Study To Evaluate The Safety, Tolerability And Pharmacokinetics Of Single Doses Of PF-04958242 In Healthy Volunteers

• ClinicalTrials.gov Identifier: NCT02228395
• Recruitment Status: Completed
• First Posted: August 29, 2014
• Results First Posted: December 17, 2015
• Last Update Posted: January 7, 2020
• Sponsor: Biogen
• Information provided by (Responsible Party): Biogen

Study Description

Brief Summary:

This study aims to assess the safety, tolerability, and pharmacokinetics of PF-04958242 at a number of single ascending doses in healthy volunteers

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

Detailed Description:

This study was previously posted by Pfizer, Inc. Sponsorship of the trial was transferred to Biogen.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: A Phase 1, Randomized, Subject- And Investigator-blind, Sponsor Open, Placebo Controlled, Single Ascending Dose Escalation Study To Evaluate The Safety, Tolerability And Pharmacokinetics Of Pf-04958242 Following Oral Dose Capsules in Healthy Subjects
• Actual Study Start Date: September 22, 2014
• Actual Primary Completion Date: November 13, 2014
• Actual Study Completion Date: November 13, 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1; Participants received 1 single dose of placebo, PF-04958242 0.6 mg, and PF-04958242 0.8 mg orally during 3 periods, respectively. There was at least a 10-day washout period between each dosing.	Drug: PF-04958242; Administered as specified in treatment arm; Drug: Placebo; Administered as specified in treatment arm
Experimental: Cohort 2; Participants received 1 single dose of PF-04958242 0.35 mg, placebo, and PF-04958242 0.8 mg orally during 3 periods, respectively. There was at least a 10-day washout period between each dosing.	Drug: PF-04958242; Administered as specified in treatment arm; Drug: Placebo; Administered as specified in treatment arm
Experimental: Cohort 3; Participants received 1 single dose of PF-04958242 0.35 mg, PF-04958242 0.6 mg, and placebo orally during 3 periods, respectively. There was at least a 10-day washout period between each dosing.	Drug: PF-04958242; Administered as specified in treatment arm; Drug: Placebo; Administered as specified in treatment arm

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Post-Baseline [ Time Frame: Baseline up to Day 10 ]
   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").
2. Number of Participants With Treatment-Emergent 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. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. 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.
3. Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern [ Time Frame: Baseline up to Day 10 ]
   The following laboratory parameters were analyzed: 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, uric acid, albumin, and total protein; urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin and microscopy [if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase]); others (follicle stimulating hormone [FSH], and urine drug screening).
4. Number of Participants With Potentially Clinically Significant Vital Signs Findings [ Time Frame: Baseline up to Day 10 ]
   Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine/sitting pulse rate <40 or >120 beats per minute (bpm), standing pulse rate <40 or >140 bpm; systolic blood pressure (SBP) >=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.
5. Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings [ Time Frame: Baseline up to Day 10 ]
   ECG parameters included pulse rate (PR) interval, QRS interval, corrected QT interval using Bazett's formula (QTcB)and corrected QT interval using Fridericia's formula (QTcF). Criteria for ECG changes meeting potential clinical concern included: PR interval greater than or equal to (>=)300 milliseconds (msec) or >=25% increase when baseline is greater than (>)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 QTcF >=450 msec or >=30 msec increase. The number of participants with potentially clinically significant ECG findings at any visit were reported.
6. Number of Participants With Abnormal Physical Examination Findings [ Time Frame: Baseline up to Day 10 ]
   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.
7. Number of Participants With Abnormal Neurological Examination Findings [ Time Frame: Baseline up to Day 10 ]
   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)

Secondary Outcome Measures :

1. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12, 24, 36, 48, 72, 96, 120, 168 and 216 hours post-dose ]
2. Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12, 24, 36, 48, 72, 96, 120, 168 and 216 hours post-dose ]
3. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12, 24, 36, 48, 72, 96, 120, 168 and 216 hours post-dose ]
4. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) [ Time Frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12, 24, 36, 48, 72, 96, 120, 168 and 216 hours post-dose ]
5. Apparent Clearance (CL/F) [ Time Frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12, 24, 36, 48, 72, 96, 120, 168 and 216 hours post-dose ]
6. Apparent Volume of Distribution (Vz/F) [ Time Frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12, 24, 36, 48, 72, 96, 120, 168 and 216 hours post-dose ]
7. Terminal Elimination Half-Life (t1/2) [ Time Frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12, 24, 36, 48, 72, 96, 120, 168 and 216 hours post-dose ]
   Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half.
8. Dose Normalized Cmax (Cmax[dn]) [ Time Frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12, 24, 36, 48, 72, 96, 120, 168 and 216 hours post-dose ]
9. Dose Normalized AUClast (AUClast[dn]) [ Time Frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12, 24, 36, 48, 72, 96, 120, 168 and 216 hours post-dose ]
10. Dose Normalized AUCinf (AUCinf[dn]) [ Time Frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12, 24, 36, 48, 72, 96, 120, 168 and 216 hours post-dose ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Key Inclusion Criteria:

• Healthy female subjects of non-childbearing potential and/or male subjects between the ages of 18 and 55 years, inclusive (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests).
• Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >55 kg

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).
• Other 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 subject inappropriate for entry into this study.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Contacts and Locations

Locations

United States, Connecticut

New Haven Clinical Research Unit

New Haven, Connecticut, United States, 06511

Sponsors and Collaborators

Biogen

Investigators

• Study Director: Medical Director; Biogen

More Information

• Responsible Party: Biogen
• ClinicalTrials.gov Identifier: NCT02228395
• Other Study ID Numbers: B1701016; SAD-MAD ( Other Identifier: Alias Study Number )
• First Posted: August 29, 2014
• Results First Posted: December 17, 2015
• Last Update Posted: January 7, 2020
• Last Verified: December 2019

Keywords provided by Biogen:

Single ascending doses; pharmacokinetics; safety; tolerability; healthy volunteers; cognitive impairment associated with schizophrenia (CIAS)