Clinical trial NCT02341482: A Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of PF-04958242 in Healthy Subjects
Official title: A Phase 1, Open-label, Fixed-sequence Study To Estimate The Effects Of Multiple-dose Administration Of Itraconazole On The Pharmacokinetics Of Pf 04958242 In Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Itraconazole
Healthy Volunteers
Drug-drug interaction
PF-04958242
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2015-01-19
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the current study is to characterize the pharmacokinetic (PK) profile of PF 04958242 when co administered with a strong cytochrome P450 3A4 (CYP3A4) inhibitor.

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

Eligibility criteria: Key Inclusion Criteria:

-Healthy male subjects and female subjects of non childbearing with a Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>55 kg (121 lbs).

Key Exclusion Criteria:

* Subjects with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat, if deemed necessary:

  * Aspartate transaminase (AST)/serum glutamic oxaloacetic transminase (SGOT) or alanine transaminase (ALT)/serum glutamic pyruvic transminase (SGPT) \>=1 x upper limit of normal (ULN);
  * Total bilirubin \>=1.5 x ULN; subjects with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is \<= ULN.
* Subjects with epilepsy, or history of epilepsy, or conditions that lower seizure threshold, seizures of any etiology (including substance or drug withdrawal), or who have increased risk of seizures as evidenced by self reported history of electroencephalogram (EEG) with epileptiform activity. Subjects with a history of childhood seizures and history of head trauma with loss of consciousness requiring hospitalization overnight will be excluded as well.
* Subjects who had a history of allergy or intolerance to azole antifungal drugs.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Primary outcomes:
measure: Area Under the Concentration-Time Profile From Time 0 to Time Tau, the Dosing Interval, Where Tau = 12 Hours (AUCtau) of PF-04958242
timeFrame: Day 1 (0,1.5,12,13.5 hours post-dose), Day 2 (0,1.5,12,13.5 hours post-dose), Day 3 (0,0.5,1,1.5,2,3,4,6,8,12 hours post-dose), Day 4, Day 7, Day 10, Day 13, Day 16, Day 17 (0,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose) Day 18, Day 19, Day 20, Day 21
measure: Maximum Observed Plasma Concentration (Cmax) of PF-04958242
timeFrame: Day 1 (0,1.5,12,13.5 hours post-dose), Day 2 (0,1.5,12,13.5 hours post-dose), Day 3 (0,0.5,1,1.5,2,3,4,6,8,12 hours post-dose), Day 4, Day 7, Day 10, Day 13, Day 16, Day 17 (0,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose) Day 18, Day 19, Day 20, Day 21
Secondary outcomes:
measure: Time for Cmax (Tmax) of PF-04958242
timeFrame: Day 1 (0,1.5,12,13.5 hours post-dose), Day 2 (0,1.5,12,13.5 hours post-dose), Day 3 (0,0.5,1,1.5,2,3,4,6,8,12 hours post-dose), Day 4, Day 7, Day 10, Day 13, Day 16, Day 17 (0,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose) Day 18, Day 19, Day 20, Day 21
measure: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-04958242
timeFrame: Day 1 (0,1.5,12,13.5 hours post-dose), Day 2 (0,1.5,12,13.5 hours post-dose), Day 3 (0,0.5,1,1.5,2,3,4,6,8,12 hours post-dose), Day 4, Day 7, Day 10, Day 13, Day 16, Day 17 (0,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose) Day 18, Day 19, Day 20, Day 21
measure: Predose Concentration (Ctrough) of PF-04958242
timeFrame: 0 hour at Day 1, Day 2, Day 3, Day 4, Day 7, Day 10, Day 13, Day 16, and Day 17 (pre-dose)
measure: Apparent Oral Clearance (CL/F) of PF-04958242
timeFrame: Day 1 (0,1.5,12,13.5 hours post-dose), Day 2 (0,1.5,12,13.5 hours post-dose), Day 3 (0,0.5,1,1.5,2,3,4,6,8,12 hours post-dose), Day 4, Day 7, Day 10, Day 13, Day 16, Day 17 (0,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose) Day 18, Day 19, Day 20, 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 Significant Change in Neurological Examination From Previous Examination
timeFrame: Baseline up to Day 21
measure: Number of Participants With Significant Change in Physical Examination From Previous 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
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Pfizer New Haven Clinical Research Unit
state: Connecticut
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: