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Trial record 1 of 1 for:    NCT02332798
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Multiple Ascending Doses of PF-04958242 in Subjects With Stable Schizophrenia (MAD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02332798
Recruitment Status : Completed
First Posted : January 7, 2015
Results First Posted : June 14, 2016
Last Update Posted : January 9, 2020
Sponsor:
Information provided by (Responsible Party):
Biogen

Brief Summary:
This study aims to assess the safety, tolerability and pharmacokinetics of PF-04958242 in multiple ascending doses in subjects with stable schizophrenia.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: PF-04958242 Drug: Placebo Phase 1

Detailed Description:

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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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 39 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo Controlled, Sponsor Open, Parallel Group Phase 1b Study To Examine The Safety, Tolerability And Pharmacokinetics Of Multiple Ascending Doses Of Pf-04958242 In Subjects With Stable Schizophrenia
Actual Study Start Date : January 6, 2015
Actual Primary Completion Date : April 15, 2015
Actual Study Completion Date : April 15, 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

Arm Intervention/treatment
Experimental: Cohort 1
Participants received PF-04958242 oral capsule, 0.20 mg, twice a day for 14 days
Drug: PF-04958242
Administered as specified in the treatment arm

Experimental: Cohort 2
Participants received PF-04958242 oral capsule, 0.35 mg, twice a day for 14 days
Drug: PF-04958242
Administered as specified in the treatment arm

Placebo Comparator: Matching Placebo
Participants received matching placebo oral capsule, twice a day dosing for 14 days
Drug: Placebo
Administered as specified in the treatment arm




Primary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) (Single Dose) [ Time Frame: Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, and 12 hours post-dose) ]
  2. Cmax (Steady State) [ Time Frame: 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 ]
    Cmax steady state for PF-04958242 0.25 mg group and PF-04958242 0.475 mg group at Day 14 were presented.

  3. Time for Cmax (Tmax) (Single Dose) [ Time Frame: Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, and 12 hours post-dose) ]
  4. Tmax (Steady State) [ Time Frame: 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 ]
    Tmax steady state for PF-04958242 0.25 mg group and PF-04958242 0.475 mg group at Day 14 were presented.

  5. Area Under the Concentration-Time Profile From Time 0 to Time Tau (τ), the Dosing Interval, Where τ = 12 Hours (AUCτ) (Single Dose) [ Time Frame: Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, and 12 hours post-dose) ]
  6. AUCτ (Steady State) [ Time Frame: 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 ]
    AUCτ steady state for PF-04958242 0.25 mg group and PF-04958242 0.475 mg group at Day 14 were presented.

  7. Apparent Oral Clearance (CL/F) (Steady State) [ Time Frame: 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 ]
    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.

  8. Apparent Volume of Distribution (Vz/F) (Steady State) [ Time Frame: 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 ]
    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.

  9. Terminal Half-Life (t1/2) (Steady State) [ Time Frame: 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 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.

  10. Observed Accumulation Ratio (Rac) (Steady State) [ Time Frame: 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 ]
    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.

  11. Observed Accumulation Ratio for Cmax (Rac, Cmax) (Steady State) [ Time Frame: 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 ]
    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.

  12. Peak-to-Trough Ratio at Steady State (PTR) [ Time Frame: 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 ]
    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.

  13. Number of Participants With Abnormal Clinical Laboratory Measurements [ Time Frame: Baseline up to Day 21 ]
    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).

  14. Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern [ Time Frame: Baseline up to Day 21 ]
    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.

  15. Number of Participants With Electrocardiogram Data Meeting Criteria of Potential Clinical Concern [ Time Frame: Baseline up to Day 21 ]
    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.

  16. Number of Participants With Abnormalities in Neurological Examination [ Time Frame: Baseline up to Day 21 ]
    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).

  17. Number of Participants With Abnormalities in Physical Examination [ Time Frame: Baseline up to Day 21 ]
    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.

  18. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 28 days after last study drug administration ]
    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.

  19. Number of Participants With Positive Response to Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline up to Day 21 ]
    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").



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Psychiatrically stable (≥3 months) male and female subjects with schizophrenia of non-childbearing potential between the ages of 18 and 55 years, inclusive.
  • Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >55 kg (121 lbs).
  • DSM-IV Diagnosis of Schizophrenia; on stable medication treatment regimen ≥2 months.

Key Exclusion Criteria:

  • Suicide attempt within 3 months prior to screening.
  • History of or risk of seizures; head injury with long term abnormal resulting condition, abnormal EEG, clinically significant additional diseases or conditions, current medication with a significant risk of seizures, currently receiving antipsychotic medications.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02332798


Locations
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United States, California
Collaborative Neuroscience Network, LLC.
Long Beach, California, United States, 90806
Sponsors and Collaborators
Biogen
Investigators
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Study Director: Medical Director Biogen

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Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT02332798    
Other Study ID Numbers: B1701017
MAD ( Other Identifier: Alias Study Number )
First Posted: January 7, 2015    Key Record Dates
Results First Posted: June 14, 2016
Last Update Posted: January 9, 2020
Last Verified: December 2019
Keywords provided by Biogen:
Multiple ascending doses
safety
tolerability
pharmacokinetics
cognitive impairment associated with schizophrenia (CIAS)
Additional relevant MeSH terms:
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Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders