the last available recording prior to dosing.

11. Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) [Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).]

    Number of participants with ECG data of absolute values meeting categorical criteria was reported as following: Criterion A: maximum PR interval (time from the beginning of P wave to the start of QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization) >= 300 msec; Criterion B: maximum QRS complex (time from Q wave to the end of S wave, corresponding to ventricle depolarization)>= 140 msec; Criterion C: Maximum QT interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole)>= 500 msec; Criterion D: maximum QTC interval (QT interval corrected for heart rate) 450-<480 msec; Criterion E: maximum QTC interval 480-<500 msec; Criterion F: maximum QTC interval >=500 msec; Criterion G: maximum QTCF interval (QT interval corrected for heart rate using Fridericia's formula) 450 -< 480 msec; Criterion H: maximum QTCF interval 480 -< 500 msec; Criterion I: maximum QTCF interval >=500 msec.

12. Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) [Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).]

    Number of participants with ECG Data of increase from baseline meeting the following criteria was reported: Criterion A: maximum PR interval increase from baseline percentage change (PctChg)>=25/50%; Criterion B: maximum QRS complex increase from baseline PctChg >=50%; Criterion C: maximum QTC interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole, corrected for heart rate) increase from baseline 30<=change<60 msec; Criterion D: maximum QTC interval increase from baseline change >=60 msec; Criterion E: maximum QTCF (Fridericia's correction) interval increase from baseline 30<=change<60; Criterion F: maximum QTCF interval increase from baseline change >=60 msec. Baseline was defined as the average of the triplicate measurements prior to dosing on Day 1.

13. Number of Participants With New/Intensified Physical Examination Findings [Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).]

    Physical examination included examination of ears, eyes, gastrointestinal, head, heart, lungs, lymph nodes, mouth, musculoskeletal, nose, skin. The number of participants with new-intensified physical examination findings were reported.

14. Number of Participants With New/Intensified Neurological Examination Findings [Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).]

    The number of participants with new-intensified neurological examination findings were reported.

Secondary Outcome Measures

1. Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 [Days 1 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h), 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).]

   Maximum plasma concentration (Cmax) of PF-05251749 was observed directly from data on Days 1, 7 and 14.

2. Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. [Days 1 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h), 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).]

   AUCtau referred to the area under the curve from time 0 to time tau, the dosing interval, where tau equaled to 24 hours on Days 1, 7 and 14.

3. Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 [Days 1 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h), 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).]

   Tmax of PF-05251749 was observed directly from data on Days 1, 7 and 14, as time of first occurrence.

4. Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14 [Days 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).]

   Apparent clearance was influenced by the fraction of the dose absorbed, which was measured by Dose/AUCtau.

5. Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14 [Days 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).]

   Minimum concentration observed (Cmin) of PF-05251749 was observed directly from data on Days 7 and 14.

6. Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14 [Days 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).]

   Peak-to-through ratio (PTR) was the ratio of Cmax to Cmin, which was measured on Days 7 and 14.

7. Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14 [Days 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).]

   Observed accumulation ratio (Rac) was calculated as AUCtau (Days 7 or 14) divided by AUCtau (Day 1).

8. Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14 [Days 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).]

   Observed accumulation ratio for Cmax (Rac,Cmax) was calculated as: Cmax on Day 7 or 14 divided by Cmax on Day 1.

9. Terminal Half-Life (t1/2) of PF-05251749 - Day 14 [Day 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).]

   Terminal half-life (t1/2) was calculated as Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.

10. Apparent Volume of Distribution (Vz/F) of PF-05251749 - Day 14 [Day 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).]

    Apparent volume of distribution (Vz/F) was calculated by Dose/(AUCtau × kel) on Day 14.

11. Cumulative Amount of Drug Recovered Unchanged in Urine Over Dosing Interval Tau (Aetau) of PF-05251749 - Day 14 [Day 14 (0, 0.5, 1, 1.5, 2, 3, 4, 5, 8, 12, 16, 20, 24, 48h).]

    Aetau was the cumulative amount of drug recovered unchanged in urine from time 0 to end of the dosing interval, which was calculated by sum of (urine concentration × volume of urine).

12. Percentage of Dose Recovered Unchanged in Urine Over Dosing Interval Tau (Aetau%) of PF-05251749 - Day 14 [Day 14 (0, 0.5, 1, 1.5, 2, 3, 4, 5, 8, 12, 16, 20, 24, 48h).]

    Aetau% was the percentage of dose recovered unchanged into urine from 0 to end of the dosing interval, which was calculated by 100 × Aetau/Dose.

13. Renal Clearance (CLr) of PF-05251749 - Day 14 [Day 14 (0, 0.5, 1, 1.5, 2, 3, 4, 5, 8, 12, 16, 20, 24, 48h).]

    Renal clearance was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau), Aetau/AUCtau.

14. Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 6 [Day 0 (Baseline) and Day 6.]

    Dim Light Melatonin Onset (DLMO) was defined as point in time when the smooth melatonin curve exceeds the threshold. The threshold for each melatonin profile was calculated as the mean of three low consecutive daytime values (raw data points) plus twice the standard deviation of these points.

15. Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 15 [Day 0 (Baseline) and Day 15]

    DLMO was defined as point in time when the smooth melatonin curve exceeds the threshold. The threshold for each melatonin profile was calculated as the mean of three low consecutive daytime values (raw data points) plus twice the standard deviation of these points.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy male and/or female subjects of non-childbearing potential between the ages of 18 and 55 years (Parts A and B) or 65 and 85 years (Part C), inclusive (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests).

• Female subjects of non-childbearing potential must meet at least one of the following criteria:

1. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle-stimulating hormone (FSH) level confirming the post-menopausal state;

2. Have undergone a documented hysterectomy and/or bilateral oophorectomy;

3. Have medically confirmed ovarian failure. All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian failure) will be considered to be of childbearing potential.

• Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).

• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.

• Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).

• Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study medication (whichever is longer).

• Screening supine blood pressure >= 140 mm Hg (systolic) or >=90 mm Hg (diastolic), following at least 5 minutes of rest. If BP is >=140 mm Hg (systolic) or >=90 mm Hg (diastolic), repeat per local standard operating procedures (SOP). If orthostatic changes are present and deemed to be clinically significant by the investigator, Subject can be excluded.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	QPS-MRA, LLC (Miami Research Associates)	South Miami	Florida	United States	33143
2	Qps-Mra, Llc	South Miami	Florida	United States	33143

Sponsors and Collaborators

• Biogen

Investigators

• Study Director: Medical Director, Biogen

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: Biogen
• ClinicalTrials.gov Identifier: NCT02691702
• Other Study ID Numbers: B8001002; MAD
• First Posted: Feb 25, 2016
• Last Update Posted: Feb 17, 2021
• Last Verified: Feb 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Biogen: Multiple Ascending Dose Study; Safety and Tolerability; Pharmacokinetics; Pharmacodynamics; Melatonin; Plasma; Dim Light Melatonin Onset
• Additional relevant MeSH terms: Melatonin

Study Results

Participant Flow

Arm/Group Title	Placebo (Part A)	Melatonin 0.5 mg PM (Part A)	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	Placebo (Part B)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received melatonin 0.5 mg at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Period Title: Overall Study
STARTED	10	11	8	8	8	8	8	12	8	8	8
COMPLETED	8	10	7	8	8	5	5	12	6	6	6
NOT COMPLETED	2	1	1	0	0	3	3	0	2	2	2

Baseline Characteristics

Arm/Group Title	Placebo (Part A)	Melatonin 0.5 mg PM (Part A)	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	Placebo (Part B)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)	Total
Arm/Group Description	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received melatonin 0.5 mg at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Total of all reporting groups
Overall Participants	10	11	8	8	8	8	8	12	8	8	8	97
Age, Customized (participants) [Number]
< 18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
18-44 years	6 60%	7 63.6%	1 12.5%	5 62.5%	0 0%	3 37.5%	4 50%	7 58.3%	3 37.5%	6 75%	4 50%	46 47.4%
45-64 years	4 40%	4 36.4%	7 87.5%	3 37.5%	8 100%	5 62.5%	4 50%	5 41.7%	5 62.5%	2 25%	4 50%	51 52.6%
>= 65	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	1 10%	0 0%	0 0%	0 0%	5 62.5%	1 12.5%	3 37.5%	2 16.7%	1 12.5%	0 0%	2 25%	15 15.5%
Male	9 90%	11 100%	8 100%	8 100%	3 37.5%	7 87.5%	5 62.5%	10 83.3%	7 87.5%	8 100%	6 75%	82 84.5%
Race/Ethnicity, Customized (Count of Participants)
White	7 70%	9 81.8%	6 75%	8 100%	7 87.5%	7 87.5%	8 100%	10 83.3%	7 87.5%	6 75%	7 87.5%	82 84.5%
Black	3 30%	2 18.2%	2 25%	0 0%	1 12.5%	1 12.5%	0 0%	2 16.7%	1 12.5%	2 25%	1 12.5%	15 15.5%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness
Description	The Bond and Lader Visual Analogue Scales (VAS) monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items [total range 0 to 100, where each item is ordered so that higher scores indicated more alertness]), b) mood (average of 2 items [total range 0 to 100, where higher scores indicated elevated mood]), and c) calmness (average of 5 items [total range 0 to 100, where higher scores indicated more calmness]). Baseline is defined as the last available recording prior to dosing on Day 1.
Time Frame	Baseline (0h on Day 1), Day 1 (2h), Day 4 (1.5h), Day 7 (0h, 2h), Day 10 (1.5h), Day 14 (0h, 2h), Day 15 (0h) and Day 16 (0h).

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Placebo (Part A)	Melatonin 0.5 mg PM (Part A)	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	Placebo (Part B)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received melatonin 0.5 mg at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	10	11	8	8	8	8	8	12	8	8	8
Day 1 (2h)	2.16 (7.405)	7.50 (8.043)	6.71 (12.314)	3.50 (10.071)	4.58 (9.472)	4.05 (6.038)	1.49 (11.514)	-0.08 (6.382)	-2.83 (7.314)	-6.04 (10.085)	-1.93 (7.953)
Day 4 (1.5h)	-0.61 (14.480)	5.88 (8.943)	6.46 (11.092)	6.51 (11.209)	3.48 (12.533)	6.23 (8.043)	-14.45 (17.182)	-0.46 (7.105)	-0.25 (6.349)	0.65 (8.135)	-3.00 (5.143)
Day 7 (0h)	-4.00 (22.474)	3.76 (11.243)	2.21 (12.305)	6.96 (9.630)	3.39 (12.541)	6.54 (12.898)	-2.14 (9.437)	1.23 (6.356)	-0.50 (6.514)	0.23 (5.771)	-0.79 (5.109)
Day 7 (2h)	-2.87 (21.022)	-0.63 (20.162)	4.03 (14.212)	7.54 (9.519)	2.76 (6.221)	8.04 (11.784)	-10.92 (15.343)	1.57 (5.817)	-1.25 (6.743)	-3.00 (11.517)	-4.93 (9.924)
Day 10 (1.5h)	-2.97 (20.833)	4.76 (13.174)	5.83 (12.879)	6.20 (6.462)	4.83 (7.288)	7.51 (10.848)	-9.08 (21.071)	1.31 (5.667)	-0.09 (7.507)	-0.82 (7.100)	-0.53 (6.265)
Day 14 (0h)	1.19 (16.566)	4.97 (10.320)	5.68 (12.631)	1.50 (5.458)	2.96 (10.782)	8.30 (11.045)	5.12 (9.507)	1.43 (5.532)	-1.93 (9.227)	0.18 (10.212)	-0.89 (8.264)
Day 14 (2h)	-0.53 (17.945)	7.18 (11.543)	6.03 (13.385)	1.75 (14.316)	4.15 (11.839)	6.16 (11.063)	0.42 (5.971)	2.83 (5.437)	0.28 (3.998)	2.25 (5.623)	-3.33 (8.503)
Day 15 (0h)	1.55 (15.940)	7.38 (10.892)	3.51 (16.583)	9.13 (10.092)	2.13 (14.382)	8.57 (12.525)	9.20 (8.385)	1.62 (5.057)	1.07 (4.223)	3.15 (3.971)	-1.93 (6.736)
Day 16 (0h)	1.20 (17.347)	10.64 (15.791)	6.80 (15.431)	9.04 (9.736)	3.93 (11.931)	8.39 (11.696)	9.88 (8.410)	1.33 (6.533)	1.02 (3.170)	8.37 (13.401)	5.61 (6.812)

2. Primary Outcome

Title	Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness
Description	The Bond and Lader Visual Analogue Scales (VAS) monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items [total range 0 to 100, where each item is ordered so that higher scores indicated more alertness]), b) mood (average of 2 items [total range 0 to 100, where higher scores indicated elevated mood]), and c) calmness (average of 5 items [total range 0 to 100, where higher scores indicated more calmness]). Baseline is defined as the last available recording prior to dosing on Day 1.
Time Frame	Baseline (0h on Day 1), Day 1 (2h), Day 4 (1.5h), Day 7 (0h, 2h), Day 10 (1.5h), Day 14 (0h, 2h), Day 15 (0h) and Day 16 (0h).

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Placebo (Part A)	Melatonin 0.5 mg PM (Part A)	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	Placebo (Part B)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received melatonin 0.5 mg at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	10	11	8	8	8	8	8	12	8	8	8
Day 1 (2h)	0.70 (7.997)	1.45 (3.940)	3.56 (16.668)	13.88 (20.662)	1.56 (1.522)	2.25 (5.175)	1.81 (9.509)	-0.38 (2.630)	-2.06 (6.032)	-15.31 (20.114)	-0.56 (3.774)
Day 4 (1.5h)	1.00 (10.808)	4.00 (12.092)	7.50 (24.391)	16.13 (22.448)	-1.75 (8.302)	1.50 (1.732)	-11.25 (18.030)	1.25 (8.081)	-1.75 (4.652)	-5.83 (10.405)	1.19 (5.035)
Day 7 (0h)	-3.17 (20.352)	-3.85 (11.255)	8.63 (24.013)	13.44 (21.089)	1.06 (2.129)	0.50 (3.948)	-12.10 (25.289)	1.08 (7.902)	-5.19 (14.258)	-4.00 (4.950)	3.36 (10.351)
Day 7 (2h)	-2.22 (20.935)	0.40 (10.572)	7.56 (24.693)	14.44 (20.859)	1.44 (1.348)	2.14 (2.593)	-13.30 (26.537)	1.54 (8.349)	-2.31 (6.954)	-8.58 (9.881)	-1.21 (12.419)
Day 10 (1.5h)	-3.61 (19.816)	0.75 (5.149)	7.56 (24.943)	13.75 (20.707)	1.81 (1.751)	1.71 (2.464)	-11.90 (27.220)	2.46 (7.356)	-0.57 (6.194)	-5.33 (11.725)	0.21 (16.820)
Day 14 (0h)	0.88 (15.833)	2.30 (8.629)	6.88 (25.531)	14.69 (21.457)	1.94 (2.008)	-4.29 (14.502)	-10.30 (27.174)	2.88 (7.227)	-2.58 (7.902)	-4.00 (9.391)	2.86 (11.607)
Day 14 (2h)	1.75 (12.961)	2.00 (6.245)	8.06 (24.282)	15.25 (21.471)	1.44 (2.178)	2.71 (2.498)	-3.20 (8.213)	3.54 (6.600)	-1.08 (4.042)	-4.75 (9.837)	4.07 (9.467)
Day 15 (0h)	2.19 (12.764)	1.85 (8.564)	9.63 (23.242)	14.81 (21.032)	-3.25 (16.160)	2.50 (3.594)	6.80 (12.065)	2.79 (7.402)	0.17 (3.502)	0.58 (3.456)	4.86 (10.327)
Day 16 (0h)	1.81 (14.609)	0.30 (11.622)	8.94 (23.542)	16.13 (21.922)	2.00 (1.927)	2.21 (2.706)	0.90 (21.927)	2.88 (7.441)	-0.08 (2.957)	2.67 (9.548)	6.93 (11.745)

3. Primary Outcome

Title	Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood
Description	The Bond and Lader Visual Analogue Scales (VAS) monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items [total range 0 to 100, where each item is ordered so that higher scores indicated more alertness]), b) mood (average of 2 items [total range 0 to 100, where higher scores indicated elevated mood]), and c) calmness (average of 5 items [total range 0 to 100, where higher scores indicated more calmness]). Baseline is defined as the last available recording prior to dosing on Day 1.
Time Frame	Baseline (0h on Day 1), Day 1 (2h), Day 4 (1.5h), Day 7 (0h, 2h), Day 10 (1.5h), Day 14 (0h, 2h), Day 15 (0h) and Day 16 (0h).

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Placebo (Part A)	Melatonin 0.5 mg PM (Part A)	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	Placebo (Part B)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received melatonin 0.5 mg at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	10	11	8	8	8	8	8	12	8	8	8
Day 1 (2h)	1.16 (4.480)	5.16 (15.927)	2.20 (12.642)	2.03 (5.579)	5.55 (13.357)	3.25 (7.391)	0.50 (8.384)	0.32 (5.402)	-1.43 (5.432)	-7.80 (11.921)	-2.85 (10.557)
Day 4 (1.5h)	-1.42 (13.299)	2.78 (15.744)	1.85 (11.244)	2.30 (12.752)	6.84 (12.834)	5.23 (7.530)	-12.73 (13.168)	1.25 (5.218)	-3.13 (8.269)	-8.60 (12.057)	-1.73 (3.798)
Day 7 (0h)	-3.73 (17.841)	-1.86 (12.644)	0.93 (12.440)	6.20 (9.953)	7.30 (13.407)	5.83 (10.032)	-6.68 (11.595)	-0.45 (7.295)	-0.38 (4.313)	-4.90 (6.395)	-3.06 (3.878)
Day 7 (2h)	-3.00 (17.138)	3.30 (14.328)	6.65 (11.230)	3.83 (8.980)	6.30 (8.661)	5.83 (9.082)	-10.84 (11.344)	1.32 (5.811)	-2.83 (7.719)	-2.87 (3.110)	-10.00 (16.401)
Day 10 (1.5h)	-3.84 (18.444)	2.12 (16.892)	3.50 (11.745)	5.13 (8.561)	8.13 (12.784)	6.11 (8.896)	-9.92 (17.802)	1.50 (5.784)	-0.29 (4.783)	-3.97 (7.816)	-2.94 (1.672)
Day 14 (0h)	-3.65 (16.044)	4.64 (14.753)	5.13 (8.037)	2.85 (8.854)	6.33 (13.084)	3.97 (11.878)	-0.84 (7.942)	2.17 (6.178)	-2.20 (6.950)	-3.50 (8.772)	-2.09 (7.061)
Day 14 (2h)	-2.45 (19.691)	5.54 (14.101)	3.63 (12.086)	6.88 (8.256)	5.03 (14.154)	4.46 (6.410)	-2.96 (4.883)	2.10 (5.706)	-0.73 (3.259)	-2.03 (4.094)	-2.89 (6.350)
Day 15 (0h)	-1.15 (15.899)	6.52 (14.121)	4.70 (14.515)	7.13 (9.288)	3.25 (14.971)	6.51 (9.306)	2.80 (7.053)	0.78 (7.989)	-0.30 (3.067)	3.90 (10.749)	-1.26 (5.991)
Day 16 (0h)	-1.38 (17.722)	7.48 (19.847)	7.36 (12.735)	10.70 (6.978)	4.95 (15.441)	3.63 (6.738)	3.00 (5.829)	0.93 (7.767)	-0.20 (2.154)	6.60 (17.980)	1.74 (5.754)

4. Primary Outcome

Title	Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS)
Description	The C-SSRS was an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced any of the following 1: completed suicide, 2: suicide attempt (response of "yes" on "actual attempt"), 3: preparatory acts toward imminent suicidal behavior ("yes" on "aborted attempt", "interrupted attempt", "preparatory acts or behavior"), 4: any suicidal behavior or ideation, suicidal ideation ("yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent"), 7: self-injurious behavior, no suicidal intent ("yes" on "has participant engaged in non-suicidal self-injurious behavior"). The new onset and worsening of post-baseline suicidality for C-SSRS was reported.
Time Frame	Days 0, 7, 14, 16, and follow-up visit (28 calender days after the last dose of investigational product on Day 14).

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Placebo (Part A)	Melatonin 0.5 mg PM (Part A)	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	Placebo (Part B)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received melatonin 0.5 mg at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	10	11	8	8	8	8	8	12	8	8	8
Day 0	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Day 7	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Day 14	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Day 16	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Follow-up	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

5. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causalities)
Description	An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage.
Time Frame	Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Placebo (Part A)	Melatonin 0.5 mg PM (Part A)	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	Placebo (Part B)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received melatonin 0.5 mg at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	10	11	8	8	8	8	8	12	8	8	8
Number [Participants]	4 40%	3 27.3%	3 37.5%	1 12.5%	5 62.5%	7 87.5%	7 87.5%	3 25%	5 62.5%	2 25%	8 100%

6. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) (Treatment Related)
Description	An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; The event has a causal relationship with the treatment or usage.
Time Frame	Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Placebo (Part A)	Melatonin 0.5 mg PM (Part A)	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	Placebo (Part B)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received melatonin 0.5 mg at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	10	11	8	8	8	8	8	12	8	8	8
Number [Participants]	1 10%	2 18.2%	2 25%	1 12.5%	1 12.5%	5 62.5%	7 87.5%	2 16.7%	4 50%	2 25%	8 100%

7. Primary Outcome

Title	Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Description	The laboratory test included: hematology (hemoglobin, hematocrit, red blood cell count, MCV, MCH, MCHC, platelets, white blood cell count, absolute lymphocytes, absolute total neutrophils, absolute basophils, absolute eosinophils and absolute monocytes), coagulation (PPT, prothrombin, PT international, ratio and fibrinogen, liver function(total bilirubin, direct bilirubin, aspartate, AST, Alanine, ALT, gamma GT, alkaline phosphatase, total protein and albumin), renal function (blood urea nitrogen, creatinine, HDL cholesterol, LDL cholesterol, triglycerides), Electrolytes (sodium, potassium, chloride, calcium, phosphate, venous bicarbonate), clinical chemistry (glucose, creatinine kinase), urinalysis dipstick (urine PH, urine glucose, urine ketones, urine protein, urine blood, urine urobilinogen, urine nitrite, urine leukocyte, esterase), urinalysis microscopy (urine RBC, urine WBC, urine casts, urine bacteria), miscellaneous (absolute lymphocyte marker CD4, CD8, CD19)
Time Frame	Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Placebo (Part A)	Melatonin 0.5 mg PM (Part A)	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	Placebo (Part B)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received melatonin 0.5 mg at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	10	11	8	8	8	8	8	12	8	8	8
Number [Participants]	2 20%	8 72.7%	1 12.5%	2 25%	4 50%	4 50%	7 87.5%	8 66.7%	5 62.5%	5 62.5%	7 87.5%

8. Primary Outcome

Title	Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values)
Description	Number of participants with vital signs data of absolute values meeting categorical criteria was reported as following: (1) Supine systolic BP < 90 mmHg; (2) Supine Diastolic BP < 50 mmHg; (3) Supine Pulse Rate < 40 BPM ; (4) Supine Pulse Rate > 120 BPM.
Time Frame	Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Placebo (Part A)	Melatonin 0.5 mg PM (Part A)	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	Placebo (Part B)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received melatonin 0.5 mg at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	10	11	8	8	8	8	8	12	8	8	8
Supine Systolic BP < 90 mmHg	0 0%	0 0%	0 0%	0 0%	1 12.5%	1 12.5%	0 0%	0 0%	0 0%	0 0%	0 0%
Supine Diastolic BP < 50 mmHg	0 0%	0 0%	0 0%	0 0%	0 0%	1 12.5%	0 0%	0 0%	0 0%	0 0%	0 0%
Supine Pulse Rate < 40 BPM	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Supine Pulse Rate > 120 BPM	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	2 25%	0 0%	0 0%

9. Primary Outcome

Title	Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline)
Description	Number of participants with vital signs data of increase from baseline meeting the following criteria was reported: Criterion A: maximum increase from baseline in supine systolic BP >= 30 mmHg; Criterion B: maximum increase from baseline in supine diastolic BP >= 20 mmHg. Baseline was defined as the last available recording prior to dosing.
Time Frame	Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Placebo (Part A)	Melatonin 0.5 mg PM (Part A)	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	Placebo (Part B)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received melatonin 0.5 mg at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	10	11	8	8	8	8	8	12	8	8	8
Criterion A	0 0%	0 0%	1 12.5%	1 12.5%	0 0%	0 0%	0 0%	0 0%	2 25%	1 12.5%	0 0%
Criterion B	0 0%	0 0%	0 0%	2 25%	0 0%	0 0%	1 12.5%	0 0%	0 0%	0 0%	0 0%

10. Primary Outcome

Title	Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline)
Description	Number of participants with vital signs data of increase from baseline meeting the following criteria was reported: Criterion A: maximum decrease from baseline in supine systolic BP >= 30 mmHg; Criterion B: maximum decrease from baseline in supine diastolic BP >= 20 mmHg. Baseline was defined as the last available recording prior to dosing.
Time Frame	Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Placebo (Part A)	Melatonin 0.5 mg PM (Part A)	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	Placebo (Part B)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received melatonin 0.5 mg at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	10	11	8	8	8	8	8	12	8	8	8
Criterion A	2 20%	0 0%	1 12.5%	0 0%	1 12.5%	0 0%	0 0%	1 8.3%	2 25%	1 12.5%	1 12.5%
Criterion B	0 0%	0 0%	1 12.5%	0 0%	0 0%	1 12.5%	1 12.5%	1 8.3%	0 0%	0 0%	0 0%

11. Primary Outcome

Title	Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values)
Description	Number of participants with ECG data of absolute values meeting categorical criteria was reported as following: Criterion A: maximum PR interval (time from the beginning of P wave to the start of QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization) >= 300 msec; Criterion B: maximum QRS complex (time from Q wave to the end of S wave, corresponding to ventricle depolarization)>= 140 msec; Criterion C: Maximum QT interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole)>= 500 msec; Criterion D: maximum QTC interval (QT interval corrected for heart rate) 450-<480 msec; Criterion E: maximum QTC interval 480-<500 msec; Criterion F: maximum QTC interval >=500 msec; Criterion G: maximum QTCF interval (QT interval corrected for heart rate using Fridericia's formula) 450 -< 480 msec; Criterion H: maximum QTCF interval 480 -< 500 msec; Criterion I: maximum QTCF interval >=500 msec.
Time Frame	Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Placebo (Part A)	Melatonin 0.5 mg PM (Part A)	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	Placebo (Part B)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received melatonin 0.5 mg at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	10	11	8	8	8	8	8	12	8	8	8
Criterion A	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Criterion B	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Criterion C	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Criterion D	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 12.5%	0 0%	1 12.5%	0 0%	0 0%
Criterion E	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Criterion F	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Criterion G	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 12.5%	0 0%	1 12.5%	0 0%	0 0%
Criterion H	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Criterion I	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

12. Primary Outcome

Title	Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline)
Description	Number of participants with ECG Data of increase from baseline meeting the following criteria was reported: Criterion A: maximum PR interval increase from baseline percentage change (PctChg)>=25/50%; Criterion B: maximum QRS complex increase from baseline PctChg >=50%; Criterion C: maximum QTC interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole, corrected for heart rate) increase from baseline 30<=change<60 msec; Criterion D: maximum QTC interval increase from baseline change >=60 msec; Criterion E: maximum QTCF (Fridericia's correction) interval increase from baseline 30<=change<60; Criterion F: maximum QTCF interval increase from baseline change >=60 msec. Baseline was defined as the average of the triplicate measurements prior to dosing on Day 1.
Time Frame	Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Placebo (Part A)	Melatonin 0.5 mg PM (Part A)	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	Placebo (Part B)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received melatonin 0.5 mg at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	10	11	8	8	8	8	8	12	8	8	8
Criterion A	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Criterion B	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Criterion C	0 0%	0 0%	1 12.5%	0 0%	1 12.5%	0 0%	1 12.5%	2 16.7%	3 37.5%	1 12.5%	0 0%
Criterion D	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Criterion E	0 0%	0 0%	2 25%	0 0%	1 12.5%	0 0%	1 12.5%	2 16.7%	3 37.5%	1 12.5%	0 0%
Criterion F	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

13. Primary Outcome

Title	Number of Participants With New/Intensified Physical Examination Findings
Description	Physical examination included examination of ears, eyes, gastrointestinal, head, heart, lungs, lymph nodes, mouth, musculoskeletal, nose, skin. The number of participants with new-intensified physical examination findings were reported.
Time Frame	Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Placebo (Part A)	Melatonin 0.5 mg PM (Part A)	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	Placebo (Part B)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received melatonin 0.5 mg at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	10	11	8	8	8	8	8	12	8	8	8
Number [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

14. Primary Outcome

Title	Number of Participants With New/Intensified Neurological Examination Findings
Description	The number of participants with new-intensified neurological examination findings were reported.
Time Frame	Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Placebo (Part A)	Melatonin 0.5 mg PM (Part A)	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	Placebo (Part B)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received melatonin 0.5 mg at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	10	11	8	8	8	8	8	12	8	8	8
Number [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

15. Secondary Outcome

Title	Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14
Description	Maximum plasma concentration (Cmax) of PF-05251749 was observed directly from data on Days 1, 7 and 14.
Time Frame	Days 1 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h), 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic (PK) concentration population was defined as all enrolled participants treated who received at least 1 dose of PF-05251749 and had at least 1 measureable concentration.

Arm/Group Title	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	8	8	8	8	8	8	8	8
Day 1	346.1 (36)	838.1 (29)	1600 (33)	2465 (36)	3990 (17)	219.4 (23)	898.0 (23)	1833 (44)
Day 7	440.6 (23)	971.6 (26)	1583 (24)	2917 (36)	4428 (22)	239.3 (19)	1018 (29)	2747 (42)
Day 14	420.9 (42)	1068 (25)	1907 (17)	2613 (28)	4726 (19)	271.0 (22)	904.3 (55)	2714 (60)

16. Secondary Outcome

Title	Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14.
Description	AUCtau referred to the area under the curve from time 0 to time tau, the dosing interval, where tau equaled to 24 hours on Days 1, 7 and 14.
Time Frame	Days 1 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h), 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).

Outcome Measure Data

Analysis Population Description

The PK parameter population was defined as all enrolled participants treated who received at least 1 dose of PF-05251749 and had at least 1 of the PK parameters of interest measured.

Arm/Group Title	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	8	8	8	8	8	8	8	8
Day 1	1430 (39)	3302 (29)	6514 (21)	14060 (31)	26630 (25)	1626 (27)	6385 (29)	16210 (31)
Day 7	1700 (31)	4260 (20)	7662 (25)	15970 (31)	32890 (34)	1801 (21)	7018 (28)	18720 (37)
Day 14	1619 (37)	4234 (19)	8503 (24)	13640 (28)	33290 (17)	1869 (24)	6778 (35)	21950 (50)

17. Secondary Outcome

Title	Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14
Description	Tmax of PF-05251749 was observed directly from data on Days 1, 7 and 14, as time of first occurrence.
Time Frame	Days 1 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h), 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).

Outcome Measure Data

Analysis Population Description

The PK parameter population was defined as all enrolled participants treated who received at least 1 dose of PF-05251749 and had at least 1 of the PK parameters of interest measured.

Arm/Group Title	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	8	8	8	8	8	8	8	8
Day 1	1.00	1.00	1.00	1.00	1.00	1.75	1.00	1.00
Day 7	0.500	1.00	1.00	1.00	1.50	1.00	0.750	1.50
Day 14	1.00	1.00	1.00	1.00	1.00	1.00	2.00	2.00

18. Secondary Outcome

Title	Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14
Description	Apparent clearance was influenced by the fraction of the dose absorbed, which was measured by Dose/AUCtau.
Time Frame	Days 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).

Outcome Measure Data

Analysis Population Description

The PK parameter population was defined as all enrolled participants treated who received at least 1 dose of PF-05251749 and had at least 1 of the PK parameters of interest measured.

Arm/Group Title	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	8	8	8	8	8	8	8	8
Day 7	29.42 (31)	23.49 (20)	26.09 (25)	25.08 (31)	22.76 (34)	27.76 (21)	28.50 (28)	26.74 (38)
Day 14	30.86 (37)	23.61 (19)	23.53 (24)	29.34 (28)	22.51 (17)	26.76 (23)	29.54 (34)	22.82 (51)

19. Secondary Outcome

Title	Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14
Description	Minimum concentration observed (Cmin) of PF-05251749 was observed directly from data on Days 7 and 14.
Time Frame	Days 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).

Outcome Measure Data

Analysis Population Description

The PK parameter population was defined as all enrolled participants treated who received at least 1 dose of PF-05251749 and had at least 1 of the PK parameters of interest measured.

Arm/Group Title	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	8	8	8	8	8	8	8	8
Day 7	11.01 (49)	27.35 (41)	65.88 (46)	114.9 (75)	340.3 (99)	19.48 (24)	53.88 (26)	161.6 (100)
Day 14	11.40 (51)	28.89 (38)	79.56 (46)	96.98 (64)	375.7 (59)	19.11 (45)	56.77 (24)	178.6 (105)

20. Secondary Outcome

Title	Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14
Description	Peak-to-through ratio (PTR) was the ratio of Cmax to Cmin, which was measured on Days 7 and 14.
Time Frame	Days 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).

Outcome Measure Data

Analysis Population Description

The PK parameter population was defined as all enrolled participants treated who received at least 1 dose of PF-05251749 and had at least 1 of the PK parameters of interest measured.

Arm/Group Title	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	8	8	8	8	8	8	8	8
Day 7	40.04 (41)	35.54 (51)	24.01 (39)	25.37 (72)	13.00 (81)	12.29 (19)	18.90 (24)	17.02 (63)
Day 14	36.93 (18)	36.98 (33)	23.98 (35)	26.92 (65)	12.57 (64)	14.17 (49)	15.92 (34)	15.20 (101)

21. Secondary Outcome

Title	Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14
Description	Observed accumulation ratio (Rac) was calculated as AUCtau (Days 7 or 14) divided by AUCtau (Day 1).
Time Frame	Days 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).

Outcome Measure Data

Analysis Population Description

The PK parameter population was defined as all enrolled participants treated who received at least 1 dose of PF-05251749 and had at least 1 of the PK parameters of interest measured.

Arm/Group Title	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	8	8	8	8	8	8	8	8
Day 7	1.188 (16)	1.289 (13)	1.176 (9)	1.160 (17)	1.255 (7)	1.169 (12)	1.097 (7)	1.205 (14)
Day 14	1.133 (17)	1.283 (19)	1.307 (15)	0.9892 (16)	1.270 (21)	1.195 (12)	1.061 (9)	1.414 (20)

22. Secondary Outcome

Title	Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14
Description	Observed accumulation ratio for Cmax (Rac,Cmax) was calculated as: Cmax on Day 7 or 14 divided by Cmax on Day 1.
Time Frame	Days 7 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24h) and 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).

Outcome Measure Data

Analysis Population Description

The PK parameter population was defined as all enrolled participants treated who received at least 1 dose of PF-05251749 and had at least 1 of the PK parameters of interest measured.

Arm/Group Title	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	8	8	8	8	8	8	8	8
Day 7	1.272 (27)	1.160 (14)	0.9898 (21)	1.161 (34)	1.155 (10)	1.093 (12)	1.090 (28)	1.422 (52)
Day 14	1.216 (35)	1.273 (28)	1.194 (27)	1.039 (20)	1.234 (19)	1.226 (13)	0.9686 (47)	1.404 (21)

23. Secondary Outcome

Title	Terminal Half-Life (t1/2) of PF-05251749 - Day 14
Description	Terminal half-life (t1/2) was calculated as Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.
Time Frame	Day 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).

Outcome Measure Data

Analysis Population Description

The PK parameter population was defined as all enrolled participants treated who received at least 1 dose of PF-05251749 and had at least 1 of the PK parameters of interest measured.

Arm/Group Title	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	8	8	8	8	8	8	8	8
Mean (Standard Deviation) [hr]	9.625 (2.0701)	9.630 (1.6523)	10.91 (1.4405)	9.940 (2.3215)	11.20 (3.0942)	10.62 (1.4922)	8.878 (0.93101)	10.62 (2.1519)

24. Secondary Outcome

Title	Apparent Volume of Distribution (Vz/F) of PF-05251749 - Day 14
Description	Apparent volume of distribution (Vz/F) was calculated by Dose/(AUCtau × kel) on Day 14.
Time Frame	Day 14 (0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 48h).

Outcome Measure Data

Analysis Population Description

The PK parameter population was defined as all enrolled participants treated who received at least 1 dose of PF-05251749 and had at least 1 of the PK parameters of interest measured.

Arm/Group Title	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	8	8	8	8	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [L]	419.3 (39)	323.6 (27)	363.9 (21)	409.0 (43)	353.6 (17)	405.5 (14)	376.5 (42)	343.9 (36)

25. Secondary Outcome

Title	Cumulative Amount of Drug Recovered Unchanged in Urine Over Dosing Interval Tau (Aetau) of PF-05251749 - Day 14
Description	Aetau was the cumulative amount of drug recovered unchanged in urine from time 0 to end of the dosing interval, which was calculated by sum of (urine concentration × volume of urine).
Time Frame	Day 14 (0, 0.5, 1, 1.5, 2, 3, 4, 5, 8, 12, 16, 20, 24, 48h).

Outcome Measure Data

Analysis Population Description

The PK parameter population was defined as all enrolled participants treated who received at least 1 dose of PF-05251749 and had at least 1 of the PK parameters of interest measured.

Arm/Group Title	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)
Arm/Group Description	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	8	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [ng]	56710 (39)	142900 (31)	317900 (41)	404900 (59)	738300 (40)

26. Secondary Outcome

Title	Percentage of Dose Recovered Unchanged in Urine Over Dosing Interval Tau (Aetau%) of PF-05251749 - Day 14
Description	Aetau% was the percentage of dose recovered unchanged into urine from 0 to end of the dosing interval, which was calculated by 100 × Aetau/Dose.
Time Frame	Day 14 (0, 0.5, 1, 1.5, 2, 3, 4, 5, 8, 12, 16, 20, 24, 48h).

Outcome Measure Data

Analysis Population Description

The PK parameter population was defined as all enrolled participants treated who received at least 1 dose of PF-05251749 and had at least 1 of the PK parameters of interest measured.

Arm/Group Title	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)
Arm/Group Description	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	8	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Percentage of PF-05251749]	0.1133 (39)	0.1429 (31)	0.1591 (41)	0.1013 (59)	0.09849 (41)

27. Secondary Outcome

Title	Renal Clearance (CLr) of PF-05251749 - Day 14
Description	Renal clearance was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau), Aetau/AUCtau.
Time Frame	Day 14 (0, 0.5, 1, 1.5, 2, 3, 4, 5, 8, 12, 16, 20, 24, 48h).

Outcome Measure Data

Analysis Population Description

The PK parameter population was defined as all enrolled participants treated who received at least 1 dose of PF-05251749 and had at least 1 of the PK parameters of interest measured.

Arm/Group Title	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)
Arm/Group Description	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	8	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [mL/hr]	37.18 (44)	33.76 (33)	37.39 (36)	29.73 (30)	22.15 (31)

28. Secondary Outcome

Title	Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 6
Description	Dim Light Melatonin Onset (DLMO) was defined as point in time when the smooth melatonin curve exceeds the threshold. The threshold for each melatonin profile was calculated as the mean of three low consecutive daytime values (raw data points) plus twice the standard deviation of these points.
Time Frame	Day 0 (Baseline) and Day 6.

Outcome Measure Data

Analysis Population Description

The PD (pharmacodynamic) population was defined as all enrolled participants treated who provided at least 3 measurable salivary melatonin concentrations.

Arm/Group Title	Placebo (Part A)	Melatonin 0.5 mg PM (Part A)	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	Placebo (Part B)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received melatonin 0.5 mg at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	9	10	8	6	8	8	7	12	8	8	8
Mean (Standard Deviation) [min]	10.0 (45.17)	3.3 (64.42)	11.3 (45.18)	37.5 (78.90)	85.0 (83.61)	124.3 (61.06)	150.0 (56.12)	13.6 (64.85)	86.3 (84.00)	135.0 (88.49)	205.0 (44.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Part A), Melatonin 0.5 mg PM (Part A)
	Comments
	Type of Statistical Test	Other
	Comments	MMRM
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.26
	Confidence Interval	(2-Sided) 90%; -63.09 to 60.57
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 37.24
	Estimation Comments	Test (Melatonin 0.5 mg PM) Reference (Placebo)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (Part A), PF-05251749 50 mg AM (Part A)
	Comments
	Type of Statistical Test	Other
	Comments	MMRM
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-27.13
	Confidence Interval	(2-Sided) 90%; -91.24 to 36.97
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 38.61
	Estimation Comments	Test (PF-05251749 50 mg AM) Reference (Placebo)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (Part A), PF-05251749 100 mg AM (Part A)
	Comments
	Type of Statistical Test	Other
	Comments	MMRM
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	43.72
	Confidence Interval	(2-Sided) 90%; -32.19 to 119.62
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 45.72
	Estimation Comments	Test (PF-05251749 100 mg AM) Reference (Placebo)

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo (Part A), PF-05251749 200 mg AM (Part A)
	Comments
	Type of Statistical Test	Other
	Comments	MMRM
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	61.48
	Confidence Interval	(2-Sided) 90%; -6.38 to 129.35
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 40.88
	Estimation Comments	Test (PF-05251749 200 mg AM) Reference (Placebo)

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo (Part A), PF-05251749 400 mg AM (Part A)
	Comments
	Type of Statistical Test	Other
	Comments	MMRM
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	125.87
	Confidence Interval	(2-Sided) 90%; 60.51 to 191.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 39.37
	Estimation Comments	Test (PF-05251749 400 mg AM) Reference (Placebo)

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo (Part A), PF-05251749 750 mg AM (Part A)
	Comments
	Type of Statistical Test	Other
	Comments	MMRM
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	156.22
	Confidence Interval	(2-Sided) 90%; 84.99 to 227.45
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 42.91
	Estimation Comments	Test (PF-05251749 750 mg AM) Reference (Placebo)

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo (Part B), PF-05251749 50 mg PM (Part B)
	Comments
	Type of Statistical Test	Other
	Comments	MMRM
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	51.42
	Confidence Interval	(2-Sided) 90%; -3.57 to 106.41
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 33.12
	Estimation Comments	Test (PF-05251749 50 mg PM) Reference (Placebo)

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo (Part B), PF-05251749 200 mg PM (Part B)
	Comments
	Type of Statistical Test	Other
	Comments	MMRM
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	142.74
	Confidence Interval	(2-Sided) 90%; 82.76 to 202.72
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 36.13
	Estimation Comments	Test (PF-05251749 200 mg PM) Reference (Placebo)

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo (Part B), PF-05251749 500 mg PM (Part B)
	Comments
	Type of Statistical Test	Other
	Comments	MMRM
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	174.90
	Confidence Interval	(2-Sided) 90%; 115.11 to 234.69
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 36.01
	Estimation Comments	Test (PF-05251749 500 mg PM) Reference (Placebo)

29. Secondary Outcome

Title	Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 15
Description	DLMO was defined as point in time when the smooth melatonin curve exceeds the threshold. The threshold for each melatonin profile was calculated as the mean of three low consecutive daytime values (raw data points) plus twice the standard deviation of these points.
Time Frame	Day 0 (Baseline) and Day 15

Outcome Measure Data

Analysis Population Description

The PD population was defined as all enrolled participants treated who provided at least 3 measurable salivary melatonin concentrations.

Arm/Group Title	Placebo (Part A)	Melatonin 0.5 mg PM (Part A)	PF-05251749 50 mg AM (Part A)	PF-05251749 100 mg AM (Part A)	PF-05251749 200 mg AM (Part A)	PF-05251749 400 mg AM (Part A)	PF-05251749 750 mg AM (Part A)	Placebo (Part B)	PF-05251749 50 mg PM (Part B)	PF-05251749 200 mg PM (Part B)	PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received melatonin 0.5 mg at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received placebo suspensions matched to PF-05251749 at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
Measure Participants	9	10	8	6	8	8	7	12	8	8	8
Mean (Standard Deviation) [min]	40.0 (61.97)	-36.7 (93.41)	56.3 (54.23)	112.5 (75.00)	100.0 (137.70)	115.7 (118.02)	150.0 (56.12)	49.1 (103.29)	150.0 (73.48)	135.0 (88.49)	210.0 (47.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Part A), Melatonin 0.5 mg PM (Part A)
	Comments
	Type of Statistical Test	Other
	Comments	MMRM
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-71.26
	Confidence Interval	(2-Sided) 90%; -133.09 to -9.43
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 37.24
	Estimation Comments	Test (Melatonin 0.5 mg PM) Reference (Placebo)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (Part A), PF-05251749 50 mg AM (Part A)
	Comments
	Type of Statistical Test	Other
	Comments	MMRM
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-12.13
	Confidence Interval	(2-Sided) 90%; -76.24 to 51.97
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 38.61
	Estimation Comments	Test (PF-05251749 50 mg AM) Reference (Placebo)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (Part A), PF-05251749 100 mg AM (Part A)
	Comments
	Type of Statistical Test	Other
	Comments	MMRM
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	88.72
	Confidence Interval	(2-Sided) 90%; 12.81 to 164.62
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 45.72
	Estimation Comments	Test (PF-05251749 100 mg AM) Reference (Placebo)

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo (Part A), PF-05251749 200 mg AM (Part A)
	Comments
	Type of Statistical Test	Other
	Comments	MMRM
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	46.48
	Confidence Interval	(2-Sided) 90%; -21.38 to 114.35
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 40.88
	Estimation Comments	Test (PF-05251749 200 mg AM) Reference (Placebo)

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo (Part A), PF-05251749 400 mg AM (Part A)
	Comments
	Type of Statistical Test	Other
	Comments	MMRM
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	87.30
	Confidence Interval	(2-Sided) 90%; 21.94 to 152.66
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 39.37
	Estimation Comments	Test (PF-05251749 400 mg AM) Reference (Placebo)

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo (Part A), PF-05251749 750 mg AM (Part A)
	Comments
	Type of Statistical Test	Other
	Comments	MMRM
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	126.22
	Confidence Interval	(2-Sided) 90%; 54.99 to 197.45
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 42.91
	Estimation Comments	Test (PF-05251749 750 mg AM) Reference (Placebo)

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo (Part B), PF-05251749 50 mg PM (Part B)
	Comments
	Type of Statistical Test	Other
	Comments	MMRM
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	92.36
	Confidence Interval	(2-Sided) 90%; 33.51 to 151.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 35.48
	Estimation Comments	Test (PF-05251749 50 mg PM) Reference (Placebo)

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo (Part B), PF-05251749 200 mg PM (Part B)
	Comments
	Type of Statistical Test	Other
	Comments	MMRM
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	107.29
	Confidence Interval	(2-Sided) 90%; 47.31 to 167.27
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 36.13
	Estimation Comments	Test (PF-05251749 200 mg AM) Reference (Placebo)

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo (Part B), PF-05251749 500 mg PM (Part B)
	Comments
	Type of Statistical Test	Other
	Comments	MMRM
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	140.61
	Confidence Interval	(2-Sided) 90%; 77.91 to 203.30
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 37.79
	Estimation Comments	Test (PF-05251749 500 mg AM) Reference (Placebo)

Adverse Events

Time Frame	Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Arm/Group Title	Placebo (Part A)		Melatonin 0.5 mg PM (Part A)		PF-05251749 50 mg AM (Part A)		PF-05251749 100 mg AM (Part A)		PF-05251749 200 mg AM (Part A)		PF-05251749 400 mg AM (Part A)		PF-05251749 750 mg AM (Part A)		Placebo (Part B)		PF-05251749 50 mg PM (Part B)		PF-05251749 200 mg PM (Part B)		PF-05251749 500 mg PM (Part B)
Arm/Group Description	Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.		Participants received placebo suspensions matched to PF-05251749 at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received melatonin 0.5 mg at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.		Participants received PF-05251749 50 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.		Participants received PF-05251749 100 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.		Participants received PF-05251749 200 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.		Participants received PF-05251749 400 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.		Participants received PF-05251749 750 mg orally at 08:00 AM after an overnight fast on Days 1, 7, 14 (other doses were administered outside a window of ±2 hours of giving food), and also received placebo capsules matched to melatonin at 06:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.		Participants received placebo suspensions matched to PF-05251749 at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.		Participants received PF-05251749 50 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.		Participants received PF-05251749 200 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.		Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.
All Cause Mortality
	Placebo (Part A)		Melatonin 0.5 mg PM (Part A)		PF-05251749 50 mg AM (Part A)		PF-05251749 100 mg AM (Part A)		PF-05251749 200 mg AM (Part A)		PF-05251749 400 mg AM (Part A)		PF-05251749 750 mg AM (Part A)		Placebo (Part B)		PF-05251749 50 mg PM (Part B)		PF-05251749 200 mg PM (Part B)		PF-05251749 500 mg PM (Part B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Serious Adverse Events
	Placebo (Part A)		Melatonin 0.5 mg PM (Part A)		PF-05251749 50 mg AM (Part A)		PF-05251749 100 mg AM (Part A)		PF-05251749 200 mg AM (Part A)		PF-05251749 400 mg AM (Part A)		PF-05251749 750 mg AM (Part A)		Placebo (Part B)		PF-05251749 50 mg PM (Part B)		PF-05251749 200 mg PM (Part B)		PF-05251749 500 mg PM (Part B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/12 (0%)		1/8 (12.5%)		0/8 (0%)		0/8 (0%)
Cardiac disorders
Atrial fibrillation	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/12 (0%)		1/8 (12.5%)		0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Placebo (Part A)		Melatonin 0.5 mg PM (Part A)		PF-05251749 50 mg AM (Part A)		PF-05251749 100 mg AM (Part A)		PF-05251749 200 mg AM (Part A)		PF-05251749 400 mg AM (Part A)		PF-05251749 750 mg AM (Part A)		Placebo (Part B)		PF-05251749 50 mg PM (Part B)		PF-05251749 200 mg PM (Part B)		PF-05251749 500 mg PM (Part B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/10 (40%)		3/11 (27.3%)		3/8 (37.5%)		1/8 (12.5%)		5/8 (62.5%)		7/8 (87.5%)		7/8 (87.5%)		3/12 (25%)		4/8 (50%)		2/8 (25%)		8/8 (100%)
Blood and lymphatic system disorders
Thrombocytosis	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Cardiac disorders
Palpitations	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)
Gastrointestinal disorders
Constipation	1/10 (10%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)		2/8 (25%)		1/12 (8.3%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)
Diarrhoea	1/10 (10%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		2/8 (25%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Dyspepsia	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)
Frequent bowel movements	1/10 (10%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		3/8 (37.5%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Nausea	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		4/8 (50%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		2/8 (25%)
Toothache	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Vomiting	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
General disorders
Chills	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Infections and infestations
Pharyngitis	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Upper respiratory tract infection	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		2/8 (25%)		0/8 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)
Urinary tract infection	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Investigations
Alanine aminotransferase increased	0/10 (0%)		0/11 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/12 (0%)		4/8 (50%)		0/8 (0%)		0/8 (0%)
Blood creatine phosphokinase increased	1/10 (10%)		1/11 (9.1%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Electrocardiogram T wave inversion	1/10 (10%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Haemoglobin decreased	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Hepatic enzyme abnormal	0/10 (0%)		0/11 (0%)		2/8 (25%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Hepatic enzyme increased	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
White blood cell count decreased	0/10 (0%)		1/11 (9.1%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)
Nervous system disorders
Dizziness	0/10 (0%)		1/11 (9.1%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		4/8 (50%)		4/8 (50%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		4/8 (50%)
Headache	0/10 (0%)		1/11 (9.1%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		3/8 (37.5%)		1/12 (8.3%)		0/8 (0%)		2/8 (25%)		1/8 (12.5%)
Presyncope	0/10 (0%)		0/11 (0%)		1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)
Psychiatric disorders
Insomnia	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		5/8 (62.5%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		7/8 (87.5%)
Renal and urinary disorders
Haematuria	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Pruritus	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Vascular disorders
Hot flush	0/10 (0%)		0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/8 (0%)		6/8 (75%)

Limitations/Caveats

From Parts A and B, it was deemed that safety, tolerability, PK and PD objectives were met, so Part C was not conducted. Because of limited saliva sampling duration (06:00 PM to 12:00 AM), DLMO observation(s) beyond midnight could not be quantified.

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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.