Trial Outcomes & Findings for Multiple Ascending Doses of PF-04958242 in Subjects With Stable Schizophrenia (NCT NCT02332798)

NCT ID: NCT02332798

Last Updated: 2021-10-25

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 39 participants
• Primary outcome timeframe: Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, and 12 hours post-dose)
• Results posted on: 2021-10-25

Participant Flow

Participant milestones

Measure	PF-04958242 0.25 mg All participants who received PF-04958242 0.25 milligram (mg) twice daily (BID) for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Overall Study STARTED	13	14	12
Overall Study COMPLETED	12	12	11
Overall Study NOT COMPLETED	1	2	1

Reasons for withdrawal

Measure	PF-04958242 0.25 mg All participants who received PF-04958242 0.25 milligram (mg) twice daily (BID) for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Overall Study Unwilling to Participate in Study	0	1	1
Overall Study Positive Urine Drug Test	0	1	0
Overall Study Abnormal Laboratory Findings	1	0	0

Baseline Characteristics

Multiple Ascending Doses of PF-04958242 in Subjects With Stable Schizophrenia

Baseline characteristics by cohort

Measure	PF-04958242 0.25 mg n=13 Participants All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=14 Participants All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo n=12 Participants All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Total n=39 Participants Total of all reporting groups
Age, Continuous	45.6 years STANDARD_DEVIATION 5.9 • n=5 Participants	41.6 years STANDARD_DEVIATION 7.5 • n=7 Participants	45.8 years STANDARD_DEVIATION 10.5 • n=5 Participants	44.3 years STANDARD_DEVIATION 8.1 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	11 Participants n=7 Participants	10 Participants n=5 Participants	34 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, and 12 hours post-dose)

Population: The pharmacokinetic (PK) concentration population is defined as all enrolled subjects treated who received at least one dose of PF-04958242 and have at least 1 measureable concentration.

Outcome measures

Measure	PF-04958242 0.25 mg n=13 Participants All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=14 Participants All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Maximum Observed Plasma Concentration (Cmax) (Single Dose)	1.920 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 23	3.830 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 21	—

PRIMARY outcome

Timeframe: Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12 hours post-dose), Day 2, Day 7 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 hours post-dose), Day 8, Day 10, Day 14 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 hours post-dose), Day 15, Day 17, Day 21

Population: The PK concentration population is defined as all enrolled subjects treated who received at least one dose of PF-04958242 and have at least 1 measureable concentration.

Cmax steady state for PF-04958242 0.25 mg group and PF-04958242 0.475 mg group at Day 14 were presented.

Outcome measures

Measure	PF-04958242 0.25 mg n=12 Participants All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=12 Participants All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Cmax (Steady State)	3.174 ng/mL Geometric Coefficient of Variation 18	7.139 ng/mL Geometric Coefficient of Variation 37	—

PRIMARY outcome

Timeframe: Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, and 12 hours post-dose)

Population: The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters interest measured.

Outcome measures

Measure	PF-04958242 0.25 mg n=13 Participants All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=14 Participants All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Time for Cmax (Tmax) (Single Dose)	1.65 hours Interval 1.0 to 2.0	1.33 hours Interval 0.167 to 3.0	—

PRIMARY outcome

Timeframe: Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12 hours post-dose), Day 2, Day 7 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 hours post-dose), Day 8, Day 10, Day 14 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 hours post-dose), Day 15, Day 17, Day 21

Population: The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters interest measured.

Tmax steady state for PF-04958242 0.25 mg group and PF-04958242 0.475 mg group at Day 14 were presented.

Outcome measures

Measure	PF-04958242 0.25 mg n=12 Participants All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=12 Participants All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Tmax (Steady State)	1.65 hours Interval 1.0 to 2.0	1.33 hours Interval 0.5 to 4.0	—

PRIMARY outcome

Timeframe: Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, and 12 hours post-dose)

Population: The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters interest measured.

Outcome measures

Measure	PF-04958242 0.25 mg n=13 Participants All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=14 Participants All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Area Under the Concentration-Time Profile From Time 0 to Time Tau (τ), the Dosing Interval, Where τ = 12 Hours (AUCτ) (Single Dose)	9.570 nanograms*hours per milliliter (ng*h/mL) Geometric Coefficient of Variation 19	17.72 nanograms*hours per milliliter (ng*h/mL) Geometric Coefficient of Variation 18	—

PRIMARY outcome

Timeframe: Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12 hours post-dose), Day 2, Day 7 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 hours post-dose), Day 8, Day 10, Day 14 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 hours post-dose), Day 15, Day 17, Day 21

Population: The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters interest measured.

AUCτ steady state for PF-04958242 0.25 mg group and PF-04958242 0.475 mg group at Day 14 were presented.

Outcome measures

Measure	PF-04958242 0.25 mg n=12 Participants All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=12 Participants All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
AUCτ (Steady State)	24.57 ng*h/mL Geometric Coefficient of Variation 19	50.09 ng*h/mL Geometric Coefficient of Variation 34	—

PRIMARY outcome

Timeframe: Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12 hours post-dose), Day 2, Day 7 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 hours post-dose), Day 8, Day 10, Day 14 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 hours post-dose), Day 15, Day 17, Day 21

Population: The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters interest measured.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F steady state for PF-04958242 0.25 mg group and PF-04958242 0.475 mg group at Day 14 were presented.

Outcome measures

Measure	PF-04958242 0.25 mg n=12 Participants All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=12 Participants All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Apparent Oral Clearance (CL/F) (Steady State)	169.5 milliliter per minute (mL/min) Geometric Coefficient of Variation 18	157.9 milliliter per minute (mL/min) Geometric Coefficient of Variation 34	—

PRIMARY outcome

Timeframe: Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12 hours post-dose), Day 2, Day 7 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 hours post-dose), Day 8, Day 10, Day 14 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 hours post-dose), Day 15, Day 17, Day 21

Population: The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters interest measured.

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. Vz/F steady state for PF-04958242 0.25 mg group and PF-04958242 0.475 mg group at Day 14 were presented.

Outcome measures

Measure	PF-04958242 0.25 mg n=12 Participants All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=12 Participants All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Apparent Volume of Distribution (Vz/F) (Steady State)	545.7 Liter (L) Geometric Coefficient of Variation 31	530.2 Liter (L) Geometric Coefficient of Variation 26	—

PRIMARY outcome

Timeframe: Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12 hours post-dose), Day 2, Day 7 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 hours post-dose), Day 8, Day 10, Day 14 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 hours post-dose), Day 15, Day 17, Day 21

Population: The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters interest measured.

Terminal half-life is the time measured for the plasma concentration to decrease by one half. t1/2 steady state for PF-04958242 0.25 mg group and PF-04958242 0.475 mg group at Day 14 were presented.

Outcome measures

Measure	PF-04958242 0.25 mg n=12 Participants All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=12 Participants All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Terminal Half-Life (t1/2) (Steady State)	39.64 hours Standard Deviation 14.878	42.18 hours Standard Deviation 14.421	—

PRIMARY outcome

Timeframe: Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12 hours post-dose), Day 2, Day 7 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 hours post-dose), Day 8, Day 10, Day 14 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 hours post-dose), Day 15, Day 17, Day 21

Population: The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters interest measured.

Accumulation ratio was calculated as, Rac obtained from Area Under the Concentration Time Curve (AUC) from time 0-t (Day X) divided by AUC from time 0-t (Day 1). Rac steady state for PF-04958242 0.25 mg group and PF-04958242 0.475 mg group at Day 14 (ie. X = 14) were presented.

Outcome measures

Measure	PF-04958242 0.25 mg n=12 Participants All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=12 Participants All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Observed Accumulation Ratio (Rac) (Steady State)	2.524 Ratio Geometric Coefficient of Variation 20	2.815 Ratio Geometric Coefficient of Variation 31	—

PRIMARY outcome

Timeframe: Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12 hours post-dose), Day 2, Day 7 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 hours post-dose), Day 8, Day 10, Day 14 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 hours post-dose), Day 15, Day 17, Day 21

Population: The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters interest measured.

Accumulation ratio based on Cmax was calculated as: Rac,Cmax = Cmax at steady state (ss) divided by Cmax at first dose. Rac, Cmax steady state for PF-04958242 0.25 mg group and PF-04958242 0.475 mg group at Day 14 were presented.

Outcome measures

Measure	PF-04958242 0.25 mg n=12 Participants All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=12 Participants All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Observed Accumulation Ratio for Cmax (Rac, Cmax) (Steady State)	1.645 Ratio Geometric Coefficient of Variation 23	1.797 Ratio Geometric Coefficient of Variation 51	—

PRIMARY outcome

Timeframe: Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12 hours post-dose), Day 2, Day 7 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 hours post-dose), Day 8, Day 10, Day 14 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 hours post-dose), Day 15, Day 17, Day 21

Population: The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters interest measured.

PTR was calculated as Cmax divided by Cmin (that is defined as lowest concentration observed during the dosing interval). PTR steady state for PF-04958242 0.25 mg group and PF-04958242 0.475 mg group at Day 14 were presented.

Outcome measures

Measure	PF-04958242 0.25 mg n=12 Participants All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=12 Participants All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Peak-to-Trough Ratio at Steady State (PTR)	2.323 Ratio Geometric Coefficient of Variation 19	2.531 Ratio Geometric Coefficient of Variation 28	—

PRIMARY outcome

Timeframe: Baseline up to Day 21

Population: The safety analysis population included all participants who received at least 1 dose of the study medication.

The following laboratory parameters were reported: hematology (hemoglobin, hematocrit, red blood cell [RBC] count, mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC], platelet count, white blood cell [WBC] count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen [BUN], creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, alkaline phosphatase, phosphorus, cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), bicarbonate, uric acid, albumin, and total protein); urinalysis (color, appearance, specific gravity, pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, and microscopy); others (follicle stimulating hormone [FSH], and urine drug screening).

Outcome measures

Measure	PF-04958242 0.25 mg n=13 Participants All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=14 Participants All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo n=12 Participants All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Number of Participants With Abnormal Clinical Laboratory Measurements	4 participants	4 participants	7 participants

PRIMARY outcome

Timeframe: Baseline up to Day 21

Population: The safety analysis population included all participants who received at least 1 dose of the study medication.

Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine/sitting pulse rate less than (<) 40 or greater than (>) 120 beats per minute (bpm), standing pulse rate <40 or >140 bpm; systolic blood pressure (SBP) greater than or equal to (>=) 30 millimeters of mercury (mm Hg) change from baseline in same posture or SBP <90 mm Hg, diastolic blood pressure (DBP) >=20 mm Hg change from baseline in same posture or DBP <50 mm Hg. IFB = increase from baseline; DFB = decrease from baseline.

Outcome measures

Measure	PF-04958242 0.25 mg n=13 Participants All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=14 Participants All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo n=12 Participants All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern Supine SBP <90 mmHg	0 participants	2 participants	0 participants
Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern Standing SBP <90 mmHg	0 participants	1 participants	0 participants
Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern Supine SBP >=30 mmHg IFB	0 participants	0 participants	1 participants
Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern Standing SBP >=30 mmHg IFB	2 participants	1 participants	1 participants
Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern Supine DBP >=20 mmHg IFB	0 participants	2 participants	1 participants
Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern Standing DBP >=20 mmHg IFB	2 participants	2 participants	0 participants
Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern Supine SBP >=30 mmHg DFB	2 participants	1 participants	0 participants
Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern Standing SBP >=30 mmHg DFB	2 participants	1 participants	1 participants
Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern Supine DBP >=20 mmHg DFB	2 participants	0 participants	3 participants
Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern Standing DBP >=20 mmHg DFB	5 participants	2 participants	4 participants

PRIMARY outcome

Timeframe: Baseline up to Day 21

Population: The safety analysis population included all participants who received at least 1 dose of the study medication.

Electrocardiogram (ECG) parameters included beginning of the P wave until the beginning of the QRS complex (PR) interval, time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS) interval, and QTc using Fridericia's formula (QTcF). Criteria for ECG changes meeting potential clinical concern included: PR interval >=300 milliseconds (msec) or >=25% increase when baseline is >200 msec and >=50% increase when baseline is less than or equal to (=<)200 msec; QRS interval >=140 msec or >=50% increase from baseline (IFB); and and QTcF >=450 to <480, 480 to <500 and >=500 msec. The number of participants with potentially clinically significant ECG findings at any visit were reported.

Outcome measures

Measure	PF-04958242 0.25 mg n=13 Participants All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=14 Participants All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo n=12 Participants All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Number of Participants With Electrocardiogram Data Meeting Criteria of Potential Clinical Concern	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Baseline up to Day 21

Population: The safety analysis population included all participants who received at least 1 dose of the study medication.

The extended neurological examination, performed by a board certified neurologist, included observation for cerebellar (intention) tremor and for non-cerebellar tremors (eg, resting or positional), finger, nose, heel, shin, Romberg, tandem walking, positional and gaze evoked nystagmus, reflexes, muscle strength, cranial nerves, sensory function of upper and lower extremities. The brief neurological examination included an assessment of motor and sensory function, cranial nerves, reflexes, non-cerebellar tremor (eg, resting or positional) and cerebellar function. The assessment of cerebellar function were complemented by the Scale for Assessment and Rating of Ataxia (SARA).

Outcome measures

Measure	PF-04958242 0.25 mg n=13 Participants All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=14 Participants All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo n=12 Participants All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Number of Participants With Abnormalities in Neurological Examination	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Baseline up to Day 21

Population: The safety analysis population included all participants who received at least 1 dose of the study medication.

A full physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The brief physical examination focused on general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms.

Outcome measures

Measure	PF-04958242 0.25 mg n=13 Participants All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=14 Participants All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo n=12 Participants All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Number of Participants With Abnormalities in Physical Examination	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Baseline up to 28 days after last study drug administration

Population: The safety analysis population included all participants who received at least 1 dose of the study medication.

An AE was any untoward medical occurrence in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.

Outcome measures

Measure	PF-04958242 0.25 mg n=13 Participants All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=14 Participants All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo n=12 Participants All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	10 participants	9 participants	4 participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Baseline up to Day 21

Population: The safety analysis population included all participants who received at least 1 dose of the study medication.

The C-SSRS (mapped to Columbia Classification Algorithm of Suicide Assessment [C-CASA]) is an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced the following: completed suicide (1), suicide attempt (2) (response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior (3)("Yes" on "preparatory acts or behavior"), suicidal ideation (4) ("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), any suicidal behavior or ideation, self-injurious behavior (7)("Yes" on "Has participant engaged in non-suicidal self-injurious behavior").

Outcome measures

Measure	PF-04958242 0.25 mg n=13 Participants All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=14 Participants All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo n=12 Participants All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Number of Participants With Positive Response to Columbia-Suicide Severity Rating Scale (C-SSRS)	0 participants	0 participants	0 participants

Adverse Events

PF-04958242 0.25 mg

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

PF-04958242 0.475 mg

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	PF-04958242 0.25 mg n=13 participants at risk All participants who received PF-04958242 0.25 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	PF-04958242 0.475 mg n=14 participants at risk All participants who received PF-04958242 0.475 mg BID for 14 consecutive days with the last dose occurring in the morning on Day 14.	Placebo n=12 participants at risk All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14.
Ear and labyrinth disorders Tinnitus	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	0.00% 0/14 • Baseline up to 28 days after last study drug administration.	8.3% 1/12 • Baseline up to 28 days after last study drug administration.
Eye disorders Eye pain	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	7.1% 1/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
Gastrointestinal disorders Abdominal pain	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	14.3% 2/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
Gastrointestinal disorders Constipation	7.7% 1/13 • Baseline up to 28 days after last study drug administration.	14.3% 2/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
Gastrointestinal disorders Diarrhoea	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	7.1% 1/14 • Baseline up to 28 days after last study drug administration.	8.3% 1/12 • Baseline up to 28 days after last study drug administration.
Gastrointestinal disorders Dry mouth	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	0.00% 0/14 • Baseline up to 28 days after last study drug administration.	8.3% 1/12 • Baseline up to 28 days after last study drug administration.
Gastrointestinal disorders Dyspepsia	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	7.1% 1/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
Gastrointestinal disorders Flatulence	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	0.00% 0/14 • Baseline up to 28 days after last study drug administration.	8.3% 1/12 • Baseline up to 28 days after last study drug administration.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	7.1% 1/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
Gastrointestinal disorders Nausea	7.7% 1/13 • Baseline up to 28 days after last study drug administration.	28.6% 4/14 • Baseline up to 28 days after last study drug administration.	8.3% 1/12 • Baseline up to 28 days after last study drug administration.
Gastrointestinal disorders Vomiting	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	21.4% 3/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
General disorders Nodule	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	7.1% 1/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
General disorders Oedema peripheral	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	0.00% 0/14 • Baseline up to 28 days after last study drug administration.	8.3% 1/12 • Baseline up to 28 days after last study drug administration.
General disorders Pain	7.7% 1/13 • Baseline up to 28 days after last study drug administration.	0.00% 0/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
Infections and infestations Folliculitis	7.7% 1/13 • Baseline up to 28 days after last study drug administration.	0.00% 0/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
Infections and infestations Upper respiratory tract infection	23.1% 3/13 • Baseline up to 28 days after last study drug administration.	0.00% 0/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
Injury, poisoning and procedural complications Fall	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	7.1% 1/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
Injury, poisoning and procedural complications Muscle strain	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	7.1% 1/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
Musculoskeletal and connective tissue disorders Muscle spasms	7.7% 1/13 • Baseline up to 28 days after last study drug administration.	0.00% 0/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
Musculoskeletal and connective tissue disorders Muscle tightness	7.7% 1/13 • Baseline up to 28 days after last study drug administration.	0.00% 0/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	7.7% 1/13 • Baseline up to 28 days after last study drug administration.	0.00% 0/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	7.1% 1/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	0.00% 0/14 • Baseline up to 28 days after last study drug administration.	8.3% 1/12 • Baseline up to 28 days after last study drug administration.
Nervous system disorders Dizziness	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	7.1% 1/14 • Baseline up to 28 days after last study drug administration.	16.7% 2/12 • Baseline up to 28 days after last study drug administration.
Nervous system disorders Headache	30.8% 4/13 • Baseline up to 28 days after last study drug administration.	28.6% 4/14 • Baseline up to 28 days after last study drug administration.	16.7% 2/12 • Baseline up to 28 days after last study drug administration.
Nervous system disorders Somnolence	23.1% 3/13 • Baseline up to 28 days after last study drug administration.	14.3% 2/14 • Baseline up to 28 days after last study drug administration.	16.7% 2/12 • Baseline up to 28 days after last study drug administration.
Nervous system disorders Tremor	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	7.1% 1/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
Psychiatric disorders Abnormal dreams	7.7% 1/13 • Baseline up to 28 days after last study drug administration.	7.1% 1/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
Psychiatric disorders Anxiety	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	7.1% 1/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
Psychiatric disorders Insomnia	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	7.1% 1/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
Psychiatric disorders Nightmare	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	7.1% 1/14 • Baseline up to 28 days after last study drug administration.	0.00% 0/12 • Baseline up to 28 days after last study drug administration.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	0.00% 0/14 • Baseline up to 28 days after last study drug administration.	8.3% 1/12 • Baseline up to 28 days after last study drug administration.
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/13 • Baseline up to 28 days after last study drug administration.	0.00% 0/14 • Baseline up to 28 days after last study drug administration.	8.3% 1/12 • Baseline up to 28 days after last study drug administration.

Additional Information

Biogen Study Medical Director

Biogen

Phone: 866-633-4636

Email: clinicaltrials@biogen.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