Trial Outcomes & Findings for A Study To Examine Safety, Pharmacokinetics, And Pharmacodynamic Of Pf 06412562 In Subjects With Schizophrenia (NCT NCT02418819)

Last Updated: 2019-02-04

Results Overview

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. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Any events occurring following start of treatment or increasing in severity were counted as treatment emergent. AEs included both serious and non-serious AEs.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

103 participants

Primary outcome timeframe

Baseline up to 7-10 days after last dose of study drug, up to 26 days

Results posted on

2019-02-04

Participant Flow

A total of 103 participants were randomized and assigned to study treatment. One (1) participant in the PF-06412562 3 mg twice a day (BID) group and 2 participants in the PF-06412562 45 mg BID group did not receive study drug. Therefore, 100 participants received study treatment.

Participant milestones

Participant milestones
Measure	PF-06412562 3 mg BID Participant received 3 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 9 mg BID Participant received 9 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 45 mg BID Participant received 45 mg PF 06412562 modified release tablets were orally administered twice daily using a titration scheme (15 mg BID for 2 days, 30 mg BID for 2 days and 45 mg BID for the rest of the study) for 15 days with approximately 12 hours between each dose.	Placebo Participant received placebo matched to PF 06412562 3 mg and 15 mg modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.
Overall Study STARTED	22	16	33	29
Overall Study COMPLETED	21	16	29	28
Overall Study NOT COMPLETED	1	0	4	1

Reasons for withdrawal

Reasons for withdrawal
Measure	PF-06412562 3 mg BID Participant received 3 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 45 mg BID Participant received 45 mg PF 06412562 modified release tablets were orally administered twice daily using a titration scheme (15 mg BID for 2 days, 30 mg BID for 2 days and 45 mg BID for the rest of the study) for 15 days with approximately 12 hours between each dose.	Placebo Participant received placebo matched to PF 06412562 3 mg and 15 mg modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.
Overall Study Adverse Event	0	1	0
Overall Study Lost to Follow-up	1	0	0
Overall Study No longer meets eligibility criteria	0	1	0
Overall Study No longer willing to participate	0	2	1

Baseline Characteristics

A Study To Examine Safety, Pharmacokinetics, And Pharmacodynamic Of Pf 06412562 In Subjects With Schizophrenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PF-06412562 3 mg BID n=22 Participants Participant received 3 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 9 mg BID n=16 Participants Participant received 9 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 45 mg BID n=33 Participants Participant received 45 mg PF 06412562 modified release tablets were orally administered twice daily using a titration scheme (15 mg BID for 2 days, 30 mg BID for 2 days and 45 mg BID for the rest of the study) for 15 days with approximately 12 hours between each dose.	Placebo n=29 Participants Participant received placebo matched to PF 06412562 3 mg and 15 mg modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	Total n=100 Participants Total of all reporting groups
Age, Continuous	35.8 years STANDARD_DEVIATION 6.1 • n=5 Participants	34.3 years STANDARD_DEVIATION 7.2 • n=7 Participants	33.8 years STANDARD_DEVIATION 6.9 • n=5 Participants	35.7 years STANDARD_DEVIATION 5.8 • n=4 Participants	34.9 years STANDARD_DEVIATION 6.4 • n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants	9 Participants n=4 Participants	23 Participants n=21 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	13 Participants n=7 Participants	25 Participants n=5 Participants	20 Participants n=4 Participants	77 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline up to 7-10 days after last dose of study drug, up to 26 days

Population: The safety analysis set was used, defined as all participants who received at least 1 dose of study medication.

Outcome measures

Outcome measures
Measure	PF-06412562 3 mg BID n=22 Participants Participant received 3 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 9 mg BID n=16 Participants Participant received 9 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 45 mg BID n=33 Participants Participant received 45 mg PF 06412562 modified release tablets were orally administered twice daily using a titration scheme (15 mg BID for 2 days, 30 mg BID for 2 days and 45 mg BID for the rest of the study) for 15 days with approximately 12 hours between each dose.	Placebo n=29 Participants Participant received placebo matched to PF 06412562 3 mg and 15 mg modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) AEs	10 Participants	10 Participants	17 Participants	14 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) SAEs	1 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline up to 7-10 days after last dose of study drug, up to 26 days

Population: The safety analysis set was used, which defined as all participants who received at least 1 dose of study medication.

Vital Signs tests included systolic and diastolic blood pressure (BP) and pulse rate of seated supine and standing . Vital signs categorical summarization criteria were 1), supine and standing BP: systolic (SBP) greater than or equal to (\>=) 30 millimeters of mercury (mm Hg) change from baseline, systolic less than (\<) 90 mm Hg; diastolic BP (DBP) \>=20 mm Hg change from baseline, diastolic \<50 mm Hg; 2), supine and standing pulse rate \<40 or greater than (\>) 120 beats per minute (bpm).

Outcome measures

Outcome measures
Measure	PF-06412562 3 mg BID n=22 Participants Participant received 3 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 9 mg BID n=16 Participants Participant received 9 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 45 mg BID n=33 Participants Participant received 45 mg PF 06412562 modified release tablets were orally administered twice daily using a titration scheme (15 mg BID for 2 days, 30 mg BID for 2 days and 45 mg BID for the rest of the study) for 15 days with approximately 12 hours between each dose.	Placebo n=29 Participants Participant received placebo matched to PF 06412562 3 mg and 15 mg modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.
Number of Participants With Supine and Standing Vital Signs Meeting Categorical Summarization Criteria Supine Pulse rate <40 bpm	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Supine and Standing Vital Signs Meeting Categorical Summarization Criteria Supine SBP <90 mm Hg	1 Participants	3 Participants	6 Participants	6 Participants
Number of Participants With Supine and Standing Vital Signs Meeting Categorical Summarization Criteria Standing SBP <90 mm Hg	1 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Supine and Standing Vital Signs Meeting Categorical Summarization Criteria Supine DBP <50 mm Hg	0 Participants	2 Participants	2 Participants	2 Participants
Number of Participants With Supine and Standing Vital Signs Meeting Categorical Summarization Criteria Standing DBP <50 mm Hg	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Supine and Standing Vital Signs Meeting Categorical Summarization Criteria Supine Pulse rate >120 bpm	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Supine and Standing Vital Signs Meeting Categorical Summarization Criteria Standing Pulse rate <40 bpm	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Supine and Standing Vital Signs Meeting Categorical Summarization Criteria Standing Pulse rate >140 bpm	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Supine and Standing Vital Signs Meeting Categorical Summarization Criteria Increase: supine SBP >=30 mm Hg	3 Participants	4 Participants	4 Participants	1 Participants
Number of Participants With Supine and Standing Vital Signs Meeting Categorical Summarization Criteria Increase: standing SBP >=30 mm Hg	1 Participants	1 Participants	0 Participants	3 Participants
Number of Participants With Supine and Standing Vital Signs Meeting Categorical Summarization Criteria Increase: supine DBP >=20 mm Hg	1 Participants	4 Participants	1 Participants	1 Participants
Number of Participants With Supine and Standing Vital Signs Meeting Categorical Summarization Criteria Increase: standing DBP >=20 mm Hg	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Supine and Standing Vital Signs Meeting Categorical Summarization Criteria Decrease: supine SBP >= 30 mm Hg	1 Participants	3 Participants	4 Participants	3 Participants
Number of Participants With Supine and Standing Vital Signs Meeting Categorical Summarization Criteria Decrease: standing SBP >= 30 mm Hg	2 Participants	0 Participants	2 Participants	2 Participants
Number of Participants With Supine and Standing Vital Signs Meeting Categorical Summarization Criteria Decrease: supine DBP >=20 mm Hg	3 Participants	3 Participants	9 Participants	5 Participants
Number of Participants With Supine and Standing Vital Signs Meeting Categorical Summarization Criteria Decrease: standing DBP >=20 mm Hg	2 Participants	1 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline up to 7-10 days after last dose of study drug, up to 26 days

Population: The safety analysis set was used, defined as all participants who received at least 1 dose of study medication.

ECG categorical summarization criteria were 1), time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS interval): more than or equal to (\>=) 200 milliseconds (msec); for percent change(PChg), \>=25 percent (%) increase when baseline (b)\>100 msec; or increase \>=50% when b less than or equal to (\<=)100 msec; 2), the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization (PR interval): \>=300 msec; \>=25percent (%) increase when b \>200 msec; or increase \>=50% when b \<=200 msec; 3), time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula (QTcF interval): absolute value \>=450 - \<480 msec, \>=480-\<500 msec and \>=500 msec; increase from b \>=30 - \<60 and \>=60 msec

Outcome measures

Outcome measures
Measure	PF-06412562 3 mg BID n=22 Participants Participant received 3 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 9 mg BID n=16 Participants Participant received 9 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 45 mg BID n=33 Participants Participant received 45 mg PF 06412562 modified release tablets were orally administered twice daily using a titration scheme (15 mg BID for 2 days, 30 mg BID for 2 days and 45 mg BID for the rest of the study) for 15 days with approximately 12 hours between each dose.	Placebo n=29 Participants Participant received placebo matched to PF 06412562 3 mg and 15 mg modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.
Number of Participants With Electrocardiogram (ECG) (Standard 12-Lead) Data Meeting Categorical Summarization Criteria PR interval >=300 msec	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) (Standard 12-Lead) Data Meeting Categorical Summarization Criteria QRS complex >=200 msec	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) (Standard 12-Lead) Data Meeting Categorical Summarization Criteria QTcF interval 450-480 msec	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) (Standard 12-Lead) Data Meeting Categorical Summarization Criteria QTcF interval 480-500 msec	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) (Standard 12-Lead) Data Meeting Categorical Summarization Criteria QTcF interval >=500 msec	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) (Standard 12-Lead) Data Meeting Categorical Summarization Criteria PR interval increase b>200 & PChg>=25%	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) (Standard 12-Lead) Data Meeting Categorical Summarization Criteria PR interval increase b<=200 & PChg>=50%	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) (Standard 12-Lead) Data Meeting Categorical Summarization Criteria QRS complex increase b>100 & PChg>=25%	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) (Standard 12-Lead) Data Meeting Categorical Summarization Criteria QRS complex increase b<=100 & PChg>=50%	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) (Standard 12-Lead) Data Meeting Categorical Summarization Criteria QTcF interval increase 30-60 msec	3 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) (Standard 12-Lead) Data Meeting Categorical Summarization Criteria QTcF interval increase >=60 msec	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline up to Day 15

Population: The safety analysis set was used, defined as all participants who received at least 1 dose of study medication. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure.

The total number of participants with blood and urine laboratory test abnormalities (without regard to baseline abnormality) was assessed. Clinical laboratory tests included hematology, chemistry, urinalysis, and some other tests.

Outcome measures

Outcome measures
Measure	PF-06412562 3 mg BID n=22 Participants Participant received 3 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 9 mg BID n=16 Participants Participant received 9 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 45 mg BID n=29 Participants Participant received 45 mg PF 06412562 modified release tablets were orally administered twice daily using a titration scheme (15 mg BID for 2 days, 30 mg BID for 2 days and 45 mg BID for the rest of the study) for 15 days with approximately 12 hours between each dose.	Placebo n=28 Participants Participant received placebo matched to PF 06412562 3 mg and 15 mg modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.
Number of Participants With Blood and Urine Safety Laboratory Test Abnormalities	9 Participants	8 Participants	8 Participants	12 Participants

PRIMARY outcome

Timeframe: Baseline, Days 1,7 and follow-up (7-10 days after last dose of study drug, up to 26 days)

Population: The safety analysis set was used, defined as all participants who received at least 1 dose of study medication

The C-SSRS was an interview based rating scale to systematically assess suicidal ideation and suicidal behavior. Versions were available for Screening/Baseline and follow-up visits. Post-baseline suicidality was displayed without regard to baseline and as new onset or worsening relative to baseline. A participant was considered to have a new onset of suicidality if the participant reported no ideation and no behavior at the baseline assessment. A participant was considered to have a worsening of suicidality if the participant moved to a lower numbered Columbia Classification Algorithm of Suicide Assessment (C-CASA) category (observed in categories 1-4) than was reported at baseline.

Outcome measures

Outcome measures
Measure	PF-06412562 3 mg BID n=22 Participants Participant received 3 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 9 mg BID n=16 Participants Participant received 9 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 45 mg BID n=33 Participants Participant received 45 mg PF 06412562 modified release tablets were orally administered twice daily using a titration scheme (15 mg BID for 2 days, 30 mg BID for 2 days and 45 mg BID for the rest of the study) for 15 days with approximately 12 hours between each dose.	Placebo n=29 Participants Participant received placebo matched to PF 06412562 3 mg and 15 mg modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.
Number of Participants With New Onset and Worsening of Post Baseline Suicidality in Columbia Suicide Severity Rating Scale (C-SSRS) on Day 1, Day 7 and Follow-up. Day1 New Onset	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With New Onset and Worsening of Post Baseline Suicidality in Columbia Suicide Severity Rating Scale (C-SSRS) on Day 1, Day 7 and Follow-up. Day1 Worsening	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With New Onset and Worsening of Post Baseline Suicidality in Columbia Suicide Severity Rating Scale (C-SSRS) on Day 1, Day 7 and Follow-up. Day7 New Onset	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With New Onset and Worsening of Post Baseline Suicidality in Columbia Suicide Severity Rating Scale (C-SSRS) on Day 1, Day 7 and Follow-up. Day7 Worsening	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With New Onset and Worsening of Post Baseline Suicidality in Columbia Suicide Severity Rating Scale (C-SSRS) on Day 1, Day 7 and Follow-up. Follow Up New Onset	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With New Onset and Worsening of Post Baseline Suicidality in Columbia Suicide Severity Rating Scale (C-SSRS) on Day 1, Day 7 and Follow-up. Follow Up Worsening	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline, Day 13

Population: Per Protocol Analysis Set (PPAS)subset of Full Analysis Set(FAS).Criteria:1)Received all doses of study treatment to which they randomized2)No major protocol deviation3)Had baseline measurement and at least 1 post baseline measurement for at least 1 PD endpoint.Overall Number of Participants Analyzed=participants evaluable in this outcome measure.

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess working memory of participants. Total score range of this subset ranges from 40 (minimum score) to 60 (maximum score), with higher scores indicating better cognitive function.

Outcome measures

Outcome measures
Measure	PF-06412562 3 mg BID n=22 Participants Participant received 3 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 9 mg BID n=16 Participants Participant received 9 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 45 mg BID n=29 Participants Participant received 45 mg PF 06412562 modified release tablets were orally administered twice daily using a titration scheme (15 mg BID for 2 days, 30 mg BID for 2 days and 45 mg BID for the rest of the study) for 15 days with approximately 12 hours between each dose.	Placebo n=28 Participants Participant received placebo matched to PF 06412562 3 mg and 15 mg modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.
Change From Baseline to Day 13 of Wechsler Memory Scale (WMS III) Spatial Span + Letter Number Span Composite Score (Working Memory Domain)	3.95 Scores on a scale Standard Deviation 8.20	3.13 Scores on a scale Standard Deviation 7.90	1.28 Scores on a scale Standard Deviation 7.51	5.25 Scores on a scale Standard Deviation 6.96

PRIMARY outcome

Timeframe: Baseline, Day 15

Population: PPAS was used,defined as subset of FAS dataset.Criteria for PPAS:1)Received all doses of study treatment to which they were randomized;2)No major protocol deviation;3)Had a baseline measurement and at least 1 post baseline measurement for at least 1 PD endpoint.Overall Number of Participants Analyzed=participants evaluable in this outcome measure.

MRI parameter estimates refer to the 90th percentile Z-statistics across all voxels within the Region of Interest (ROI). This task provided a measure of reward anticipation and reward consummation. One of 3 shapes was presented on the screen (each uniquely associated with gain, loss and neutral) as a cue, and participants were instructed to respond to each cue, using their dominant hand, by pressing in response to a subsequent target that appeared for a variable length of time. Baseline was defined as Day 0 assessment. To be included in analysis participants must have complete Monetary Incentive Delay (MID) data at both Baseline and post-baseline, without excessive head motion. Participants with MID \<40% at baseline were excluded from the analysis and summary statistics. Scores were not bounded by a minimum or maximum range, higher z-score implies a greater motivation of the participant by the prospect of monetary gain than no monetary gain.

Outcome measures

Outcome measures
Measure	PF-06412562 3 mg BID n=13 Participants Participant received 3 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 9 mg BID n=15 Participants Participant received 9 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 45 mg BID n=24 Participants Participant received 45 mg PF 06412562 modified release tablets were orally administered twice daily using a titration scheme (15 mg BID for 2 days, 30 mg BID for 2 days and 45 mg BID for the rest of the study) for 15 days with approximately 12 hours between each dose.	Placebo n=25 Participants Participant received placebo matched to PF 06412562 3 mg and 15 mg modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.
Change From Baseline in Blood Oxygen Level Dependent (BOLD) fMRI Activation Parameter Estimates (Z-scores) in Anterior Ventral Striatum Region of Interest (ROI) for the Contrast of Cue Gain > Cue No Gain in Monetary Incentive Delay (MID) Task on Day 15	0.045 Z scores Standard Deviation 1.092	-0.229 Z scores Standard Deviation 1.042	0.075 Z scores Standard Deviation 1.139	-0.048 Z scores Standard Deviation 0.991

SECONDARY outcome

Timeframe: 6, and 12 hours on Days 1, 7 and 12, as well as 0 hours on Day 16

Population: The PK concentration analysis set was defined as all participants randomized and treated who had at least 1 PK concentration. Here, "number analyzed" signifies the participants evaluable for each time points.

PF-06412562 plasma concentration for each dose at 6 and 12 hours on Days 1, 7 and 12, as well as 0 hours on Day 16.

Outcome measures

Outcome measures
Measure	PF-06412562 3 mg BID n=22 Participants Participant received 3 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 9 mg BID n=16 Participants Participant received 9 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 45 mg BID n=33 Participants Participant received 45 mg PF 06412562 modified release tablets were orally administered twice daily using a titration scheme (15 mg BID for 2 days, 30 mg BID for 2 days and 45 mg BID for the rest of the study) for 15 days with approximately 12 hours between each dose.	Placebo Participant received placebo matched to PF 06412562 3 mg and 15 mg modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.
Plasma Concentrations of PF-06412562 for Each Dose. 6h on Day 1	19.99 ng/mL Standard Deviation 5.315	61.59 ng/mL Standard Deviation 26.366	100.9 ng/mL Standard Deviation 41.694	—
Plasma Concentrations of PF-06412562 for Each Dose. 12h on Day 1	16.14 ng/mL Standard Deviation 5.8686	47.88 ng/mL Standard Deviation 18.211	79.67 ng/mL Standard Deviation 37.939	—
Plasma Concentrations of PF-06412562 for Each Dose. 6h on Day 7	44.89 ng/mL Standard Deviation 34.585	113.8 ng/mL Standard Deviation 44.331	581.1 ng/mL Standard Deviation 309.63	—
Plasma Concentrations of PF-06412562 for Each Dose. 12h on Day 7	29.65 ng/mL Standard Deviation 24.259	72.59 ng/mL Standard Deviation 31.865	365.3 ng/mL Standard Deviation 179.43	—
Plasma Concentrations of PF-06412562 for Each Dose. 6h on Day 12	33.47 ng/mL Standard Deviation 10.815	92.39 ng/mL Standard Deviation 44.805	533.2 ng/mL Standard Deviation 298.43	—
Plasma Concentrations of PF-06412562 for Each Dose. 12h on Day 12	25.34 ng/mL Standard Deviation 12.383	67.34 ng/mL Standard Deviation 36.958	357.0 ng/mL Standard Deviation 160.09	—
Plasma Concentrations of PF-06412562 for Each Dose. 0h on Day 16	17.14 ng/mL Standard Deviation 24.418	24.96 ng/mL Standard Deviation 17.571	164.9 ng/mL Standard Deviation 105.95	—

SECONDARY outcome

Timeframe: 6 and 12 hours on Days 1, 7 and 12, as well as 0 hours on Day16

PF-06412562 plasma concentration for each dose at times 6 and 12 hours on Days 1, 7 and 12, as well as 0 hours on Day 16.

Outcome measures

Outcome measures
Measure	PF-06412562 3 mg BID n=22 Participants Participant received 3 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 9 mg BID n=16 Participants Participant received 9 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 45 mg BID n=33 Participants Participant received 45 mg PF 06412562 modified release tablets were orally administered twice daily using a titration scheme (15 mg BID for 2 days, 30 mg BID for 2 days and 45 mg BID for the rest of the study) for 15 days with approximately 12 hours between each dose.	Placebo Participant received placebo matched to PF 06412562 3 mg and 15 mg modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.
Plasma Concentrations of PF-06663872 at for Each Dose. 6h on Day 12	3.733 ng/mL Standard Deviation 1.1179	10.27 ng/mL Standard Deviation 4.9097	53.39 ng/mL Standard Deviation 24.715	—
Plasma Concentrations of PF-06663872 at for Each Dose. 6h on Day 1	1.707 ng/mL Standard Deviation 0.45216	5.649 ng/mL Standard Deviation 3.1174	8.894 ng/mL Standard Deviation 4.1986	—
Plasma Concentrations of PF-06663872 at for Each Dose. 12h on Day 1	1.948 ng/mL Standard Deviation 0.44567	5.355 ng/mL Standard Deviation 2.0234	8.108 ng/mL Standard Deviation 3.4277	—
Plasma Concentrations of PF-06663872 at for Each Dose. 6h on Day 7	5.289 ng/mL Standard Deviation 4.6182	12.00 ng/mL Standard Deviation 3.3004	58.36 ng/mL Standard Deviation 22.666	—
Plasma Concentrations of PF-06663872 at for Each Dose. 12h on Day 7	4.218 ng/mL Standard Deviation 4.9360	8.758 ng/mL Standard Deviation 3.3431	43.06 ng/mL Standard Deviation 16.824	—
Plasma Concentrations of PF-06663872 at for Each Dose. 12h on Day 12	3.144 ng/mL Standard Deviation 0.95169	8.604 ng/mL Standard Deviation 4.2130	40.95 ng/mL Standard Deviation 14.892	—
Plasma Concentrations of PF-06663872 at for Each Dose. 0h on Day 16	2.925 ng/mL Standard Deviation 4.8908	3.432 ng/mL Standard Deviation 2.1968	19.25 ng/mL Standard Deviation 9.0442	—

Adverse Events

PF-06412562 3 mg BID

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

PF-06412562 9 mg BID

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

PF-06412562 45 mg BID

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PF-06412562 3 mg BID n=22 participants at risk Participant received 3 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 9 mg BID n=16 participants at risk Participant received 9 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 45 mg BID n=33 participants at risk Participant received 45 mg PF 06412562 modified release tablets were orally administered twice daily using a titration scheme (15 mg BID for 2 days, 30 mg BID for 2 days and 45 mg BID for the rest of the study) for 15 days with approximately 12 hours between each dose.	Placebo n=29 participants at risk Participant received placebo matched to PF 06412562 3 mg and 15 mg modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.
Psychiatric disorders Psychotic disorder	4.5% 1/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Measure	PF-06412562 3 mg BID n=22 participants at risk Participant received 3 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 9 mg BID n=16 participants at risk Participant received 9 mg PF 06412562 modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.	PF-06412562 45 mg BID n=33 participants at risk Participant received 45 mg PF 06412562 modified release tablets were orally administered twice daily using a titration scheme (15 mg BID for 2 days, 30 mg BID for 2 days and 45 mg BID for the rest of the study) for 15 days with approximately 12 hours between each dose.	Placebo n=29 participants at risk Participant received placebo matched to PF 06412562 3 mg and 15 mg modified release tablets were orally administered twice daily for 15 days with approximately 12 hours between each dose.
Nervous system disorders Akathisia	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	6.2% 1/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	3.0% 1/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Nervous system disorders Dizziness	13.6% 3/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	9.1% 3/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Nervous system disorders Extrapyramidal disorder	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	6.2% 1/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Nervous system disorders Headache	18.2% 4/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	12.5% 2/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	24.2% 8/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	3.4% 1/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Nervous system disorders Sedation	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	6.1% 2/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Nervous system disorders Somnolence	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	3.0% 1/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	13.8% 4/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Psychiatric disorders Abnormal dreams	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	18.8% 3/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	9.1% 3/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Psychiatric disorders Insomnia	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	6.2% 1/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	3.0% 1/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	3.4% 1/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Psychiatric disorders Libido decreased	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	6.2% 1/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Psychiatric disorders Nightmare	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	6.2% 1/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Psychiatric disorders Psychotic disorder	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	6.2% 1/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	3.0% 1/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Psychiatric disorders Restlessness	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	10.3% 3/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Gastrointestinal disorders Abdominal discomfort	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	9.1% 3/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	3.4% 1/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Gastrointestinal disorders Constipation	4.5% 1/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	6.2% 1/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	3.0% 1/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Gastrointestinal disorders Diarrhoea	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	12.5% 2/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Gastrointestinal disorders Nausea	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	6.2% 1/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	15.2% 5/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Gastrointestinal disorders Toothache	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	6.2% 1/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Gastrointestinal disorders Vomiting	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	9.1% 3/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
General disorders Chest discomfort	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	6.1% 2/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Immune system disorders Hypersensitivity	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	6.2% 1/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Renal and urinary disorders Pollakiuria	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	6.2% 1/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Reproductive system and breast disorders Erectile dysfunction	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	6.2% 1/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	6.2% 1/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	6.1% 2/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	3.4% 1/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.5% 1/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	6.9% 2/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Skin and subcutaneous tissue disorders Blister	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	6.2% 1/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Skin and subcutaneous tissue disorders Rash	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	6.2% 1/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days
Skin and subcutaneous tissue disorders Skin irritation	0.00% 0/22 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	6.2% 1/16 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/33 • Baseline up to 7-10 days after last dose of study drug, up to 26 days	0.00% 0/29 • Baseline up to 7-10 days after last dose of study drug, up to 26 days