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| ID | Type | Description | Link |
|---|---|---|---|
| MAD | Other Identifier | Alias Study Number |
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This study aims to assess the safety, tolerability and pharmacokinetics of PF-04958242 in multiple ascending doses in subjects with stable schizophrenia.
This study aims to assess the safety, tolerability and pharmacokinetics of PF-04958242 compared to placebo over 14 days twice a day dosing in multiple ascending doses in subjects with stable schizophrenia.
This study was previously posted by Pfizer, Inc. Sponsorship of the trial was transferred to Biogen.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PF-04958242 0.25 mg | Experimental | 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 | Experimental | 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. |
|
| Matching Placebo | Placebo Comparator | All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-04958242 | Drug | Administered as specified in the treatment arm |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) (Single Dose) | Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, and 12 hours post-dose) | |
| Cmax (Steady State) | Cmax steady state for PF-04958242 0.25 mg group and PF-04958242 0.475 mg group at Day 14 were presented. | 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 |
| Time for Cmax (Tmax) (Single Dose) | Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, and 12 hours post-dose) | |
| Tmax (Steady State) | Tmax steady state for PF-04958242 0.25 mg group and PF-04958242 0.475 mg group at Day 14 were presented. | 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 |
| Area Under the Concentration-Time Profile From Time 0 to Time Tau (Ï„), the Dosing Interval, Where Ï„ = 12 Hours (AUCÏ„) (Single Dose) | Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, and 12 hours post-dose) | |
| AUCÏ„ (Steady State) | AUCÏ„ steady state for PF-04958242 0.25 mg group and PF-04958242 0.475 mg group at Day 14 were presented. | 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 |
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Key Inclusion Criteria:
Key Exclusion Criteria:
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Biogen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Collaborative Neuroscience Network, LLC. | Long Beach | California | 90806 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | Placebo | All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | PF-04958242 0.25 mg | 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. |
| BG001 | PF-04958242 0.475 mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Observed Plasma Concentration (Cmax) (Single Dose) | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, and 12 hours post-dose) |
|
Baseline up to 28 days after last study drug administration.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PF-04958242 0.25 mg | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tinnitus | Ear and labyrinth disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Biogen Study Medical Director | Biogen | 866-633-4636 | clinicaltrials@biogen.com |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C000600968 | PF-04958242 |
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| Placebo | Drug | Administered as specified in the treatment arm |
|
| Apparent Oral Clearance (CL/F) (Steady State) | 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. | 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 |
| Apparent Volume of Distribution (Vz/F) (Steady State) | 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. | 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 |
| Terminal Half-Life (t1/2) (Steady State) | 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. | 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 |
| Observed Accumulation Ratio (Rac) (Steady State) | 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. | 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 |
| Observed Accumulation Ratio for Cmax (Rac, Cmax) (Steady State) | 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. | 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 |
| Peak-to-Trough Ratio at Steady State (PTR) | 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. | 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 |
| Number of Participants With Abnormal Clinical Laboratory Measurements | 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). | Baseline up to Day 21 |
| Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern | 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. | Baseline up to Day 21 |
| Number of Participants With Electrocardiogram Data Meeting Criteria of Potential Clinical Concern | 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. | Baseline up to Day 21 |
| Number of Participants With Abnormalities in Neurological Examination | 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). | Baseline up to Day 21 |
| Number of Participants With Abnormalities in Physical Examination | 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. | Baseline up to Day 21 |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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. | Baseline up to 28 days after last study drug administration |
| Number of Participants With Positive Response to Columbia-Suicide Severity Rating Scale (C-SSRS) | 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"). | Baseline up to Day 21 |
| Abnormal Laboratory Findings |
|
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.
| BG002 | Placebo | All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
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|
| Primary | Cmax (Steady State) | Cmax steady state for PF-04958242 0.25 mg group and PF-04958242 0.475 mg group at Day 14 were presented. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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 |
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| Primary | Time for Cmax (Tmax) (Single Dose) | The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters interest measured. | Posted | Median | Full Range | hours | Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, and 12 hours post-dose) |
|
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| Primary | Tmax (Steady State) | Tmax steady state for PF-04958242 0.25 mg group and PF-04958242 0.475 mg group at Day 14 were presented. | The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters interest measured. | Posted | Median | Full Range | hours | 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 |
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| Primary | Area Under the Concentration-Time Profile From Time 0 to Time Tau (Ï„), the Dosing Interval, Where Ï„ = 12 Hours (AUCÏ„) (Single Dose) | The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters interest measured. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms*hours per milliliter (ng*h/mL) | Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, and 12 hours post-dose) |
|
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| Primary | AUCÏ„ (Steady State) | AUCÏ„ steady state for PF-04958242 0.25 mg group and PF-04958242 0.475 mg group at Day 14 were presented. | The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters interest measured. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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 |
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| Primary | Apparent Oral Clearance (CL/F) (Steady State) | 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. | The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters interest measured. | Posted | Geometric Mean | Geometric Coefficient of Variation | milliliter per minute (mL/min) | 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 |
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| Primary | Apparent Volume of Distribution (Vz/F) (Steady State) | 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. | The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters interest measured. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter (L) | 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 |
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| Primary | Terminal Half-Life (t1/2) (Steady State) | 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. | The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters interest measured. | Posted | Mean | Standard Deviation | hours | 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 |
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| Primary | Observed Accumulation Ratio (Rac) (Steady State) | 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. | The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters interest measured. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | 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 |
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| Primary | Observed Accumulation Ratio for Cmax (Rac, Cmax) (Steady State) | 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. | The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters interest measured. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | 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 |
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| Primary | Peak-to-Trough Ratio at Steady State (PTR) | 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. | The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters interest measured. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | 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 |
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| Primary | Number of Participants With Abnormal Clinical Laboratory Measurements | 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). | The safety analysis population included all participants who received at least 1 dose of the study medication. | Posted | Number | participants | Baseline up to Day 21 |
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| Primary | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern | 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. | The safety analysis population included all participants who received at least 1 dose of the study medication. | Posted | Number | participants | Baseline up to Day 21 |
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| Primary | Number of Participants With Electrocardiogram Data Meeting Criteria of Potential Clinical Concern | 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. | The safety analysis population included all participants who received at least 1 dose of the study medication. | Posted | Number | participants | Baseline up to Day 21 |
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| Primary | Number of Participants With Abnormalities in Neurological Examination | 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). | The safety analysis population included all participants who received at least 1 dose of the study medication. | Posted | Number | participants | Baseline up to Day 21 |
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| Primary | Number of Participants With Abnormalities in Physical Examination | 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. | The safety analysis population included all participants who received at least 1 dose of the study medication. | Posted | Number | participants | Baseline up to Day 21 |
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| Primary | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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. | The safety analysis population included all participants who received at least 1 dose of the study medication. | Posted | Number | participants | Baseline up to 28 days after last study drug administration |
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| Primary | Number of Participants With Positive Response to Columbia-Suicide Severity Rating Scale (C-SSRS) | 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"). | The safety analysis population included all participants who received at least 1 dose of the study medication. | Posted | Number | participants | Baseline up to Day 21 |
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| 0 |
| 13 |
| 10 |
| 13 |
| EG001 | 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. | 0 | 14 | 9 | 14 |
| EG002 | Placebo | All participants who received placebo BID for 14 consecutive days with the last dose occurring in the morning on Day 14. | 0 | 12 | 4 | 12 |
| Eye pain | Eye disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Nodule | General disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Pain | General disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Folliculitis | Infections and infestations | MedDRA 18.0 | Non-systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 18.0 | Non-systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA 18.0 | Non-systematic Assessment |
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| Muscle strain | Injury, poisoning and procedural complications | MedDRA 18.0 | Non-systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Muscle tightness | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Abnormal dreams | Psychiatric disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Nightmare | Psychiatric disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Eczema | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
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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.
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| Supine SBP >=30 mmHg IFB |
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| Standing SBP >=30 mmHg IFB |
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| Supine DBP >=20 mmHg IFB |
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| Standing DBP >=20 mmHg IFB |
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| Supine SBP >=30 mmHg DFB |
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| Standing SBP >=30 mmHg DFB |
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| Supine DBP >=20 mmHg DFB |
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| Standing DBP >=20 mmHg DFB |
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| Title | Measurements |
|---|---|
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