Healthy Adult Subjects, Healthy Elderly Subjects
Conditions
Keywords
Multiple Ascending Dose Study, Safety and Tolerability, Pharmacokinetics, Pharmacodynamics, Melatonin, Plasma, Dim Light Melatonin Onset
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
Detailed description
This study was previously posted by Pfizer. In March, 2020, sponsorship of the trial was transferred to Biogen.
Interventions
DRUGBIIB118
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
DRUGMelatonin
Positive control used to assess the validity of DLMO as pharmacodynamic endpoint.
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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) |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo (Part A) 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. | 10 |
| Melatonin 0.5 mg PM (Part A) 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. | 11 |
| PF-05251749 50 mg AM (Part A) 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. | 8 |
| PF-05251749 100 mg AM (Part A) 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. | 8 |
| PF-05251749 200 mg AM (Part A) 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. | 8 |
| PF-05251749 400 mg AM (Part A) 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. | 8 |
| PF-05251749 750 mg AM (Part A) 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. | 8 |
| Placebo (Part B) 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. | 12 |
| PF-05251749 50 mg PM (Part B) 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. | 8 |
| PF-05251749 200 mg PM (Part B) 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. | 8 |
| PF-05251749 500 mg PM (Part B) 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. | 8 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | 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) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18-44 years | 46 participants | 6 participants | 7 participants | 1 participants | 5 participants | 0 participants | 3 participants | 4 participants | 7 participants | 3 participants | 6 participants | 4 participants |
| Age, Customized < 18 years | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Age, Customized 45-64 years | 51 participants | 4 participants | 4 participants | 7 participants | 3 participants | 8 participants | 5 participants | 4 participants | 5 participants | 5 participants | 2 participants | 4 participants |
| Age, Customized >= 65 | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Black | 15 Participants | 3 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 82 Participants | 7 Participants | 9 Participants | 6 Participants | 8 Participants | 7 Participants | 7 Participants | 8 Participants | 10 Participants | 7 Participants | 6 Participants | 7 Participants |
| Sex: Female, Male Female | 15 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 1 Participants | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 82 Participants | 9 Participants | 11 Participants | 8 Participants | 8 Participants | 3 Participants | 7 Participants | 5 Participants | 10 Participants | 7 Participants | 8 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 11 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 12 | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 4 / 10 | 3 / 11 | 3 / 8 | 1 / 8 | 5 / 8 | 7 / 8 | 7 / 8 | 3 / 12 | 4 / 8 | 2 / 8 | 8 / 8 |
| serious Total, serious adverse events | 0 / 10 | 0 / 11 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 12 | 1 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness
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).
Population: The safety analysis set included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (0h) | -4.00 Units on a scale | Standard Deviation 22.474 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (2h) | -0.53 Units on a scale | Standard Deviation 17.945 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 1 (2h) | 2.16 Units on a scale | Standard Deviation 7.405 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 15 (0h) | 1.55 Units on a scale | Standard Deviation 15.94 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (0h) | 1.19 Units on a scale | Standard Deviation 16.566 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (2h) | -2.87 Units on a scale | Standard Deviation 21.022 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 16 (0h) | 1.20 Units on a scale | Standard Deviation 17.347 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 4 (1.5h) | -0.61 Units on a scale | Standard Deviation 14.48 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 10 (1.5h) | -2.97 Units on a scale | Standard Deviation 20.833 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (2h) | -0.63 Units on a scale | Standard Deviation 20.162 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 16 (0h) | 10.64 Units on a scale | Standard Deviation 15.791 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 1 (2h) | 7.50 Units on a scale | Standard Deviation 8.043 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 4 (1.5h) | 5.88 Units on a scale | Standard Deviation 8.943 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 10 (1.5h) | 4.76 Units on a scale | Standard Deviation 13.174 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (2h) | 7.18 Units on a scale | Standard Deviation 11.543 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (0h) | 4.97 Units on a scale | Standard Deviation 10.32 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 15 (0h) | 7.38 Units on a scale | Standard Deviation 10.892 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (0h) | 3.76 Units on a scale | Standard Deviation 11.243 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (2h) | 4.03 Units on a scale | Standard Deviation 14.212 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 10 (1.5h) | 5.83 Units on a scale | Standard Deviation 12.879 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (2h) | 6.03 Units on a scale | Standard Deviation 13.385 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 4 (1.5h) | 6.46 Units on a scale | Standard Deviation 11.092 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 16 (0h) | 6.80 Units on a scale | Standard Deviation 15.431 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (0h) | 2.21 Units on a scale | Standard Deviation 12.305 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (0h) | 5.68 Units on a scale | Standard Deviation 12.631 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 1 (2h) | 6.71 Units on a scale | Standard Deviation 12.314 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 15 (0h) | 3.51 Units on a scale | Standard Deviation 16.583 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 4 (1.5h) | 6.51 Units on a scale | Standard Deviation 11.209 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (0h) | 6.96 Units on a scale | Standard Deviation 9.63 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 15 (0h) | 9.13 Units on a scale | Standard Deviation 10.092 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (0h) | 1.50 Units on a scale | Standard Deviation 5.458 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 10 (1.5h) | 6.20 Units on a scale | Standard Deviation 6.462 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (2h) | 1.75 Units on a scale | Standard Deviation 14.316 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 1 (2h) | 3.50 Units on a scale | Standard Deviation 10.071 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (2h) | 7.54 Units on a scale | Standard Deviation 9.519 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 16 (0h) | 9.04 Units on a scale | Standard Deviation 9.736 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 15 (0h) | 2.13 Units on a scale | Standard Deviation 14.382 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (2h) | 2.76 Units on a scale | Standard Deviation 6.221 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 4 (1.5h) | 3.48 Units on a scale | Standard Deviation 12.533 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (0h) | 3.39 Units on a scale | Standard Deviation 12.541 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (2h) | 4.15 Units on a scale | Standard Deviation 11.839 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (0h) | 2.96 Units on a scale | Standard Deviation 10.782 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 1 (2h) | 4.58 Units on a scale | Standard Deviation 9.472 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 10 (1.5h) | 4.83 Units on a scale | Standard Deviation 7.288 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 16 (0h) | 3.93 Units on a scale | Standard Deviation 11.931 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (0h) | 8.30 Units on a scale | Standard Deviation 11.045 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 1 (2h) | 4.05 Units on a scale | Standard Deviation 6.038 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 10 (1.5h) | 7.51 Units on a scale | Standard Deviation 10.848 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 4 (1.5h) | 6.23 Units on a scale | Standard Deviation 8.043 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (0h) | 6.54 Units on a scale | Standard Deviation 12.898 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (2h) | 8.04 Units on a scale | Standard Deviation 11.784 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 16 (0h) | 8.39 Units on a scale | Standard Deviation 11.696 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 15 (0h) | 8.57 Units on a scale | Standard Deviation 12.525 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (2h) | 6.16 Units on a scale | Standard Deviation 11.063 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 10 (1.5h) | -9.08 Units on a scale | Standard Deviation 21.071 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (2h) | -10.92 Units on a scale | Standard Deviation 15.343 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 16 (0h) | 9.88 Units on a scale | Standard Deviation 8.41 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (0h) | -2.14 Units on a scale | Standard Deviation 9.437 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (2h) | 0.42 Units on a scale | Standard Deviation 5.971 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (0h) | 5.12 Units on a scale | Standard Deviation 9.507 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 4 (1.5h) | -14.45 Units on a scale | Standard Deviation 17.182 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 1 (2h) | 1.49 Units on a scale | Standard Deviation 11.514 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 15 (0h) | 9.20 Units on a scale | Standard Deviation 8.385 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 1 (2h) | -0.08 Units on a scale | Standard Deviation 6.382 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 15 (0h) | 1.62 Units on a scale | Standard Deviation 5.057 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (2h) | 2.83 Units on a scale | Standard Deviation 5.437 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (2h) | 1.57 Units on a scale | Standard Deviation 5.817 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (0h) | 1.43 Units on a scale | Standard Deviation 5.532 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 16 (0h) | 1.33 Units on a scale | Standard Deviation 6.533 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (0h) | 1.23 Units on a scale | Standard Deviation 6.356 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 4 (1.5h) | -0.46 Units on a scale | Standard Deviation 7.105 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 10 (1.5h) | 1.31 Units on a scale | Standard Deviation 5.667 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 15 (0h) | 1.07 Units on a scale | Standard Deviation 4.223 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 1 (2h) | -2.83 Units on a scale | Standard Deviation 7.314 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 4 (1.5h) | -0.25 Units on a scale | Standard Deviation 6.349 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (0h) | -0.50 Units on a scale | Standard Deviation 6.514 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (2h) | -1.25 Units on a scale | Standard Deviation 6.743 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 10 (1.5h) | -0.09 Units on a scale | Standard Deviation 7.507 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (0h) | -1.93 Units on a scale | Standard Deviation 9.227 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (2h) | 0.28 Units on a scale | Standard Deviation 3.998 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 16 (0h) | 1.02 Units on a scale | Standard Deviation 3.17 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (2h) | 2.25 Units on a scale | Standard Deviation 5.623 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 10 (1.5h) | -0.82 Units on a scale | Standard Deviation 7.1 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (2h) | -3.00 Units on a scale | Standard Deviation 11.517 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (0h) | 0.23 Units on a scale | Standard Deviation 5.771 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 4 (1.5h) | 0.65 Units on a scale | Standard Deviation 8.135 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 1 (2h) | -6.04 Units on a scale | Standard Deviation 10.085 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 15 (0h) | 3.15 Units on a scale | Standard Deviation 3.971 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (0h) | 0.18 Units on a scale | Standard Deviation 10.212 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 16 (0h) | 8.37 Units on a scale | Standard Deviation 13.401 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (2h) | -3.33 Units on a scale | Standard Deviation 8.503 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 14 (0h) | -0.89 Units on a scale | Standard Deviation 8.264 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 1 (2h) | -1.93 Units on a scale | Standard Deviation 7.953 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (2h) | -4.93 Units on a scale | Standard Deviation 9.924 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 10 (1.5h) | -0.53 Units on a scale | Standard Deviation 6.265 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 7 (0h) | -0.79 Units on a scale | Standard Deviation 5.109 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 15 (0h) | -1.93 Units on a scale | Standard Deviation 6.736 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 16 (0h) | 5.61 Units on a scale | Standard Deviation 6.812 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Alertness | Day 4 (1.5h) | -3.00 Units on a scale | Standard Deviation 5.143 |
Primary
Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness
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).
Population: The safety analysis set included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 10 (1.5h) | -3.61 Units on a scale | Standard Deviation 19.816 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 15 (0h) | 2.19 Units on a scale | Standard Deviation 12.764 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (2h) | 1.75 Units on a scale | Standard Deviation 12.961 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 16 (0h) | 1.81 Units on a scale | Standard Deviation 14.609 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 4 (1.5h) | 1.00 Units on a scale | Standard Deviation 10.808 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (2h) | -2.22 Units on a scale | Standard Deviation 20.935 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (0h) | -3.17 Units on a scale | Standard Deviation 20.352 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (0h) | 0.88 Units on a scale | Standard Deviation 15.833 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 1 (2h) | 0.70 Units on a scale | Standard Deviation 7.997 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (0h) | 2.30 Units on a scale | Standard Deviation 8.629 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (2h) | 2.00 Units on a scale | Standard Deviation 6.245 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 10 (1.5h) | 0.75 Units on a scale | Standard Deviation 5.149 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 1 (2h) | 1.45 Units on a scale | Standard Deviation 3.94 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (2h) | 0.40 Units on a scale | Standard Deviation 10.572 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 15 (0h) | 1.85 Units on a scale | Standard Deviation 8.564 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (0h) | -3.85 Units on a scale | Standard Deviation 11.255 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 16 (0h) | 0.30 Units on a scale | Standard Deviation 11.622 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 4 (1.5h) | 4.00 Units on a scale | Standard Deviation 12.092 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (0h) | 6.88 Units on a scale | Standard Deviation 25.531 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 10 (1.5h) | 7.56 Units on a scale | Standard Deviation 24.943 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 4 (1.5h) | 7.50 Units on a scale | Standard Deviation 24.391 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (2h) | 8.06 Units on a scale | Standard Deviation 24.282 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 16 (0h) | 8.94 Units on a scale | Standard Deviation 23.542 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 1 (2h) | 3.56 Units on a scale | Standard Deviation 16.668 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (2h) | 7.56 Units on a scale | Standard Deviation 24.693 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 15 (0h) | 9.63 Units on a scale | Standard Deviation 23.242 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (0h) | 8.63 Units on a scale | Standard Deviation 24.013 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (2h) | 14.44 Units on a scale | Standard Deviation 20.859 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (0h) | 14.69 Units on a scale | Standard Deviation 21.457 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (0h) | 13.44 Units on a scale | Standard Deviation 21.089 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 15 (0h) | 14.81 Units on a scale | Standard Deviation 21.032 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (2h) | 15.25 Units on a scale | Standard Deviation 21.471 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 4 (1.5h) | 16.13 Units on a scale | Standard Deviation 22.448 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 10 (1.5h) | 13.75 Units on a scale | Standard Deviation 20.707 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 1 (2h) | 13.88 Units on a scale | Standard Deviation 20.662 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 16 (0h) | 16.13 Units on a scale | Standard Deviation 21.922 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 1 (2h) | 1.56 Units on a scale | Standard Deviation 1.522 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (0h) | 1.94 Units on a scale | Standard Deviation 2.008 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 16 (0h) | 2.00 Units on a scale | Standard Deviation 1.927 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 4 (1.5h) | -1.75 Units on a scale | Standard Deviation 8.302 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 15 (0h) | -3.25 Units on a scale | Standard Deviation 16.16 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (0h) | 1.06 Units on a scale | Standard Deviation 2.129 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (2h) | 1.44 Units on a scale | Standard Deviation 2.178 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (2h) | 1.44 Units on a scale | Standard Deviation 1.348 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 10 (1.5h) | 1.81 Units on a scale | Standard Deviation 1.751 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 16 (0h) | 2.21 Units on a scale | Standard Deviation 2.706 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (2h) | 2.14 Units on a scale | Standard Deviation 2.593 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 15 (0h) | 2.50 Units on a scale | Standard Deviation 3.594 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 4 (1.5h) | 1.50 Units on a scale | Standard Deviation 1.732 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 1 (2h) | 2.25 Units on a scale | Standard Deviation 5.175 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 10 (1.5h) | 1.71 Units on a scale | Standard Deviation 2.464 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (0h) | -4.29 Units on a scale | Standard Deviation 14.502 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (2h) | 2.71 Units on a scale | Standard Deviation 2.498 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (0h) | 0.50 Units on a scale | Standard Deviation 3.948 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (0h) | -12.10 Units on a scale | Standard Deviation 25.289 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (0h) | -10.30 Units on a scale | Standard Deviation 27.174 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 4 (1.5h) | -11.25 Units on a scale | Standard Deviation 18.03 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 1 (2h) | 1.81 Units on a scale | Standard Deviation 9.509 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (2h) | -13.30 Units on a scale | Standard Deviation 26.537 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 10 (1.5h) | -11.90 Units on a scale | Standard Deviation 27.22 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (2h) | -3.20 Units on a scale | Standard Deviation 8.213 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 15 (0h) | 6.80 Units on a scale | Standard Deviation 12.065 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 16 (0h) | 0.90 Units on a scale | Standard Deviation 21.927 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (0h) | 2.88 Units on a scale | Standard Deviation 7.227 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 10 (1.5h) | 2.46 Units on a scale | Standard Deviation 7.356 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (2h) | 3.54 Units on a scale | Standard Deviation 6.6 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 16 (0h) | 2.88 Units on a scale | Standard Deviation 7.441 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (0h) | 1.08 Units on a scale | Standard Deviation 7.902 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 1 (2h) | -0.38 Units on a scale | Standard Deviation 2.63 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (2h) | 1.54 Units on a scale | Standard Deviation 8.349 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 15 (0h) | 2.79 Units on a scale | Standard Deviation 7.402 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 4 (1.5h) | 1.25 Units on a scale | Standard Deviation 8.081 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 10 (1.5h) | -0.57 Units on a scale | Standard Deviation 6.194 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (0h) | -2.58 Units on a scale | Standard Deviation 7.902 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (0h) | -5.19 Units on a scale | Standard Deviation 14.258 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 16 (0h) | -0.08 Units on a scale | Standard Deviation 2.957 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (2h) | -1.08 Units on a scale | Standard Deviation 4.042 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 4 (1.5h) | -1.75 Units on a scale | Standard Deviation 4.652 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 15 (0h) | 0.17 Units on a scale | Standard Deviation 3.502 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 1 (2h) | -2.06 Units on a scale | Standard Deviation 6.032 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (2h) | -2.31 Units on a scale | Standard Deviation 6.954 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 4 (1.5h) | -5.83 Units on a scale | Standard Deviation 10.405 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (0h) | -4.00 Units on a scale | Standard Deviation 4.95 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 16 (0h) | 2.67 Units on a scale | Standard Deviation 9.548 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 15 (0h) | 0.58 Units on a scale | Standard Deviation 3.456 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 1 (2h) | -15.31 Units on a scale | Standard Deviation 20.114 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 10 (1.5h) | -5.33 Units on a scale | Standard Deviation 11.725 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (2h) | -8.58 Units on a scale | Standard Deviation 9.881 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (0h) | -4.00 Units on a scale | Standard Deviation 9.391 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (2h) | -4.75 Units on a scale | Standard Deviation 9.837 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (2h) | 4.07 Units on a scale | Standard Deviation 9.467 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 14 (0h) | 2.86 Units on a scale | Standard Deviation 11.607 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (2h) | -1.21 Units on a scale | Standard Deviation 12.419 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 7 (0h) | 3.36 Units on a scale | Standard Deviation 10.351 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 10 (1.5h) | 0.21 Units on a scale | Standard Deviation 16.82 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 4 (1.5h) | 1.19 Units on a scale | Standard Deviation 5.035 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 15 (0h) | 4.86 Units on a scale | Standard Deviation 10.327 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 1 (2h) | -0.56 Units on a scale | Standard Deviation 3.774 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16 - Calmness | Day 16 (0h) | 6.93 Units on a scale | Standard Deviation 11.745 |
Primary
Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood
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).
Population: The safety analysis set included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (0h) | -3.65 Units on a scale | Standard Deviation 16.044 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 1 (2h) | 1.16 Units on a scale | Standard Deviation 4.48 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 4 (1.5h) | -1.42 Units on a scale | Standard Deviation 13.299 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (2h) | -2.45 Units on a scale | Standard Deviation 19.691 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 15 (0h) | -1.15 Units on a scale | Standard Deviation 15.899 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 10 (1.5h) | -3.84 Units on a scale | Standard Deviation 18.444 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (2h) | -3.00 Units on a scale | Standard Deviation 17.138 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 16 (0h) | -1.38 Units on a scale | Standard Deviation 17.722 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (0h) | -3.73 Units on a scale | Standard Deviation 17.841 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 1 (2h) | 5.16 Units on a scale | Standard Deviation 15.927 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (2h) | 3.30 Units on a scale | Standard Deviation 14.328 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 16 (0h) | 7.48 Units on a scale | Standard Deviation 19.847 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (2h) | 5.54 Units on a scale | Standard Deviation 14.101 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 4 (1.5h) | 2.78 Units on a scale | Standard Deviation 15.744 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (0h) | 4.64 Units on a scale | Standard Deviation 14.753 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 15 (0h) | 6.52 Units on a scale | Standard Deviation 14.121 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (0h) | -1.86 Units on a scale | Standard Deviation 12.644 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 10 (1.5h) | 2.12 Units on a scale | Standard Deviation 16.892 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 15 (0h) | 4.70 Units on a scale | Standard Deviation 14.515 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (0h) | 5.13 Units on a scale | Standard Deviation 8.037 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 10 (1.5h) | 3.50 Units on a scale | Standard Deviation 11.745 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (2h) | 3.63 Units on a scale | Standard Deviation 12.086 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (2h) | 6.65 Units on a scale | Standard Deviation 11.23 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 1 (2h) | 2.20 Units on a scale | Standard Deviation 12.642 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (0h) | 0.93 Units on a scale | Standard Deviation 12.44 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 16 (0h) | 7.36 Units on a scale | Standard Deviation 12.735 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 4 (1.5h) | 1.85 Units on a scale | Standard Deviation 11.244 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 10 (1.5h) | 5.13 Units on a scale | Standard Deviation 8.561 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (0h) | 2.85 Units on a scale | Standard Deviation 8.854 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (0h) | 6.20 Units on a scale | Standard Deviation 9.953 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 4 (1.5h) | 2.30 Units on a scale | Standard Deviation 12.752 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 15 (0h) | 7.13 Units on a scale | Standard Deviation 9.288 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 1 (2h) | 2.03 Units on a scale | Standard Deviation 5.579 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 16 (0h) | 10.70 Units on a scale | Standard Deviation 6.978 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (2h) | 6.88 Units on a scale | Standard Deviation 8.256 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (2h) | 3.83 Units on a scale | Standard Deviation 8.98 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 10 (1.5h) | 8.13 Units on a scale | Standard Deviation 12.784 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 4 (1.5h) | 6.84 Units on a scale | Standard Deviation 12.834 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 15 (0h) | 3.25 Units on a scale | Standard Deviation 14.971 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (0h) | 7.30 Units on a scale | Standard Deviation 13.407 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (2h) | 6.30 Units on a scale | Standard Deviation 8.661 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 16 (0h) | 4.95 Units on a scale | Standard Deviation 15.441 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (0h) | 6.33 Units on a scale | Standard Deviation 13.084 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (2h) | 5.03 Units on a scale | Standard Deviation 14.154 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 1 (2h) | 5.55 Units on a scale | Standard Deviation 13.357 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 1 (2h) | 3.25 Units on a scale | Standard Deviation 7.391 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (0h) | 3.97 Units on a scale | Standard Deviation 11.878 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 4 (1.5h) | 5.23 Units on a scale | Standard Deviation 7.53 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 15 (0h) | 6.51 Units on a scale | Standard Deviation 9.306 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 16 (0h) | 3.63 Units on a scale | Standard Deviation 6.738 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (0h) | 5.83 Units on a scale | Standard Deviation 10.032 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 10 (1.5h) | 6.11 Units on a scale | Standard Deviation 8.896 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (2h) | 5.83 Units on a scale | Standard Deviation 9.082 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (2h) | 4.46 Units on a scale | Standard Deviation 6.41 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 16 (0h) | 3.00 Units on a scale | Standard Deviation 5.829 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (0h) | -6.68 Units on a scale | Standard Deviation 11.595 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 10 (1.5h) | -9.92 Units on a scale | Standard Deviation 17.802 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 4 (1.5h) | -12.73 Units on a scale | Standard Deviation 13.168 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (0h) | -0.84 Units on a scale | Standard Deviation 7.942 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 1 (2h) | 0.50 Units on a scale | Standard Deviation 8.384 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 15 (0h) | 2.80 Units on a scale | Standard Deviation 7.053 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (2h) | -2.96 Units on a scale | Standard Deviation 4.883 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (2h) | -10.84 Units on a scale | Standard Deviation 11.344 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 16 (0h) | 0.93 Units on a scale | Standard Deviation 7.767 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (0h) | 2.17 Units on a scale | Standard Deviation 6.178 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 1 (2h) | 0.32 Units on a scale | Standard Deviation 5.402 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 10 (1.5h) | 1.50 Units on a scale | Standard Deviation 5.784 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (2h) | 1.32 Units on a scale | Standard Deviation 5.811 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (2h) | 2.10 Units on a scale | Standard Deviation 5.706 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 4 (1.5h) | 1.25 Units on a scale | Standard Deviation 5.218 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 15 (0h) | 0.78 Units on a scale | Standard Deviation 7.989 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (0h) | -0.45 Units on a scale | Standard Deviation 7.295 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 4 (1.5h) | -3.13 Units on a scale | Standard Deviation 8.269 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 15 (0h) | -0.30 Units on a scale | Standard Deviation 3.067 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (0h) | -2.20 Units on a scale | Standard Deviation 6.95 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 16 (0h) | -0.20 Units on a scale | Standard Deviation 2.154 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 1 (2h) | -1.43 Units on a scale | Standard Deviation 5.432 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (2h) | -0.73 Units on a scale | Standard Deviation 3.259 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (0h) | -0.38 Units on a scale | Standard Deviation 4.313 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 10 (1.5h) | -0.29 Units on a scale | Standard Deviation 4.783 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (2h) | -2.83 Units on a scale | Standard Deviation 7.719 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 15 (0h) | 3.90 Units on a scale | Standard Deviation 10.749 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 1 (2h) | -7.80 Units on a scale | Standard Deviation 11.921 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 4 (1.5h) | -8.60 Units on a scale | Standard Deviation 12.057 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (0h) | -4.90 Units on a scale | Standard Deviation 6.395 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (2h) | -2.87 Units on a scale | Standard Deviation 3.11 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 10 (1.5h) | -3.97 Units on a scale | Standard Deviation 7.816 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (0h) | -3.50 Units on a scale | Standard Deviation 8.772 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (2h) | -2.03 Units on a scale | Standard Deviation 4.094 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 16 (0h) | 6.60 Units on a scale | Standard Deviation 17.98 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (2h) | -2.89 Units on a scale | Standard Deviation 6.35 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 14 (0h) | -2.09 Units on a scale | Standard Deviation 7.061 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 10 (1.5h) | -2.94 Units on a scale | Standard Deviation 1.672 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (2h) | -10.00 Units on a scale | Standard Deviation 16.401 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 7 (0h) | -3.06 Units on a scale | Standard Deviation 3.878 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 4 (1.5h) | -1.73 Units on a scale | Standard Deviation 3.798 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 1 (2h) | -2.85 Units on a scale | Standard Deviation 10.557 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 16 (0h) | 1.74 Units on a scale | Standard Deviation 5.754 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (BL-VAS) on Days 1, 4, 7, 10, 14, 15 and 16- Mood | Day 15 (0h) | -1.26 Units on a scale | Standard Deviation 5.991 |
Primary
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values)
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).
Population: The safety analysis set included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion E | 0 Participants |
| Placebo (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion G | 0 Participants |
| Placebo (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion C | 0 Participants |
| Placebo (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion D | 0 Participants |
| Placebo (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion A | 0 Participants |
| Placebo (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion I | 0 Participants |
| Placebo (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion H | 0 Participants |
| Placebo (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion B | 0 Participants |
| Placebo (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion F | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion B | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion C | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion H | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion E | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion A | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion G | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion D | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion I | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion F | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion F | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion I | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion A | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion B | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion H | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion C | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion D | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion G | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion E | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion B | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion C | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion G | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion E | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion D | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion A | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion I | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion F | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion H | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion H | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion D | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion F | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion C | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion A | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion B | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion I | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion E | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion G | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion B | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion A | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion I | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion D | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion F | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion E | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion C | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion H | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion G | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion A | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion B | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion C | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion D | 1 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion E | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion F | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion G | 1 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion H | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion I | 0 Participants |
| Placebo (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion I | 0 Participants |
| Placebo (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion F | 0 Participants |
| Placebo (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion D | 0 Participants |
| Placebo (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion G | 0 Participants |
| Placebo (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion C | 0 Participants |
| Placebo (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion B | 0 Participants |
| Placebo (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion H | 0 Participants |
| Placebo (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion A | 0 Participants |
| Placebo (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion E | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion C | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion I | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion G | 1 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion B | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion H | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion A | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion E | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion F | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion D | 1 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion G | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion F | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion A | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion D | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion H | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion I | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion C | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion B | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion E | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion F | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion A | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion H | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion D | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion C | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion G | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion I | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion B | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) | Criterion E | 0 Participants |
Primary
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline)
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).
Population: The safety analysis set included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion E | 0 Participants |
| Placebo (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion A | 0 Participants |
| Placebo (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion B | 0 Participants |
| Placebo (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion F | 0 Participants |
| Placebo (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion D | 0 Participants |
| Placebo (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion C | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion B | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion E | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion F | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion D | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion C | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion A | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion C | 1 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion E | 2 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion A | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion D | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion B | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion F | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion C | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion E | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion D | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion F | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion B | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion A | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion E | 1 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion A | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion B | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion C | 1 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion D | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion F | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion D | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion B | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion C | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion A | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion E | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion F | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion C | 1 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion E | 1 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion B | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion D | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion A | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion F | 0 Participants |
| Placebo (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion A | 0 Participants |
| Placebo (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion F | 0 Participants |
| Placebo (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion C | 2 Participants |
| Placebo (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion B | 0 Participants |
| Placebo (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion D | 0 Participants |
| Placebo (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion E | 2 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion F | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion C | 3 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion D | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion E | 3 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion A | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion B | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion C | 1 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion A | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion F | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion D | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion B | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion E | 1 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion B | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion E | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion C | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion F | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion A | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) | Criterion D | 0 Participants |
Primary
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
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).
Population: The safety analysis set included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | 2 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | 8 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | 1 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | 2 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | 4 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | 4 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | 7 Participants |
| Placebo (Part B) | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | 8 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | 5 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | 5 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | 7 Participants |
Primary
Number of Participants With New/Intensified Neurological Examination Findings
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).
Population: The safety analysis set included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Number of Participants With New/Intensified Neurological Examination Findings | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With New/Intensified Neurological Examination Findings | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With New/Intensified Neurological Examination Findings | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With New/Intensified Neurological Examination Findings | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With New/Intensified Neurological Examination Findings | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With New/Intensified Neurological Examination Findings | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With New/Intensified Neurological Examination Findings | 0 Participants |
| Placebo (Part B) | Number of Participants With New/Intensified Neurological Examination Findings | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With New/Intensified Neurological Examination Findings | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With New/Intensified Neurological Examination Findings | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With New/Intensified Neurological Examination Findings | 0 Participants |
Primary
Number of Participants With New/Intensified Physical Examination Findings
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).
Population: The safety analysis set included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Number of Participants With New/Intensified Physical Examination Findings | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With New/Intensified Physical Examination Findings | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With New/Intensified Physical Examination Findings | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With New/Intensified Physical Examination Findings | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With New/Intensified Physical Examination Findings | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With New/Intensified Physical Examination Findings | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With New/Intensified Physical Examination Findings | 0 Participants |
| Placebo (Part B) | Number of Participants With New/Intensified Physical Examination Findings | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With New/Intensified Physical Examination Findings | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With New/Intensified Physical Examination Findings | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With New/Intensified Physical Examination Findings | 0 Participants |
Primary
Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS)
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).
Population: The safety analysis set included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 16 | 0 Participants |
| Placebo (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 0 | 0 Participants |
| Placebo (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 14 | 0 Participants |
| Placebo (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Follow-up | 0 Participants |
| Placebo (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 7 | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 7 | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 14 | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Follow-up | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 16 | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 0 | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 14 | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Follow-up | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 0 | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 16 | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 7 | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Follow-up | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 0 | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 7 | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 16 | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 14 | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 7 | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Follow-up | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 0 | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 16 | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 14 | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 7 | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 0 | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 14 | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 16 | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Follow-up | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Follow-up | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 0 | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 16 | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 14 | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 7 | 0 Participants |
| Placebo (Part B) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 7 | 0 Participants |
| Placebo (Part B) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Follow-up | 0 Participants |
| Placebo (Part B) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 14 | 0 Participants |
| Placebo (Part B) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 0 | 0 Participants |
| Placebo (Part B) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 16 | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 14 | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Follow-up | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 0 | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 7 | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 16 | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 7 | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 14 | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 16 | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Follow-up | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 0 | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 0 | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 16 | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Follow-up | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 7 | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) | Day 14 | 0 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causalities)
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).
Population: The safety analysis set included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causalities) | 4 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causalities) | 3 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causalities) | 3 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causalities) | 1 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causalities) | 5 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causalities) | 7 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causalities) | 7 Participants |
| Placebo (Part B) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causalities) | 3 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causalities) | 5 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causalities) | 2 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causalities) | 8 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (AEs) (Treatment Related)
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).
Population: The safety analysis set included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (Treatment Related) | 1 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (Treatment Related) | 2 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (Treatment Related) | 2 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (Treatment Related) | 1 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (Treatment Related) | 1 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (Treatment Related) | 5 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (Treatment Related) | 7 Participants |
| Placebo (Part B) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (Treatment Related) | 2 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (Treatment Related) | 4 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (Treatment Related) | 2 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Treatment-Emergent Adverse Events (AEs) (Treatment Related) | 8 Participants |
Primary
Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values)
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).
Population: The safety analysis set included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Diastolic BP < 50 mmHg | 0 Participants |
| Placebo (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate < 40 BPM | 0 Participants |
| Placebo (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Systolic BP < 90 mmHg | 0 Participants |
| Placebo (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate > 120 BPM | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Diastolic BP < 50 mmHg | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Systolic BP < 90 mmHg | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate < 40 BPM | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate > 120 BPM | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate < 40 BPM | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Systolic BP < 90 mmHg | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Diastolic BP < 50 mmHg | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate > 120 BPM | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate < 40 BPM | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate > 120 BPM | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Systolic BP < 90 mmHg | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Diastolic BP < 50 mmHg | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate < 40 BPM | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Systolic BP < 90 mmHg | 1 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate > 120 BPM | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Diastolic BP < 50 mmHg | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate < 40 BPM | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate > 120 BPM | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Systolic BP < 90 mmHg | 1 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Diastolic BP < 50 mmHg | 1 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate < 40 BPM | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Diastolic BP < 50 mmHg | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate > 120 BPM | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Systolic BP < 90 mmHg | 0 Participants |
| Placebo (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Systolic BP < 90 mmHg | 0 Participants |
| Placebo (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Diastolic BP < 50 mmHg | 0 Participants |
| Placebo (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate < 40 BPM | 0 Participants |
| Placebo (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate > 120 BPM | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate < 40 BPM | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Systolic BP < 90 mmHg | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Diastolic BP < 50 mmHg | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate > 120 BPM | 2 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Systolic BP < 90 mmHg | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate < 40 BPM | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate > 120 BPM | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Diastolic BP < 50 mmHg | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate > 120 BPM | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Systolic BP < 90 mmHg | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Pulse Rate < 40 BPM | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) | Supine Diastolic BP < 50 mmHg | 0 Participants |
Primary
Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline)
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).
Population: The safety analysis set included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion B | 0 Participants |
| Placebo (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion A | 2 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion B | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion A | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion A | 1 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion B | 1 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion B | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion A | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion A | 1 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion B | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion A | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion B | 1 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion B | 1 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion A | 0 Participants |
| Placebo (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion B | 1 Participants |
| Placebo (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion A | 1 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion A | 2 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion B | 0 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion A | 1 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion B | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion A | 1 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) | Criterion B | 0 Participants |
Primary
Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline)
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).
Population: The safety analysis set included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion A | 0 Participants |
| Placebo (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion B | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion A | 0 Participants |
| Melatonin 0.5 mg PM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion B | 0 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion A | 1 Participants |
| PF-05251749 50 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion B | 0 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion A | 1 Participants |
| PF-05251749 100 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion B | 2 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion A | 0 Participants |
| PF-05251749 200 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion B | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion A | 0 Participants |
| PF-05251749 400 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion B | 0 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion B | 1 Participants |
| PF-05251749 750 mg AM (Part A) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion A | 0 Participants |
| Placebo (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion B | 0 Participants |
| Placebo (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion A | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion B | 0 Participants |
| PF-05251749 50 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion A | 2 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion A | 1 Participants |
| PF-05251749 200 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion B | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion A | 0 Participants |
| PF-05251749 500 mg PM (Part B) | Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) | Criterion B | 0 Participants |
Secondary
Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14
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).
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Part A) | Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14 | Day 7 | 29.42 Liter/hour (L/hr) | Geometric Coefficient of Variation 31 |
| Placebo (Part A) | Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14 | Day 14 | 30.86 Liter/hour (L/hr) | Geometric Coefficient of Variation 37 |
| Melatonin 0.5 mg PM (Part A) | Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14 | Day 7 | 23.49 Liter/hour (L/hr) | Geometric Coefficient of Variation 20 |
| Melatonin 0.5 mg PM (Part A) | Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14 | Day 14 | 23.61 Liter/hour (L/hr) | Geometric Coefficient of Variation 19 |
| PF-05251749 50 mg AM (Part A) | Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14 | Day 7 | 26.09 Liter/hour (L/hr) | Geometric Coefficient of Variation 25 |
| PF-05251749 50 mg AM (Part A) | Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14 | Day 14 | 23.53 Liter/hour (L/hr) | Geometric Coefficient of Variation 24 |
| PF-05251749 100 mg AM (Part A) | Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14 | Day 7 | 25.08 Liter/hour (L/hr) | Geometric Coefficient of Variation 31 |
| PF-05251749 100 mg AM (Part A) | Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14 | Day 14 | 29.34 Liter/hour (L/hr) | Geometric Coefficient of Variation 28 |
| PF-05251749 200 mg AM (Part A) | Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14 | Day 7 | 22.76 Liter/hour (L/hr) | Geometric Coefficient of Variation 34 |
| PF-05251749 200 mg AM (Part A) | Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14 | Day 14 | 22.51 Liter/hour (L/hr) | Geometric Coefficient of Variation 17 |
| PF-05251749 400 mg AM (Part A) | Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14 | Day 7 | 27.76 Liter/hour (L/hr) | Geometric Coefficient of Variation 21 |
| PF-05251749 400 mg AM (Part A) | Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14 | Day 14 | 26.76 Liter/hour (L/hr) | Geometric Coefficient of Variation 23 |
| PF-05251749 750 mg AM (Part A) | Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14 | Day 14 | 29.54 Liter/hour (L/hr) | Geometric Coefficient of Variation 34 |
| PF-05251749 750 mg AM (Part A) | Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14 | Day 7 | 28.50 Liter/hour (L/hr) | Geometric Coefficient of Variation 28 |
| Placebo (Part B) | Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14 | Day 7 | 26.74 Liter/hour (L/hr) | Geometric Coefficient of Variation 38 |
| Placebo (Part B) | Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14 | Day 14 | 22.82 Liter/hour (L/hr) | Geometric Coefficient of Variation 51 |
Secondary
Apparent Volume of Distribution (Vz/F) of PF-05251749 - Day 14
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).
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | Apparent Volume of Distribution (Vz/F) of PF-05251749 - Day 14 | 419.3 L | Geometric Coefficient of Variation 39 |
| Melatonin 0.5 mg PM (Part A) | Apparent Volume of Distribution (Vz/F) of PF-05251749 - Day 14 | 323.6 L | Geometric Coefficient of Variation 27 |
| PF-05251749 50 mg AM (Part A) | Apparent Volume of Distribution (Vz/F) of PF-05251749 - Day 14 | 363.9 L | Geometric Coefficient of Variation 21 |
| PF-05251749 100 mg AM (Part A) | Apparent Volume of Distribution (Vz/F) of PF-05251749 - Day 14 | 409.0 L | Geometric Coefficient of Variation 43 |
| PF-05251749 200 mg AM (Part A) | Apparent Volume of Distribution (Vz/F) of PF-05251749 - Day 14 | 353.6 L | Geometric Coefficient of Variation 17 |
| PF-05251749 400 mg AM (Part A) | Apparent Volume of Distribution (Vz/F) of PF-05251749 - Day 14 | 405.5 L | Geometric Coefficient of Variation 14 |
| PF-05251749 750 mg AM (Part A) | Apparent Volume of Distribution (Vz/F) of PF-05251749 - Day 14 | 376.5 L | Geometric Coefficient of Variation 42 |
| Placebo (Part B) | Apparent Volume of Distribution (Vz/F) of PF-05251749 - Day 14 | 343.9 L | Geometric Coefficient of Variation 36 |
Secondary
Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14.
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).
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 1 | 1430 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 39 |
| Placebo (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 14 | 1619 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 37 |
| Placebo (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 7 | 1700 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 31 |
| Melatonin 0.5 mg PM (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 14 | 4234 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 19 |
| Melatonin 0.5 mg PM (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 7 | 4260 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 20 |
| Melatonin 0.5 mg PM (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 1 | 3302 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 29 |
| PF-05251749 50 mg AM (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 14 | 8503 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 24 |
| PF-05251749 50 mg AM (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 1 | 6514 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 21 |
| PF-05251749 50 mg AM (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 7 | 7662 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 25 |
| PF-05251749 100 mg AM (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 1 | 14060 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 31 |
| PF-05251749 100 mg AM (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 7 | 15970 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 31 |
| PF-05251749 100 mg AM (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 14 | 13640 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 28 |
| PF-05251749 200 mg AM (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 7 | 32890 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 34 |
| PF-05251749 200 mg AM (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 1 | 26630 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 25 |
| PF-05251749 200 mg AM (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 14 | 33290 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 17 |
| PF-05251749 400 mg AM (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 7 | 1801 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 21 |
| PF-05251749 400 mg AM (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 1 | 1626 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 27 |
| PF-05251749 400 mg AM (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 14 | 1869 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 24 |
| PF-05251749 750 mg AM (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 7 | 7018 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 28 |
| PF-05251749 750 mg AM (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 1 | 6385 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 29 |
| PF-05251749 750 mg AM (Part A) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 14 | 6778 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 35 |
| Placebo (Part B) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 1 | 16210 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 31 |
| Placebo (Part B) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 7 | 18720 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 37 |
| Placebo (Part B) | Area Under the Concentration-Time Profile From Time 0 to Tau (AUCtau) of PF-05251749 - Days 1, 7 and 14. | Day 14 | 21950 nanogram*hour/mililiter (ng*hr/mL) | Geometric Coefficient of Variation 50 |
Secondary
Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - 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.
Time frame: Day 0 (Baseline) and Day 15
Population: The PD population was defined as all enrolled participants treated who provided at least 3 measurable salivary melatonin concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 15 | 40.0 min | Standard Deviation 61.97 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 15 | -36.7 min | Standard Deviation 93.41 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 15 | 56.3 min | Standard Deviation 54.23 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 15 | 112.5 min | Standard Deviation 75 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 15 | 100.0 min | Standard Deviation 137.7 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 15 | 115.7 min | Standard Deviation 118.02 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 15 | 150.0 min | Standard Deviation 56.12 |
| Placebo (Part B) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 15 | 49.1 min | Standard Deviation 103.29 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 15 | 150.0 min | Standard Deviation 73.48 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 15 | 135.0 min | Standard Deviation 88.49 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 15 | 210.0 min | Standard Deviation 47.43 |
90% CI: [-133.09, -9.43]
90% CI: [-76.24, 51.97]
90% CI: [12.81, 164.62]
90% CI: [-21.38, 114.35]
90% CI: [21.94, 152.66]
90% CI: [54.99, 197.45]
90% CI: [33.51, 151.21]
90% CI: [47.31, 167.27]
90% CI: [77.91, 203.3]
Secondary
Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - 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.
Time frame: Day 0 (Baseline) and Day 6.
Population: The PD (pharmacodynamic) population was defined as all enrolled participants treated who provided at least 3 measurable salivary melatonin concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 6 | 10.0 min | Standard Deviation 45.17 |
| Melatonin 0.5 mg PM (Part A) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 6 | 3.3 min | Standard Deviation 64.42 |
| PF-05251749 50 mg AM (Part A) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 6 | 11.3 min | Standard Deviation 45.18 |
| PF-05251749 100 mg AM (Part A) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 6 | 37.5 min | Standard Deviation 78.9 |
| PF-05251749 200 mg AM (Part A) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 6 | 85.0 min | Standard Deviation 83.61 |
| PF-05251749 400 mg AM (Part A) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 6 | 124.3 min | Standard Deviation 61.06 |
| PF-05251749 750 mg AM (Part A) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 6 | 150.0 min | Standard Deviation 56.12 |
| Placebo (Part B) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 6 | 13.6 min | Standard Deviation 64.85 |
| PF-05251749 50 mg PM (Part B) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 6 | 86.3 min | Standard Deviation 84 |
| PF-05251749 200 mg PM (Part B) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 6 | 135.0 min | Standard Deviation 88.49 |
| PF-05251749 500 mg PM (Part B) | Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 6 | 205.0 min | Standard Deviation 44.16 |
90% CI: [-63.09, 60.57]
90% CI: [-91.24, 36.97]
90% CI: [-32.19, 119.62]
90% CI: [-6.38, 129.35]
90% CI: [60.51, 191.23]
90% CI: [84.99, 227.45]
90% CI: [-3.57, 106.41]
90% CI: [82.76, 202.72]
90% CI: [115.11, 234.69]
Secondary
Cumulative Amount of Drug Recovered Unchanged in Urine Over Dosing Interval Tau (Aetau) of PF-05251749 - Day 14
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).
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | Cumulative Amount of Drug Recovered Unchanged in Urine Over Dosing Interval Tau (Aetau) of PF-05251749 - Day 14 | 56710 ng | Geometric Coefficient of Variation 39 |
| Melatonin 0.5 mg PM (Part A) | Cumulative Amount of Drug Recovered Unchanged in Urine Over Dosing Interval Tau (Aetau) of PF-05251749 - Day 14 | 142900 ng | Geometric Coefficient of Variation 31 |
| PF-05251749 50 mg AM (Part A) | Cumulative Amount of Drug Recovered Unchanged in Urine Over Dosing Interval Tau (Aetau) of PF-05251749 - Day 14 | 317900 ng | Geometric Coefficient of Variation 41 |
| PF-05251749 100 mg AM (Part A) | Cumulative Amount of Drug Recovered Unchanged in Urine Over Dosing Interval Tau (Aetau) of PF-05251749 - Day 14 | 404900 ng | Geometric Coefficient of Variation 59 |
| PF-05251749 200 mg AM (Part A) | Cumulative Amount of Drug Recovered Unchanged in Urine Over Dosing Interval Tau (Aetau) of PF-05251749 - Day 14 | 738300 ng | Geometric Coefficient of Variation 40 |
Secondary
Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14
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).
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 7 | 440.6 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 23 |
| Placebo (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 1 | 346.1 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 36 |
| Placebo (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 14 | 420.9 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 42 |
| Melatonin 0.5 mg PM (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 14 | 1068 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 25 |
| Melatonin 0.5 mg PM (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 7 | 971.6 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 26 |
| Melatonin 0.5 mg PM (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 1 | 838.1 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 29 |
| PF-05251749 50 mg AM (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 1 | 1600 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 33 |
| PF-05251749 50 mg AM (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 7 | 1583 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 24 |
| PF-05251749 50 mg AM (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 14 | 1907 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 17 |
| PF-05251749 100 mg AM (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 14 | 2613 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 28 |
| PF-05251749 100 mg AM (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 1 | 2465 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 36 |
| PF-05251749 100 mg AM (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 7 | 2917 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 36 |
| PF-05251749 200 mg AM (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 14 | 4726 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 19 |
| PF-05251749 200 mg AM (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 7 | 4428 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 22 |
| PF-05251749 200 mg AM (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 1 | 3990 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 17 |
| PF-05251749 400 mg AM (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 14 | 271.0 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 22 |
| PF-05251749 400 mg AM (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 1 | 219.4 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 23 |
| PF-05251749 400 mg AM (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 7 | 239.3 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 19 |
| PF-05251749 750 mg AM (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 7 | 1018 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 29 |
| PF-05251749 750 mg AM (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 1 | 898.0 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 23 |
| PF-05251749 750 mg AM (Part A) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 14 | 904.3 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 55 |
| Placebo (Part B) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 1 | 1833 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 44 |
| Placebo (Part B) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 7 | 2747 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 42 |
| Placebo (Part B) | Maximum Plasma Concentration (Cmax) of PF-05251749 - Days 1, 7 and 14 | Day 14 | 2714 nanogram/mililiter (ng/mL) | Geometric Coefficient of Variation 60 |
Secondary
Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14
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).
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Part A) | Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14 | Day 7 | 11.01 ng/mL | Geometric Coefficient of Variation 49 |
| Placebo (Part A) | Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14 | Day 14 | 11.40 ng/mL | Geometric Coefficient of Variation 51 |
| Melatonin 0.5 mg PM (Part A) | Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14 | Day 7 | 27.35 ng/mL | Geometric Coefficient of Variation 41 |
| Melatonin 0.5 mg PM (Part A) | Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14 | Day 14 | 28.89 ng/mL | Geometric Coefficient of Variation 38 |
| PF-05251749 50 mg AM (Part A) | Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14 | Day 7 | 65.88 ng/mL | Geometric Coefficient of Variation 46 |
| PF-05251749 50 mg AM (Part A) | Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14 | Day 14 | 79.56 ng/mL | Geometric Coefficient of Variation 46 |
| PF-05251749 100 mg AM (Part A) | Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14 | Day 7 | 114.9 ng/mL | Geometric Coefficient of Variation 75 |
| PF-05251749 100 mg AM (Part A) | Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14 | Day 14 | 96.98 ng/mL | Geometric Coefficient of Variation 64 |
| PF-05251749 200 mg AM (Part A) | Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14 | Day 7 | 340.3 ng/mL | Geometric Coefficient of Variation 99 |
| PF-05251749 200 mg AM (Part A) | Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14 | Day 14 | 375.7 ng/mL | Geometric Coefficient of Variation 59 |
| PF-05251749 400 mg AM (Part A) | Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14 | Day 7 | 19.48 ng/mL | Geometric Coefficient of Variation 24 |
| PF-05251749 400 mg AM (Part A) | Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14 | Day 14 | 19.11 ng/mL | Geometric Coefficient of Variation 45 |
| PF-05251749 750 mg AM (Part A) | Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14 | Day 14 | 56.77 ng/mL | Geometric Coefficient of Variation 24 |
| PF-05251749 750 mg AM (Part A) | Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14 | Day 7 | 53.88 ng/mL | Geometric Coefficient of Variation 26 |
| Placebo (Part B) | Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14 | Day 7 | 161.6 ng/mL | Geometric Coefficient of Variation 100 |
| Placebo (Part B) | Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14 | Day 14 | 178.6 ng/mL | Geometric Coefficient of Variation 105 |
Secondary
Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14
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).
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Part A) | Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14 | Day 7 | 1.272 Ratio | Geometric Coefficient of Variation 27 |
| Placebo (Part A) | Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14 | Day 14 | 1.216 Ratio | Geometric Coefficient of Variation 35 |
| Melatonin 0.5 mg PM (Part A) | Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14 | Day 7 | 1.160 Ratio | Geometric Coefficient of Variation 14 |
| Melatonin 0.5 mg PM (Part A) | Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14 | Day 14 | 1.273 Ratio | Geometric Coefficient of Variation 28 |
| PF-05251749 50 mg AM (Part A) | Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14 | Day 7 | 0.9898 Ratio | Geometric Coefficient of Variation 21 |
| PF-05251749 50 mg AM (Part A) | Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14 | Day 14 | 1.194 Ratio | Geometric Coefficient of Variation 27 |
| PF-05251749 100 mg AM (Part A) | Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14 | Day 7 | 1.161 Ratio | Geometric Coefficient of Variation 34 |
| PF-05251749 100 mg AM (Part A) | Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14 | Day 14 | 1.039 Ratio | Geometric Coefficient of Variation 20 |
| PF-05251749 200 mg AM (Part A) | Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14 | Day 7 | 1.155 Ratio | Geometric Coefficient of Variation 10 |
| PF-05251749 200 mg AM (Part A) | Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14 | Day 14 | 1.234 Ratio | Geometric Coefficient of Variation 19 |
| PF-05251749 400 mg AM (Part A) | Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14 | Day 7 | 1.093 Ratio | Geometric Coefficient of Variation 12 |
| PF-05251749 400 mg AM (Part A) | Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14 | Day 14 | 1.226 Ratio | Geometric Coefficient of Variation 13 |
| PF-05251749 750 mg AM (Part A) | Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14 | Day 14 | 0.9686 Ratio | Geometric Coefficient of Variation 47 |
| PF-05251749 750 mg AM (Part A) | Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14 | Day 7 | 1.090 Ratio | Geometric Coefficient of Variation 28 |
| Placebo (Part B) | Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14 | Day 7 | 1.422 Ratio | Geometric Coefficient of Variation 52 |
| Placebo (Part B) | Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14 | Day 14 | 1.404 Ratio | Geometric Coefficient of Variation 21 |
Secondary
Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14
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).
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Part A) | Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14 | Day 7 | 1.188 Ratio | Geometric Coefficient of Variation 16 |
| Placebo (Part A) | Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14 | Day 14 | 1.133 Ratio | Geometric Coefficient of Variation 17 |
| Melatonin 0.5 mg PM (Part A) | Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14 | Day 7 | 1.289 Ratio | Geometric Coefficient of Variation 13 |
| Melatonin 0.5 mg PM (Part A) | Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14 | Day 14 | 1.283 Ratio | Geometric Coefficient of Variation 19 |
| PF-05251749 50 mg AM (Part A) | Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14 | Day 7 | 1.176 Ratio | Geometric Coefficient of Variation 9 |
| PF-05251749 50 mg AM (Part A) | Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14 | Day 14 | 1.307 Ratio | Geometric Coefficient of Variation 15 |
| PF-05251749 100 mg AM (Part A) | Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14 | Day 7 | 1.160 Ratio | Geometric Coefficient of Variation 17 |
| PF-05251749 100 mg AM (Part A) | Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14 | Day 14 | 0.9892 Ratio | Geometric Coefficient of Variation 16 |
| PF-05251749 200 mg AM (Part A) | Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14 | Day 14 | 1.270 Ratio | Geometric Coefficient of Variation 21 |
| PF-05251749 200 mg AM (Part A) | Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14 | Day 7 | 1.255 Ratio | Geometric Coefficient of Variation 7 |
| PF-05251749 400 mg AM (Part A) | Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14 | Day 7 | 1.169 Ratio | Geometric Coefficient of Variation 12 |
| PF-05251749 400 mg AM (Part A) | Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14 | Day 14 | 1.195 Ratio | Geometric Coefficient of Variation 12 |
| PF-05251749 750 mg AM (Part A) | Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14 | Day 7 | 1.097 Ratio | Geometric Coefficient of Variation 7 |
| PF-05251749 750 mg AM (Part A) | Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14 | Day 14 | 1.061 Ratio | Geometric Coefficient of Variation 9 |
| Placebo (Part B) | Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14 | Day 14 | 1.414 Ratio | Geometric Coefficient of Variation 20 |
| Placebo (Part B) | Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14 | Day 7 | 1.205 Ratio | Geometric Coefficient of Variation 14 |
Secondary
Percentage of Dose Recovered Unchanged in Urine Over Dosing Interval Tau (Aetau%) of PF-05251749 - Day 14
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).
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | Percentage of Dose Recovered Unchanged in Urine Over Dosing Interval Tau (Aetau%) of PF-05251749 - Day 14 | 0.1133 Percentage of PF-05251749 | Geometric Coefficient of Variation 39 |
| Melatonin 0.5 mg PM (Part A) | Percentage of Dose Recovered Unchanged in Urine Over Dosing Interval Tau (Aetau%) of PF-05251749 - Day 14 | 0.1429 Percentage of PF-05251749 | Geometric Coefficient of Variation 31 |
| PF-05251749 50 mg AM (Part A) | Percentage of Dose Recovered Unchanged in Urine Over Dosing Interval Tau (Aetau%) of PF-05251749 - Day 14 | 0.1591 Percentage of PF-05251749 | Geometric Coefficient of Variation 41 |
| PF-05251749 100 mg AM (Part A) | Percentage of Dose Recovered Unchanged in Urine Over Dosing Interval Tau (Aetau%) of PF-05251749 - Day 14 | 0.1013 Percentage of PF-05251749 | Geometric Coefficient of Variation 59 |
| PF-05251749 200 mg AM (Part A) | Percentage of Dose Recovered Unchanged in Urine Over Dosing Interval Tau (Aetau%) of PF-05251749 - Day 14 | 0.09849 Percentage of PF-05251749 | Geometric Coefficient of Variation 41 |
Secondary
Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14
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).
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Part A) | Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14 | Day 7 | 40.04 Ratio | Geometric Coefficient of Variation 41 |
| Placebo (Part A) | Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14 | Day 14 | 36.93 Ratio | Geometric Coefficient of Variation 18 |
| Melatonin 0.5 mg PM (Part A) | Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14 | Day 7 | 35.54 Ratio | Geometric Coefficient of Variation 51 |
| Melatonin 0.5 mg PM (Part A) | Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14 | Day 14 | 36.98 Ratio | Geometric Coefficient of Variation 33 |
| PF-05251749 50 mg AM (Part A) | Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14 | Day 7 | 24.01 Ratio | Geometric Coefficient of Variation 39 |
| PF-05251749 50 mg AM (Part A) | Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14 | Day 14 | 23.98 Ratio | Geometric Coefficient of Variation 35 |
| PF-05251749 100 mg AM (Part A) | Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14 | Day 7 | 25.37 Ratio | Geometric Coefficient of Variation 72 |
| PF-05251749 100 mg AM (Part A) | Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14 | Day 14 | 26.92 Ratio | Geometric Coefficient of Variation 65 |
| PF-05251749 200 mg AM (Part A) | Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14 | Day 7 | 13.00 Ratio | Geometric Coefficient of Variation 81 |
| PF-05251749 200 mg AM (Part A) | Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14 | Day 14 | 12.57 Ratio | Geometric Coefficient of Variation 64 |
| PF-05251749 400 mg AM (Part A) | Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14 | Day 7 | 12.29 Ratio | Geometric Coefficient of Variation 19 |
| PF-05251749 400 mg AM (Part A) | Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14 | Day 14 | 14.17 Ratio | Geometric Coefficient of Variation 49 |
| PF-05251749 750 mg AM (Part A) | Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14 | Day 14 | 15.92 Ratio | Geometric Coefficient of Variation 34 |
| PF-05251749 750 mg AM (Part A) | Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14 | Day 7 | 18.90 Ratio | Geometric Coefficient of Variation 24 |
| Placebo (Part B) | Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14 | Day 7 | 17.02 Ratio | Geometric Coefficient of Variation 63 |
| Placebo (Part B) | Plasma Peak-to-trough Ratio (PTR) (Cmax/Cmin) of PF-05251749 - Days 7 and 14 | Day 14 | 15.20 Ratio | Geometric Coefficient of Variation 101 |
Secondary
Renal Clearance (CLr) of PF-05251749 - Day 14
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).
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | Renal Clearance (CLr) of PF-05251749 - Day 14 | 37.18 mL/hr | Geometric Coefficient of Variation 44 |
| Melatonin 0.5 mg PM (Part A) | Renal Clearance (CLr) of PF-05251749 - Day 14 | 33.76 mL/hr | Geometric Coefficient of Variation 33 |
| PF-05251749 50 mg AM (Part A) | Renal Clearance (CLr) of PF-05251749 - Day 14 | 37.39 mL/hr | Geometric Coefficient of Variation 36 |
| PF-05251749 100 mg AM (Part A) | Renal Clearance (CLr) of PF-05251749 - Day 14 | 29.73 mL/hr | Geometric Coefficient of Variation 30 |
| PF-05251749 200 mg AM (Part A) | Renal Clearance (CLr) of PF-05251749 - Day 14 | 22.15 mL/hr | Geometric Coefficient of Variation 31 |
Secondary
Terminal Half-Life (t1/2) of PF-05251749 - Day 14
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).
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | Terminal Half-Life (t1/2) of PF-05251749 - Day 14 | 9.625 hr | Standard Deviation 2.0701 |
| Melatonin 0.5 mg PM (Part A) | Terminal Half-Life (t1/2) of PF-05251749 - Day 14 | 9.630 hr | Standard Deviation 1.6523 |
| PF-05251749 50 mg AM (Part A) | Terminal Half-Life (t1/2) of PF-05251749 - Day 14 | 10.91 hr | Standard Deviation 1.4405 |
| PF-05251749 100 mg AM (Part A) | Terminal Half-Life (t1/2) of PF-05251749 - Day 14 | 9.940 hr | Standard Deviation 2.3215 |
| PF-05251749 200 mg AM (Part A) | Terminal Half-Life (t1/2) of PF-05251749 - Day 14 | 11.20 hr | Standard Deviation 3.0942 |
| PF-05251749 400 mg AM (Part A) | Terminal Half-Life (t1/2) of PF-05251749 - Day 14 | 10.62 hr | Standard Deviation 1.4922 |
| PF-05251749 750 mg AM (Part A) | Terminal Half-Life (t1/2) of PF-05251749 - Day 14 | 8.878 hr | Standard Deviation 0.93101 |
| Placebo (Part B) | Terminal Half-Life (t1/2) of PF-05251749 - Day 14 | 10.62 hr | Standard Deviation 2.1519 |
Secondary
Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14
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).
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 1 | 1.00 hr |
| Placebo (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 14 | 1.00 hr |
| Placebo (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 7 | 0.500 hr |
| Melatonin 0.5 mg PM (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 14 | 1.00 hr |
| Melatonin 0.5 mg PM (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 7 | 1.00 hr |
| Melatonin 0.5 mg PM (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 1 | 1.00 hr |
| PF-05251749 50 mg AM (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 14 | 1.00 hr |
| PF-05251749 50 mg AM (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 1 | 1.00 hr |
| PF-05251749 50 mg AM (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 7 | 1.00 hr |
| PF-05251749 100 mg AM (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 1 | 1.00 hr |
| PF-05251749 100 mg AM (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 7 | 1.00 hr |
| PF-05251749 100 mg AM (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 14 | 1.00 hr |
| PF-05251749 200 mg AM (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 7 | 1.50 hr |
| PF-05251749 200 mg AM (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 1 | 1.00 hr |
| PF-05251749 200 mg AM (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 14 | 1.00 hr |
| PF-05251749 400 mg AM (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 7 | 1.00 hr |
| PF-05251749 400 mg AM (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 1 | 1.75 hr |
| PF-05251749 400 mg AM (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 14 | 1.00 hr |
| PF-05251749 750 mg AM (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 7 | 0.750 hr |
| PF-05251749 750 mg AM (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 1 | 1.00 hr |
| PF-05251749 750 mg AM (Part A) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 14 | 2.00 hr |
| Placebo (Part B) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 1 | 1.00 hr |
| Placebo (Part B) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 7 | 1.50 hr |
| Placebo (Part B) | Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 | Day 14 | 2.00 hr |