Study to Evaluate the Safety, Tolerability and Pharmacokinetics of PF-04958242 in Healthy Adult Volunteers

Study Overview
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Brief Summary
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The primary objective of this study evaluates the safety and tolerability of multiple, escalating doses of PF-04958242 administered orally to healthy adult participants.This study also evaluates the plasma and urine multiple dose pharmacokinetics (PK) of PF-04958242.

Detailed Description
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A decision was made to terminate the B1701002 study so that emerging data from the study and from a preclinical study in rats could be further examined and incorporated into a new study design and protocol. This study was previously posted by Pfizer, Inc. Sponsorship of the trial was transferred to Biogen.

Official Title
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A Phase I, Randomized, Subject and Investigator-Blind, Sponsor Open, Multiple Escalating Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of PF-04958242 in Healthy Adult Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: PF-04958242
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Body Mass Index (BMI) of 17.5 to 30.5 kilograms per meter quared (kg/m2); Total body weight >50 kilograms (kg) (110 pounds [lbs]); Key Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing); Positive urine drug screen; Pregnant or nursing females, and females of child bearing potential; Severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Participants received an oral solution of 0.03 milligrams (mg) of PF-04958242, every 12 hours for 14 days. | Drug: PF-04958242<br>* Administered as specified in the treatment arm<br>|
| Experimental: Cohort 2<br>Participants received an oral solution of 0.05 mg of PF-04958242, every 24 hours for 14 days. | Drug: PF-04958242<br>* Administered as specified in the treatment arm<br>|
| Experimental: Cohort 3<br>Participants received an oral solution of 0.10 mg of PF-04958242, every 24 hours for 14 days. | Drug: PF-04958242<br>* Administered as specified in the treatment arm<br>|
| Experimental: Cohort 4<br>Participants received an oral solution of 0.15 mg of PF-04958242, every 24 hours for 14 days. | Drug: PF-04958242<br>* Administered as specified in the treatment arm<br>|
| Experimental: Cohort 5<br>Participants received an oral solution of 0.20 mg of PF-04958242, every 24 hours for 14 days. | Drug: PF-04958242<br>* Administered as specified in the treatment arm<br>|
| Experimental: Cohort 6<br>Participants received an oral solution of 0.25 mg of PF-04958242, every 24 hours for 14 days. | Drug: PF-04958242<br>* Administered as specified in the treatment arm<br>|
| Placebo Comparator: Matching Placebo<br>Participants received an oral solution of matching placebo, every 12 or 24 hours for 14 days. | Drug: Placebo<br>* Administered as specified in the treatment arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Adverse Events and Serious Adverse Events | An adverse event is any untoward medical occurrence in a clinical investigation subject administered a product or medical device. A serious adverse event or serious adverse drug reaction is any untoward medical occurrence at any dose that: Results in death; Is life-threatening (immediate risk of death); Requires inpatient hospitalization or prolongation of existing hospitalization; Results in persistent or significant disability/incapacity; Results in congenital anomaly/birth defect. | Baseline up to Day 23 | 
| Maximum Plasma Drug Concentration (Cmax) for Single Dose |  | Day 1 and at multiple time points up to Day 17 | 
| Time to Reach Maximum Plasma Concentration (Tmax) for Single Dose |  | Day 1 and at multiple time points up to Day 17 | 
| Area Under the Concentration Time-curve During a Dosage Interval (AUCτ) for Single Dose |  | Day 1 and at multiple time points up to Day 17 | 
| Maximum Observed Plasma Concentration (Cmax) for Steady State |  | Day 1 and at multiple time points up to Day 17 | 
| Area Under the Plasma Drug Concentration-Time Curve During a Dosage Interval (AUCτ) for Steady State |  | Day 1 and at multiple time points up to Day 17 | 
| Apparent Total Clearance of the Drug from Plasma (CL/F) for Steady State |  | Day 1 and at multiple time points up to Day 17 | 
| Apparent Volume of Distribution During Terminal Phase (Vz/F) for Steady State |  | Day 1 and at multiple time points up to Day 17 | 
| Elimination Half-Life (t1/2) for Steady State |  | Day 1 and at multiple time points up to Day 17 | 
| Accumulation Ratio (AUC(τ,ss)/AUC(τ,sd)) for Steady State |  | Day 1 and at multiple time points up to Day 17 | 
| Percent of Dose Eliminated in Urine Unchanged (Ae%) |  | Day 14 | 
| Amount of PF-04958242 Eliminated in Urine Unchanged (Ae) |  | Day 14 | 
| Renal Clearance (CLr) |  | Day 14 | 
| Time to Reach Maximum Plasma Concentration (Tmax) for Steady State |  | Day 1 and at multiple time points up to Day 17 |