Trial Outcomes & Findings for Multiple Dose Study Of BIIB118 (PF-05251749) In Healthy Volunteers (NCT NCT02691702)

NCT ID: NCT02691702

Last Updated: 2021-02-17

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 97 participants
• Primary outcome timeframe: 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).
• Results posted on: 2021-02-17

Participant Flow

Participant milestones

Measure	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.
Overall Study STARTED	10	11	8	8	8	8	8	12	8	8	8
Overall Study COMPLETED	8	10	7	8	8	5	5	12	6	6	6
Overall Study NOT COMPLETED	2	1	1	0	0	3	3	0	2	2	2

Reasons for withdrawal

Measure	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.
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 Withdrawal by Subject	1	1	0	0	0	1	2	0	0	0	0
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

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo (Part A) n=10 Participants 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.	Melatonin 0.5 mg PM (Part A) n=11 Participants 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.	PF-05251749 50 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=12 Participants 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.	PF-05251749 50 mg PM (Part B) n=8 Participants 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.	PF-05251749 200 mg PM (Part B) n=8 Participants 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.	PF-05251749 500 mg PM (Part B) n=8 Participants Participants received PF-05251749 500 mg orally at 6:00 PM outside a window of ±2 hours of giving food. Dosing continued every day until the final dose was administered on Day 14.	Total n=97 Participants Total of all reporting groups
Age, Customized < 18 years	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	0 participants n=8 Participants	0 participants n=8 Participants	0 participants n=24 Participants	0 participants n=42 Participants	0 participants n=42 Participants	0 participants n=42 Participants	0 participants n=42 Participants
Age, Customized 18-44 years	6 participants n=5 Participants	7 participants n=7 Participants	1 participants n=5 Participants	5 participants n=4 Participants	0 participants n=21 Participants	3 participants n=8 Participants	4 participants n=8 Participants	7 participants n=24 Participants	3 participants n=42 Participants	6 participants n=42 Participants	4 participants n=42 Participants	46 participants n=42 Participants
Age, Customized 45-64 years	4 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants	3 participants n=4 Participants	8 participants n=21 Participants	5 participants n=8 Participants	4 participants n=8 Participants	5 participants n=24 Participants	5 participants n=42 Participants	2 participants n=42 Participants	4 participants n=42 Participants	51 participants n=42 Participants
Age, Customized >= 65	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	0 participants n=8 Participants	0 participants n=8 Participants	0 participants n=24 Participants	0 participants n=42 Participants	0 participants n=42 Participants	0 participants n=42 Participants	0 participants n=42 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	5 Participants n=21 Participants	1 Participants n=8 Participants	3 Participants n=8 Participants	2 Participants n=24 Participants	1 Participants n=42 Participants	0 Participants n=42 Participants	2 Participants n=42 Participants	15 Participants n=42 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	11 Participants n=7 Participants	8 Participants n=5 Participants	8 Participants n=4 Participants	3 Participants n=21 Participants	7 Participants n=8 Participants	5 Participants n=8 Participants	10 Participants n=24 Participants	7 Participants n=42 Participants	8 Participants n=42 Participants	6 Participants n=42 Participants	82 Participants n=42 Participants
Race/Ethnicity, Customized White	7 Participants n=5 Participants	9 Participants n=7 Participants	6 Participants n=5 Participants	8 Participants n=4 Participants	7 Participants n=21 Participants	7 Participants n=8 Participants	8 Participants n=8 Participants	10 Participants n=24 Participants	7 Participants n=42 Participants	6 Participants n=42 Participants	7 Participants n=42 Participants	82 Participants n=42 Participants
Race/Ethnicity, Customized Black	3 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=8 Participants	0 Participants n=8 Participants	2 Participants n=24 Participants	1 Participants n=42 Participants	2 Participants n=42 Participants	1 Participants n=42 Participants	15 Participants n=42 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=10 Participants 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.	PF-05251749 100 mg AM (Part A) n=11 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=12 Participants 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.	PF-05251749 50 mg PM (Part B) n=8 Participants 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.	PF-05251749 200 mg PM (Part B) n=8 Participants 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.	PF-05251749 500 mg PM (Part B) n=8 Participants 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.
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 14.480	5.88 Units on a scale Standard Deviation 8.943	6.46 Units on a scale Standard Deviation 11.092	6.51 Units on a scale Standard Deviation 11.209	3.48 Units on a scale Standard Deviation 12.533	6.23 Units on a scale Standard Deviation 8.043	-14.45 Units on a scale Standard Deviation 17.182	-0.46 Units on a scale Standard Deviation 7.105	-0.25 Units on a scale Standard Deviation 6.349	0.65 Units on a scale Standard Deviation 8.135	-3.00 Units on a scale Standard Deviation 5.143
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	3.76 Units on a scale Standard Deviation 11.243	2.21 Units on a scale Standard Deviation 12.305	6.96 Units on a scale Standard Deviation 9.630	3.39 Units on a scale Standard Deviation 12.541	6.54 Units on a scale Standard Deviation 12.898	-2.14 Units on a scale Standard Deviation 9.437	1.23 Units on a scale Standard Deviation 6.356	-0.50 Units on a scale Standard Deviation 6.514	0.23 Units on a scale Standard Deviation 5.771	-0.79 Units on a scale Standard Deviation 5.109
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	-0.63 Units on a scale Standard Deviation 20.162	4.03 Units on a scale Standard Deviation 14.212	7.54 Units on a scale Standard Deviation 9.519	2.76 Units on a scale Standard Deviation 6.221	8.04 Units on a scale Standard Deviation 11.784	-10.92 Units on a scale Standard Deviation 15.343	1.57 Units on a scale Standard Deviation 5.817	-1.25 Units on a scale Standard Deviation 6.743	-3.00 Units on a scale Standard Deviation 11.517	-4.93 Units on a scale Standard Deviation 9.924
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	4.76 Units on a scale Standard Deviation 13.174	5.83 Units on a scale Standard Deviation 12.879	6.20 Units on a scale Standard Deviation 6.462	4.83 Units on a scale Standard Deviation 7.288	7.51 Units on a scale Standard Deviation 10.848	-9.08 Units on a scale Standard Deviation 21.071	1.31 Units on a scale Standard Deviation 5.667	-0.09 Units on a scale Standard Deviation 7.507	-0.82 Units on a scale Standard Deviation 7.100	-0.53 Units on a scale Standard Deviation 6.265
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	4.97 Units on a scale Standard Deviation 10.320	5.68 Units on a scale Standard Deviation 12.631	1.50 Units on a scale Standard Deviation 5.458	2.96 Units on a scale Standard Deviation 10.782	8.30 Units on a scale Standard Deviation 11.045	5.12 Units on a scale Standard Deviation 9.507	1.43 Units on a scale Standard Deviation 5.532	-1.93 Units on a scale Standard Deviation 9.227	0.18 Units on a scale Standard Deviation 10.212	-0.89 Units on a scale Standard Deviation 8.264
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	7.18 Units on a scale Standard Deviation 11.543	6.03 Units on a scale Standard Deviation 13.385	1.75 Units on a scale Standard Deviation 14.316	4.15 Units on a scale Standard Deviation 11.839	6.16 Units on a scale Standard Deviation 11.063	0.42 Units on a scale Standard Deviation 5.971	2.83 Units on a scale Standard Deviation 5.437	0.28 Units on a scale Standard Deviation 3.998	2.25 Units on a scale Standard Deviation 5.623	-3.33 Units on a scale Standard Deviation 8.503
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 15.940	7.38 Units on a scale Standard Deviation 10.892	3.51 Units on a scale Standard Deviation 16.583	9.13 Units on a scale Standard Deviation 10.092	2.13 Units on a scale Standard Deviation 14.382	8.57 Units on a scale Standard Deviation 12.525	9.20 Units on a scale Standard Deviation 8.385	1.62 Units on a scale Standard Deviation 5.057	1.07 Units on a scale Standard Deviation 4.223	3.15 Units on a scale Standard Deviation 3.971	-1.93 Units on a scale Standard Deviation 6.736
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	10.64 Units on a scale Standard Deviation 15.791	6.80 Units on a scale Standard Deviation 15.431	9.04 Units on a scale Standard Deviation 9.736	3.93 Units on a scale Standard Deviation 11.931	8.39 Units on a scale Standard Deviation 11.696	9.88 Units on a scale Standard Deviation 8.410	1.33 Units on a scale Standard Deviation 6.533	1.02 Units on a scale Standard Deviation 3.170	8.37 Units on a scale Standard Deviation 13.401	5.61 Units on a scale Standard Deviation 6.812
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	7.50 Units on a scale Standard Deviation 8.043	6.71 Units on a scale Standard Deviation 12.314	3.50 Units on a scale Standard Deviation 10.071	4.58 Units on a scale Standard Deviation 9.472	4.05 Units on a scale Standard Deviation 6.038	1.49 Units on a scale Standard Deviation 11.514	-0.08 Units on a scale Standard Deviation 6.382	-2.83 Units on a scale Standard Deviation 7.314	-6.04 Units on a scale Standard Deviation 10.085	-1.93 Units on a scale Standard Deviation 7.953

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=10 Participants 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.	PF-05251749 100 mg AM (Part A) n=11 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=12 Participants 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.	PF-05251749 50 mg PM (Part B) n=8 Participants 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.	PF-05251749 200 mg PM (Part B) n=8 Participants 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.	PF-05251749 500 mg PM (Part B) n=8 Participants 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.
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	1.45 Units on a scale Standard Deviation 3.940	3.56 Units on a scale Standard Deviation 16.668	13.88 Units on a scale Standard Deviation 20.662	1.56 Units on a scale Standard Deviation 1.522	2.25 Units on a scale Standard Deviation 5.175	1.81 Units on a scale Standard Deviation 9.509	-0.38 Units on a scale Standard Deviation 2.630	-2.06 Units on a scale Standard Deviation 6.032	-15.31 Units on a scale Standard Deviation 20.114	-0.56 Units on a scale Standard Deviation 3.774
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	4.00 Units on a scale Standard Deviation 12.092	7.50 Units on a scale Standard Deviation 24.391	16.13 Units on a scale Standard Deviation 22.448	-1.75 Units on a scale Standard Deviation 8.302	1.50 Units on a scale Standard Deviation 1.732	-11.25 Units on a scale Standard Deviation 18.030	1.25 Units on a scale Standard Deviation 8.081	-1.75 Units on a scale Standard Deviation 4.652	-5.83 Units on a scale Standard Deviation 10.405	1.19 Units on a scale Standard Deviation 5.035
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	-3.85 Units on a scale Standard Deviation 11.255	8.63 Units on a scale Standard Deviation 24.013	13.44 Units on a scale Standard Deviation 21.089	1.06 Units on a scale Standard Deviation 2.129	0.50 Units on a scale Standard Deviation 3.948	-12.10 Units on a scale Standard Deviation 25.289	1.08 Units on a scale Standard Deviation 7.902	-5.19 Units on a scale Standard Deviation 14.258	-4.00 Units on a scale Standard Deviation 4.950	3.36 Units on a scale Standard Deviation 10.351
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	0.40 Units on a scale Standard Deviation 10.572	7.56 Units on a scale Standard Deviation 24.693	14.44 Units on a scale Standard Deviation 20.859	1.44 Units on a scale Standard Deviation 1.348	2.14 Units on a scale Standard Deviation 2.593	-13.30 Units on a scale Standard Deviation 26.537	1.54 Units on a scale Standard Deviation 8.349	-2.31 Units on a scale Standard Deviation 6.954	-8.58 Units on a scale Standard Deviation 9.881	-1.21 Units on a scale Standard Deviation 12.419
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	0.75 Units on a scale Standard Deviation 5.149	7.56 Units on a scale Standard Deviation 24.943	13.75 Units on a scale Standard Deviation 20.707	1.81 Units on a scale Standard Deviation 1.751	1.71 Units on a scale Standard Deviation 2.464	-11.90 Units on a scale Standard Deviation 27.220	2.46 Units on a scale Standard Deviation 7.356	-0.57 Units on a scale Standard Deviation 6.194	-5.33 Units on a scale Standard Deviation 11.725	0.21 Units on a scale Standard Deviation 16.820
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	2.30 Units on a scale Standard Deviation 8.629	6.88 Units on a scale Standard Deviation 25.531	14.69 Units on a scale Standard Deviation 21.457	1.94 Units on a scale Standard Deviation 2.008	-4.29 Units on a scale Standard Deviation 14.502	-10.30 Units on a scale Standard Deviation 27.174	2.88 Units on a scale Standard Deviation 7.227	-2.58 Units on a scale Standard Deviation 7.902	-4.00 Units on a scale Standard Deviation 9.391	2.86 Units on a scale Standard Deviation 11.607
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	2.00 Units on a scale Standard Deviation 6.245	8.06 Units on a scale Standard Deviation 24.282	15.25 Units on a scale Standard Deviation 21.471	1.44 Units on a scale Standard Deviation 2.178	2.71 Units on a scale Standard Deviation 2.498	-3.20 Units on a scale Standard Deviation 8.213	3.54 Units on a scale Standard Deviation 6.600	-1.08 Units on a scale Standard Deviation 4.042	-4.75 Units on a scale Standard Deviation 9.837	4.07 Units on a scale Standard Deviation 9.467
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	1.85 Units on a scale Standard Deviation 8.564	9.63 Units on a scale Standard Deviation 23.242	14.81 Units on a scale Standard Deviation 21.032	-3.25 Units on a scale Standard Deviation 16.160	2.50 Units on a scale Standard Deviation 3.594	6.80 Units on a scale Standard Deviation 12.065	2.79 Units on a scale Standard Deviation 7.402	0.17 Units on a scale Standard Deviation 3.502	0.58 Units on a scale Standard Deviation 3.456	4.86 Units on a scale Standard Deviation 10.327
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	0.30 Units on a scale Standard Deviation 11.622	8.94 Units on a scale Standard Deviation 23.542	16.13 Units on a scale Standard Deviation 21.922	2.00 Units on a scale Standard Deviation 1.927	2.21 Units on a scale Standard Deviation 2.706	0.90 Units on a scale Standard Deviation 21.927	2.88 Units on a scale Standard Deviation 7.441	-0.08 Units on a scale Standard Deviation 2.957	2.67 Units on a scale Standard Deviation 9.548	6.93 Units on a scale Standard Deviation 11.745

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=10 Participants 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.	PF-05251749 100 mg AM (Part A) n=11 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=12 Participants 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.	PF-05251749 50 mg PM (Part B) n=8 Participants 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.	PF-05251749 200 mg PM (Part B) n=8 Participants 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.	PF-05251749 500 mg PM (Part B) n=8 Participants 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.
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 4.480	5.16 Units on a scale Standard Deviation 15.927	2.20 Units on a scale Standard Deviation 12.642	2.03 Units on a scale Standard Deviation 5.579	5.55 Units on a scale Standard Deviation 13.357	3.25 Units on a scale Standard Deviation 7.391	0.50 Units on a scale Standard Deviation 8.384	0.32 Units on a scale Standard Deviation 5.402	-1.43 Units on a scale Standard Deviation 5.432	-7.80 Units on a scale Standard Deviation 11.921	-2.85 Units on a scale Standard Deviation 10.557
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	2.78 Units on a scale Standard Deviation 15.744	1.85 Units on a scale Standard Deviation 11.244	2.30 Units on a scale Standard Deviation 12.752	6.84 Units on a scale Standard Deviation 12.834	5.23 Units on a scale Standard Deviation 7.530	-12.73 Units on a scale Standard Deviation 13.168	1.25 Units on a scale Standard Deviation 5.218	-3.13 Units on a scale Standard Deviation 8.269	-8.60 Units on a scale Standard Deviation 12.057	-1.73 Units on a scale Standard Deviation 3.798
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	-1.86 Units on a scale Standard Deviation 12.644	0.93 Units on a scale Standard Deviation 12.440	6.20 Units on a scale Standard Deviation 9.953	7.30 Units on a scale Standard Deviation 13.407	5.83 Units on a scale Standard Deviation 10.032	-6.68 Units on a scale Standard Deviation 11.595	-0.45 Units on a scale Standard Deviation 7.295	-0.38 Units on a scale Standard Deviation 4.313	-4.90 Units on a scale Standard Deviation 6.395	-3.06 Units on a scale Standard Deviation 3.878
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	3.30 Units on a scale Standard Deviation 14.328	6.65 Units on a scale Standard Deviation 11.230	3.83 Units on a scale Standard Deviation 8.980	6.30 Units on a scale Standard Deviation 8.661	5.83 Units on a scale Standard Deviation 9.082	-10.84 Units on a scale Standard Deviation 11.344	1.32 Units on a scale Standard Deviation 5.811	-2.83 Units on a scale Standard Deviation 7.719	-2.87 Units on a scale Standard Deviation 3.110	-10.00 Units on a scale Standard Deviation 16.401
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	2.12 Units on a scale Standard Deviation 16.892	3.50 Units on a scale Standard Deviation 11.745	5.13 Units on a scale Standard Deviation 8.561	8.13 Units on a scale Standard Deviation 12.784	6.11 Units on a scale Standard Deviation 8.896	-9.92 Units on a scale Standard Deviation 17.802	1.50 Units on a scale Standard Deviation 5.784	-0.29 Units on a scale Standard Deviation 4.783	-3.97 Units on a scale Standard Deviation 7.816	-2.94 Units on a scale Standard Deviation 1.672
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	4.64 Units on a scale Standard Deviation 14.753	5.13 Units on a scale Standard Deviation 8.037	2.85 Units on a scale Standard Deviation 8.854	6.33 Units on a scale Standard Deviation 13.084	3.97 Units on a scale Standard Deviation 11.878	-0.84 Units on a scale Standard Deviation 7.942	2.17 Units on a scale Standard Deviation 6.178	-2.20 Units on a scale Standard Deviation 6.950	-3.50 Units on a scale Standard Deviation 8.772	-2.09 Units on a scale Standard Deviation 7.061
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	5.54 Units on a scale Standard Deviation 14.101	3.63 Units on a scale Standard Deviation 12.086	6.88 Units on a scale Standard Deviation 8.256	5.03 Units on a scale Standard Deviation 14.154	4.46 Units on a scale Standard Deviation 6.410	-2.96 Units on a scale Standard Deviation 4.883	2.10 Units on a scale Standard Deviation 5.706	-0.73 Units on a scale Standard Deviation 3.259	-2.03 Units on a scale Standard Deviation 4.094	-2.89 Units on a scale Standard Deviation 6.350
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	6.52 Units on a scale Standard Deviation 14.121	4.70 Units on a scale Standard Deviation 14.515	7.13 Units on a scale Standard Deviation 9.288	3.25 Units on a scale Standard Deviation 14.971	6.51 Units on a scale Standard Deviation 9.306	2.80 Units on a scale Standard Deviation 7.053	0.78 Units on a scale Standard Deviation 7.989	-0.30 Units on a scale Standard Deviation 3.067	3.90 Units on a scale Standard Deviation 10.749	-1.26 Units on a scale Standard Deviation 5.991
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	7.48 Units on a scale Standard Deviation 19.847	7.36 Units on a scale Standard Deviation 12.735	10.70 Units on a scale Standard Deviation 6.978	4.95 Units on a scale Standard Deviation 15.441	3.63 Units on a scale Standard Deviation 6.738	3.00 Units on a scale Standard Deviation 5.829	0.93 Units on a scale Standard Deviation 7.767	-0.20 Units on a scale Standard Deviation 2.154	6.60 Units on a scale Standard Deviation 17.980	1.74 Units on a scale Standard Deviation 5.754

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=10 Participants 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.	PF-05251749 100 mg AM (Part A) n=11 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=12 Participants 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.	PF-05251749 50 mg PM (Part B) n=8 Participants 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.	PF-05251749 200 mg PM (Part B) n=8 Participants 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.	PF-05251749 500 mg PM (Part B) n=8 Participants 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.
Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) Day 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) Day 7	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) Day 14	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) Day 16	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With New Onset and Worsening of Post-baseline Suicidality for Columbia Suicide Severity Rating Scale (C-SSRS) Follow-up	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=10 Participants 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.	PF-05251749 100 mg AM (Part A) n=11 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=12 Participants 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.	PF-05251749 50 mg PM (Part B) n=8 Participants 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.	PF-05251749 200 mg PM (Part B) n=8 Participants 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.	PF-05251749 500 mg PM (Part B) n=8 Participants 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.
Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causalities)	4 Participants	3 Participants	3 Participants	1 Participants	5 Participants	7 Participants	7 Participants	3 Participants	5 Participants	2 Participants	8 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=10 Participants 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.	PF-05251749 100 mg AM (Part A) n=11 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=12 Participants 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.	PF-05251749 50 mg PM (Part B) n=8 Participants 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.	PF-05251749 200 mg PM (Part B) n=8 Participants 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.	PF-05251749 500 mg PM (Part B) n=8 Participants 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.
Number of Participants With Treatment-Emergent Adverse Events (AEs) (Treatment Related)	1 Participants	2 Participants	2 Participants	1 Participants	1 Participants	5 Participants	7 Participants	2 Participants	4 Participants	2 Participants	8 Participants

PRIMARY outcome

Timeframe: 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.

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)

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=10 Participants 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.	PF-05251749 100 mg AM (Part A) n=11 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=12 Participants 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.	PF-05251749 50 mg PM (Part B) n=8 Participants 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.	PF-05251749 200 mg PM (Part B) n=8 Participants 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.	PF-05251749 500 mg PM (Part B) n=8 Participants 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.
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	2 Participants	8 Participants	1 Participants	2 Participants	4 Participants	4 Participants	7 Participants	8 Participants	5 Participants	5 Participants	7 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=10 Participants 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.	PF-05251749 100 mg AM (Part A) n=11 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=12 Participants 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.	PF-05251749 50 mg PM (Part B) n=8 Participants 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.	PF-05251749 200 mg PM (Part B) n=8 Participants 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.	PF-05251749 500 mg PM (Part B) n=8 Participants 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.
Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) Supine Systolic BP < 90 mmHg	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) Supine Diastolic BP < 50 mmHg	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) Supine Pulse Rate < 40 BPM	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Data Meeting Categorical Criteria (Absolute Values) Supine Pulse Rate > 120 BPM	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=10 Participants 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.	PF-05251749 100 mg AM (Part A) n=11 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=12 Participants 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.	PF-05251749 50 mg PM (Part B) n=8 Participants 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.	PF-05251749 200 mg PM (Part B) n=8 Participants 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.	PF-05251749 500 mg PM (Part B) n=8 Participants 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.
Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) Criterion A	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants
Number of Participants With Vital Signs Data Meeting Categorical Criteria (Increases From Baseline) Criterion B	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=10 Participants 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.	PF-05251749 100 mg AM (Part A) n=11 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=12 Participants 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.	PF-05251749 50 mg PM (Part B) n=8 Participants 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.	PF-05251749 200 mg PM (Part B) n=8 Participants 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.	PF-05251749 500 mg PM (Part B) n=8 Participants 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.
Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) Criterion B	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Data Meeting Categorical Criteria (Decrease From Baseline) Criterion A	2 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	2 Participants	1 Participants	1 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=10 Participants 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.	PF-05251749 100 mg AM (Part A) n=11 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=12 Participants 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.	PF-05251749 50 mg PM (Part B) n=8 Participants 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.	PF-05251749 200 mg PM (Part B) n=8 Participants 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.	PF-05251749 500 mg PM (Part B) n=8 Participants 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.
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) Criterion A	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) Criterion B	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) Criterion C	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) Criterion D	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) Criterion E	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) Criterion F	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) Criterion G	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) Criterion H	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Absolute Values) Criterion I	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=10 Participants 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.	PF-05251749 100 mg AM (Part A) n=11 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=12 Participants 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.	PF-05251749 50 mg PM (Part B) n=8 Participants 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.	PF-05251749 200 mg PM (Part B) n=8 Participants 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.	PF-05251749 500 mg PM (Part B) n=8 Participants 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.
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) Criterion A	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) Criterion B	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) Criterion C	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	2 Participants	3 Participants	1 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) Criterion D	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) Criterion E	0 Participants	0 Participants	2 Participants	0 Participants	1 Participants	0 Participants	1 Participants	2 Participants	3 Participants	1 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria (Increase From Baseline) Criterion F	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=10 Participants 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.	PF-05251749 100 mg AM (Part A) n=11 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=12 Participants 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.	PF-05251749 50 mg PM (Part B) n=8 Participants 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.	PF-05251749 200 mg PM (Part B) n=8 Participants 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.	PF-05251749 500 mg PM (Part B) n=8 Participants 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.
Number of Participants With New/Intensified Physical Examination Findings	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=10 Participants 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.	PF-05251749 100 mg AM (Part A) n=11 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=12 Participants 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.	PF-05251749 50 mg PM (Part B) n=8 Participants 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.	PF-05251749 200 mg PM (Part B) n=8 Participants 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.	PF-05251749 500 mg PM (Part B) n=8 Participants 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.
Number of Participants With New/Intensified Neurological Examination Findings	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=8 Participants 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.	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.	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.	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.
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	838.1 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 29	1600 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 33	2465 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 36	3990 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 17	219.4 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 23	898.0 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 23	1833 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 44	—	—	—
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	971.6 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 26	1583 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 24	2917 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 36	4428 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 22	239.3 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 19	1018 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 29	2747 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 42	—	—	—
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	1068 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 25	1907 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 17	2613 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 28	4726 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 19	271.0 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 22	904.3 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 55	2714 nanogram/mililiter (ng/mL) Geometric Coefficient of Variation 60	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=8 Participants 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.	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.	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.	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.
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	3302 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 29	6514 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 21	14060 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 31	26630 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 25	1626 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 27	6385 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 29	16210 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 31	—	—	—
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	4260 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 20	7662 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 25	15970 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 31	32890 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 34	1801 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 21	7018 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 28	18720 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 37	—	—	—
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	4234 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 19	8503 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 24	13640 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 28	33290 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 17	1869 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 24	6778 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 35	21950 nanogram*hour/mililiter (ng*hr/mL) Geometric Coefficient of Variation 50	—	—	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=8 Participants 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.	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.	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.	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.
Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 Day 14	1.00 hr Interval 0.5 to 1.0	1.00 hr Interval 0.5 to 1.0	1.00 hr Interval 0.5 to 1.5	1.00 hr Interval 0.5 to 2.0	1.00 hr Interval 0.5 to 1.0	1.00 hr Interval 0.5 to 1.5	2.00 hr Interval 0.5 to 3.0	2.00 hr Interval 1.0 to 3.0	—	—	—
Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 Day 7	0.500 hr Interval 0.5 to 2.0	1.00 hr Interval 0.5 to 1.5	1.00 hr Interval 1.0 to 2.0	1.00 hr Interval 1.0 to 3.0	1.50 hr Interval 1.0 to 3.0	1.00 hr Interval 1.0 to 3.0	0.750 hr Interval 0.45 to 3.0	1.50 hr Interval 0.5 to 3.0	—	—	—
Time at Which Cmax Occurred (Tmax) of PF-05251749 - Days 1, 7 and 14 Day 1	1.00 hr Interval 0.5 to 1.0	1.00 hr Interval 0.5 to 1.5	1.00 hr Interval 0.5 to 1.0	1.00 hr Interval 1.0 to 3.0	1.00 hr Interval 0.5 to 3.0	1.75 hr Interval 1.0 to 3.0	1.00 hr Interval 0.5 to 3.0	1.00 hr Interval 0.5 to 12.0	—	—	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=8 Participants 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.	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.	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.	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.
Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14 Day 7	29.42 Liter/hour (L/hr) Geometric Coefficient of Variation 31	23.49 Liter/hour (L/hr) Geometric Coefficient of Variation 20	26.09 Liter/hour (L/hr) Geometric Coefficient of Variation 25	25.08 Liter/hour (L/hr) Geometric Coefficient of Variation 31	22.76 Liter/hour (L/hr) Geometric Coefficient of Variation 34	27.76 Liter/hour (L/hr) Geometric Coefficient of Variation 21	28.50 Liter/hour (L/hr) Geometric Coefficient of Variation 28	26.74 Liter/hour (L/hr) Geometric Coefficient of Variation 38	—	—	—
Apparent Clearance (CL/F) of PF-05251749 - Days 7 and 14 Day 14	30.86 Liter/hour (L/hr) Geometric Coefficient of Variation 37	23.61 Liter/hour (L/hr) Geometric Coefficient of Variation 19	23.53 Liter/hour (L/hr) Geometric Coefficient of Variation 24	29.34 Liter/hour (L/hr) Geometric Coefficient of Variation 28	22.51 Liter/hour (L/hr) Geometric Coefficient of Variation 17	26.76 Liter/hour (L/hr) Geometric Coefficient of Variation 23	29.54 Liter/hour (L/hr) Geometric Coefficient of Variation 34	22.82 Liter/hour (L/hr) Geometric Coefficient of Variation 51	—	—	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=8 Participants 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.	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.	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.	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.
Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14 Day 7	11.01 ng/mL Geometric Coefficient of Variation 49	27.35 ng/mL Geometric Coefficient of Variation 41	65.88 ng/mL Geometric Coefficient of Variation 46	114.9 ng/mL Geometric Coefficient of Variation 75	340.3 ng/mL Geometric Coefficient of Variation 99	19.48 ng/mL Geometric Coefficient of Variation 24	53.88 ng/mL Geometric Coefficient of Variation 26	161.6 ng/mL Geometric Coefficient of Variation 100	—	—	—
Minimum Concentration Observed (Cmin) of PF-05251749 - Days 7 and 14 Day 14	11.40 ng/mL Geometric Coefficient of Variation 51	28.89 ng/mL Geometric Coefficient of Variation 38	79.56 ng/mL Geometric Coefficient of Variation 46	96.98 ng/mL Geometric Coefficient of Variation 64	375.7 ng/mL Geometric Coefficient of Variation 59	19.11 ng/mL Geometric Coefficient of Variation 45	56.77 ng/mL Geometric Coefficient of Variation 24	178.6 ng/mL Geometric Coefficient of Variation 105	—	—	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=8 Participants 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.	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.	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.	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.
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	35.54 Ratio Geometric Coefficient of Variation 51	24.01 Ratio Geometric Coefficient of Variation 39	25.37 Ratio Geometric Coefficient of Variation 72	13.00 Ratio Geometric Coefficient of Variation 81	12.29 Ratio Geometric Coefficient of Variation 19	18.90 Ratio Geometric Coefficient of Variation 24	17.02 Ratio Geometric Coefficient of Variation 63	—	—	—
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	36.98 Ratio Geometric Coefficient of Variation 33	23.98 Ratio Geometric Coefficient of Variation 35	26.92 Ratio Geometric Coefficient of Variation 65	12.57 Ratio Geometric Coefficient of Variation 64	14.17 Ratio Geometric Coefficient of Variation 49	15.92 Ratio Geometric Coefficient of Variation 34	15.20 Ratio Geometric Coefficient of Variation 101	—	—	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=8 Participants 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.	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.	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.	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.
Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14 Day 7	1.188 Ratio Geometric Coefficient of Variation 16	1.289 Ratio Geometric Coefficient of Variation 13	1.176 Ratio Geometric Coefficient of Variation 9	1.160 Ratio Geometric Coefficient of Variation 17	1.255 Ratio Geometric Coefficient of Variation 7	1.169 Ratio Geometric Coefficient of Variation 12	1.097 Ratio Geometric Coefficient of Variation 7	1.205 Ratio Geometric Coefficient of Variation 14	—	—	—
Observed Accumulation Ratio (Rac) of PF-05251749 -Days 7 and 14 Day 14	1.133 Ratio Geometric Coefficient of Variation 17	1.283 Ratio Geometric Coefficient of Variation 19	1.307 Ratio Geometric Coefficient of Variation 15	0.9892 Ratio Geometric Coefficient of Variation 16	1.270 Ratio Geometric Coefficient of Variation 21	1.195 Ratio Geometric Coefficient of Variation 12	1.061 Ratio Geometric Coefficient of Variation 9	1.414 Ratio Geometric Coefficient of Variation 20	—	—	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=8 Participants 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.	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.	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.	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.
Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14 Day 7	1.272 Ratio Geometric Coefficient of Variation 27	1.160 Ratio Geometric Coefficient of Variation 14	0.9898 Ratio Geometric Coefficient of Variation 21	1.161 Ratio Geometric Coefficient of Variation 34	1.155 Ratio Geometric Coefficient of Variation 10	1.093 Ratio Geometric Coefficient of Variation 12	1.090 Ratio Geometric Coefficient of Variation 28	1.422 Ratio Geometric Coefficient of Variation 52	—	—	—
Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-05251749 - Days 7 and 14 Day 14	1.216 Ratio Geometric Coefficient of Variation 35	1.273 Ratio Geometric Coefficient of Variation 28	1.194 Ratio Geometric Coefficient of Variation 27	1.039 Ratio Geometric Coefficient of Variation 20	1.234 Ratio Geometric Coefficient of Variation 19	1.226 Ratio Geometric Coefficient of Variation 13	0.9686 Ratio Geometric Coefficient of Variation 47	1.404 Ratio Geometric Coefficient of Variation 21	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=8 Participants 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.	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.	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.	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.
Terminal Half-Life (t1/2) of PF-05251749 - Day 14	9.625 hr Standard Deviation 2.0701	9.630 hr Standard Deviation 1.6523	10.91 hr Standard Deviation 1.4405	9.940 hr Standard Deviation 2.3215	11.20 hr Standard Deviation 3.0942	10.62 hr Standard Deviation 1.4922	8.878 hr Standard Deviation 0.93101	10.62 hr Standard Deviation 2.1519	—	—	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=8 Participants 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.	Placebo (Part B) n=8 Participants 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.	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.	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.	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.
Apparent Volume of Distribution (Vz/F) of PF-05251749 - Day 14	419.3 L Geometric Coefficient of Variation 39	323.6 L Geometric Coefficient of Variation 27	363.9 L Geometric Coefficient of Variation 21	409.0 L Geometric Coefficient of Variation 43	353.6 L Geometric Coefficient of Variation 17	405.5 L Geometric Coefficient of Variation 14	376.5 L Geometric Coefficient of Variation 42	343.9 L Geometric Coefficient of Variation 36	—	—	—

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	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.	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.	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.	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.	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.	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.
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	142900 ng Geometric Coefficient of Variation 31	317900 ng Geometric Coefficient of Variation 41	404900 ng Geometric Coefficient of Variation 59	738300 ng Geometric Coefficient of Variation 40	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	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.	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.	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.	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.	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.	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.
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	0.1429 Percentage of PF-05251749 Geometric Coefficient of Variation 31	0.1591 Percentage of PF-05251749 Geometric Coefficient of Variation 41	0.1013 Percentage of PF-05251749 Geometric Coefficient of Variation 59	0.09849 Percentage of PF-05251749 Geometric Coefficient of Variation 41	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=8 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	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.	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.	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.	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.	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.	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.
Renal Clearance (CLr) of PF-05251749 - Day 14	37.18 mL/hr Geometric Coefficient of Variation 44	33.76 mL/hr Geometric Coefficient of Variation 33	37.39 mL/hr Geometric Coefficient of Variation 36	29.73 mL/hr Geometric Coefficient of Variation 30	22.15 mL/hr Geometric Coefficient of Variation 31	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=9 Participants 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.	PF-05251749 100 mg AM (Part A) n=10 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=6 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=7 Participants 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.	Placebo (Part B) n=12 Participants 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.	PF-05251749 50 mg PM (Part B) n=8 Participants 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.	PF-05251749 200 mg PM (Part B) n=8 Participants 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.	PF-05251749 500 mg PM (Part B) n=8 Participants 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.
Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 6	10.0 min Standard Deviation 45.17	3.3 min Standard Deviation 64.42	11.3 min Standard Deviation 45.18	37.5 min Standard Deviation 78.90	85.0 min Standard Deviation 83.61	124.3 min Standard Deviation 61.06	150.0 min Standard Deviation 56.12	13.6 min Standard Deviation 64.85	86.3 min Standard Deviation 84.00	135.0 min Standard Deviation 88.49	205.0 min Standard Deviation 44.16

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	PF-05251749 50 mg AM (Part A) n=9 Participants 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.	PF-05251749 100 mg AM (Part A) n=10 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 100 mg AM (Part A) n=6 Participants 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.	PF-05251749 200 mg AM (Part A) n=8 Participants 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.	PF-05251749 400 mg AM (Part A) n=8 Participants 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.	PF-05251749 750 mg AM (Part A) n=7 Participants 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.	Placebo (Part B) n=12 Participants 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.	PF-05251749 50 mg PM (Part B) n=8 Participants 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.	PF-05251749 200 mg PM (Part B) n=8 Participants 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.	PF-05251749 500 mg PM (Part B) n=8 Participants 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.
Change From Baseline for Dim Light Melatonin Onset (DLMO) Time - Day 15	40.0 min Standard Deviation 61.97	-36.7 min Standard Deviation 93.41	56.3 min Standard Deviation 54.23	112.5 min Standard Deviation 75.00	100.0 min Standard Deviation 137.70	115.7 min Standard Deviation 118.02	150.0 min Standard Deviation 56.12	49.1 min Standard Deviation 103.29	150.0 min Standard Deviation 73.48	135.0 min Standard Deviation 88.49	210.0 min Standard Deviation 47.43

Adverse Events

Placebo (Part A)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Melatonin 0.5 mg PM (Part A)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

PF-05251749 50 mg AM (Part A)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

PF-05251749 100 mg AM (Part A)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

PF-05251749 200 mg AM (Part A)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

PF-05251749 400 mg AM (Part A)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

PF-05251749 750 mg AM (Part A)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo (Part B)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

PF-05251749 50 mg PM (Part B)

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

PF-05251749 200 mg PM (Part B)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

PF-05251749 500 mg PM (Part B)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo (Part A) n=10 participants at risk 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.	Melatonin 0.5 mg PM (Part A) n=11 participants at risk 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.	PF-05251749 50 mg AM (Part A) n=8 participants at risk 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.	PF-05251749 100 mg AM (Part A) n=8 participants at risk 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.	PF-05251749 200 mg AM (Part A) n=8 participants at risk 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.	PF-05251749 400 mg AM (Part A) n=8 participants at risk 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.	PF-05251749 750 mg AM (Part A) n=8 participants at risk 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.	Placebo (Part B) n=12 participants at risk 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.	PF-05251749 50 mg PM (Part B) n=8 participants at risk 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.	PF-05251749 200 mg PM (Part B) n=8 participants at risk 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.	PF-05251749 500 mg PM (Part B) n=8 participants at risk 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.
Cardiac disorders Atrial fibrillation	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).

Other adverse events

Measure	Placebo (Part A) n=10 participants at risk 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.	Melatonin 0.5 mg PM (Part A) n=11 participants at risk 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.	PF-05251749 50 mg AM (Part A) n=8 participants at risk 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.	PF-05251749 100 mg AM (Part A) n=8 participants at risk 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.	PF-05251749 200 mg AM (Part A) n=8 participants at risk 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.	PF-05251749 400 mg AM (Part A) n=8 participants at risk 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.	PF-05251749 750 mg AM (Part A) n=8 participants at risk 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.	Placebo (Part B) n=12 participants at risk 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.	PF-05251749 50 mg PM (Part B) n=8 participants at risk 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.	PF-05251749 200 mg PM (Part B) n=8 participants at risk 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.	PF-05251749 500 mg PM (Part B) n=8 participants at risk 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.
Blood and lymphatic system disorders Thrombocytosis	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Gastrointestinal disorders Constipation	10.0% 1/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	25.0% 2/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	8.3% 1/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Gastrointestinal disorders Diarrhoea	10.0% 1/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	25.0% 2/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Gastrointestinal disorders Dyspepsia	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	8.3% 1/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Gastrointestinal disorders Frequent bowel movements	10.0% 1/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	37.5% 3/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Gastrointestinal disorders Nausea	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	50.0% 4/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	25.0% 2/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Gastrointestinal disorders Toothache	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
General disorders Chills	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Infections and infestations Pharyngitis	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Infections and infestations Upper respiratory tract infection	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	25.0% 2/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Infections and infestations Urinary tract infection	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Investigations Alanine aminotransferase increased	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	50.0% 4/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Investigations Blood creatine phosphokinase increased	10.0% 1/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	9.1% 1/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Investigations Electrocardiogram T wave inversion	10.0% 1/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Investigations Haemoglobin decreased	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Investigations Hepatic enzyme abnormal	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	25.0% 2/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Investigations Hepatic enzyme increased	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Investigations White blood cell count decreased	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	9.1% 1/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Nervous system disorders Dizziness	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	9.1% 1/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	50.0% 4/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	50.0% 4/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	50.0% 4/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Nervous system disorders Headache	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	9.1% 1/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	37.5% 3/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	8.3% 1/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	25.0% 2/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Nervous system disorders Presyncope	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Psychiatric disorders Insomnia	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	62.5% 5/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	87.5% 7/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Cardiac disorders Palpitations	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Renal and urinary disorders Haematuria	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Vascular disorders Hot flush	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	8.3% 1/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	75.0% 6/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Gastrointestinal disorders Vomiting	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	8.3% 1/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).
Metabolism and nutrition disorders Decreased appetite	0.00% 0/10 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/11 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/12 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	0.00% 0/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).	12.5% 1/8 • Day 1 to follow-up visit (28 calendar days after the last dose of investigational product on Day 14).

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER