A Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of PF-04958242 in Healthy Subjects

NCT02341482 | Completed Phase 1 Results

• 2 other identifiers: B1701021DDI
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Itraconazole; Healthy Volunteers; Drug-drug interaction; PF-04958242

Outcome Measures

Primary Outcomes (2)

• Area Under the Concentration-Time Profile From Time 0 to Time Tau, the Dosing Interval, Where Tau = 12 Hours (AUCtau) of PF-04958242

  AUCtau = area under the concentration-time profile from time 0 to time tau, the dosing interval, where tau = 12 hours. Collected at Day 3 for PF-04958242 0.025 mg Arm and Day 17 for PF-04958242 0.025 mg + itraconazole 200 mg Arm.

  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

• Maximum Observed Plasma Concentration (Cmax) of PF-04958242

  Collected at Day 3 for PF-04958242 0.025 mg Arm and Day 17 for PF-04958242 0.025 mg + itraconazole 200 mg Arm.

  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 (11)

• Time for Cmax (Tmax) of PF-04958242

  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

• Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-04958242

  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

• Predose Concentration (Ctrough) of PF-04958242

  0 hour at Day 1, Day 2, Day 3, Day 4, Day 7, Day 10, Day 13, Day 16, and Day 17 (pre-dose)

• Apparent Oral Clearance (CL/F) of PF-04958242

  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

• Number of Participants With Abnormal Clinical Laboratory Measurements

  Baseline up to Day 21

Study Arms (1)

PF-04958242 and itraconazole

EXPERIMENTAL

PF-04958242 will be provided in a capsule. Participants will receive a 0.10 mg loading dose of PF-04958242 twice daily (BID) on Day 1 then 0.025 mg BID on Day 2-Day 16, with the last dose occurring in the morning on Day 17. Itraconazole will be provided as a solution starting on Day 4. On Day 4, a 200 mg dose of itraconazole will be administered approximately 1 hour before PF-04958242 morning administration and for 13 additional days (Day 4-Day 17).

Drug: PF-04958242; Drug: Itraconazole

Interventions

PF-04958242 DRUG

Administered as specified in the treatment arm

PF-04958242 and itraconazole

Itraconazole DRUG

Administered as specified in the treatment arm

PF-04958242 and itraconazole

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biogen: lead

Study Sites (1)

Pfizer New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

Location

MeSH Terms

Interventions

PF-04958242; Itraconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Results Point of Contact

• Title: Biogen Study Medical Director
• Organization: Biogen

clinicaltrials@biogen.com

866-633-4636

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2015
• First Posted: January 19, 2015
• Study Start: February 5, 2015
• Primary Completion: March 31, 2015
• Study Completion: March 31, 2015
• Last Updated: January 9, 2020
• Results First Posted: June 30, 2016

Record last verified: 2019-12

Locations

US (1)