Clinical trial NCT02332798: Multiple Ascending Doses of PF-04958242 in Subjects With Stable Schizophrenia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Schizophrenia
Keywords: Multiple ascending doses
safety
tolerability
pharmacokinetics
cognitive impairment associated with schizophrenia (CIAS)
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2015-01-07
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility 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

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) (Single Dose)
timeFrame: Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, and 12 hours post-dose)
measure: Cmax (Steady State)
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
measure: Time for Cmax (Tmax) (Single Dose)
timeFrame: Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, and 12 hours post-dose)
measure: Tmax (Steady State)
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
measure: Area Under the Concentration-Time Profile From Time 0 to Time Tau (τ), the Dosing Interval, Where τ = 12 Hours (AUCτ) (Single Dose)
timeFrame: Day 1 (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, and 12 hours post-dose)
measure: AUCτ (Steady State)
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
measure: Apparent Oral Clearance (CL/F) (Steady State)
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
measure: Apparent Volume of Distribution (Vz/F) (Steady State)
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
measure: Terminal Half-Life (t1/2) (Steady State)
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
measure: Observed Accumulation Ratio (Rac) (Steady State)
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
measure: Observed Accumulation Ratio for Cmax (Rac, Cmax) (Steady State)
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
measure: Peak-to-Trough Ratio at Steady State (PTR)
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
measure: Number of Participants With Abnormal Clinical Laboratory Measurements
timeFrame: Baseline up to Day 21
measure: Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern
timeFrame: Baseline up to Day 21
measure: Number of Participants With Electrocardiogram Data Meeting Criteria of Potential Clinical Concern
timeFrame: Baseline up to Day 21
measure: Number of Participants With Abnormalities in Neurological Examination
timeFrame: Baseline up to Day 21
measure: Number of Participants With Abnormalities in Physical Examination
timeFrame: Baseline up to Day 21
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 28 days after last study drug administration
measure: Number of Participants With Positive Response to Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline up to Day 21
Secondary outcomes:
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Collaborative Neuroscience Network, LLC.
state: California
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: