Effect of Multiple Doses of Itraconazole on the Pharmacokinetics of a Single-Dose of PF-06651600 in Healthy Participants

A PHASE 1, OPEN-LABEL, FIXED SEQUENCE 2-PERIOD STUDY TO INVESTIGATE THE EFFECT OF MULTIPLE DOSES OF ITRACONAZOLE ON THE PHARMACOKINETICS OF A SINGLE DOSE OF PF-06651600 IN HEALTHY PARTICIPANTS

This study will estimate the impact of a strong CYP3A4 inhibitor (itraconazole) on the pharmacokinetics of an investigational product (PF-06651600) in healthy adult participants.

This is an open-label, fixed sequence two period study with healthy participants that will receive a single dose of PF-06651600 alone and co-administered with multiple doses of itraconazole at a single center.

Participants will be screened within 28 days of the first dose of the investigational products and if entry criteria are met, the participant will report to the clinic on the day before the Day 1 visit. On Day 1 of Period 1, each participant will receive a 30 mg dose of PF-06651600 and PK samples will be collected for 48 hours. In Period 2, participants will receive itraconazole solution from Day 1-5. On Day 4 of Period 2 the participant will receive 30 mg of PF-06651600 with the itraconazole. PK samples will be collected up to 48 hours after the PF-06651600 dose. Participants will be confined for a total of 9 days in the clinic. The participant will be followed up by phone contact.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: PF-06651600 10 mg tablets; Drug: Itraconazole Solution 200 mg

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Be-bru
    • Brussels, Be-bru, Belgium, B-1070
      • Pfizer Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations and other study procedures.
• Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg.

Exclusion Criteria:

• Evidence of congestive heart failure or history of congestive heart failure or any of the following: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident including transient ischemic attack or pulmonary embolus.
• Known hypersensitivity to itraconazole or it excipients or to other azole antifungals.
• Infection with Hepatitis B, C or HIV
• Known present or history of malignancy other than a successfully treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: PF-06651600 treatment arm; This arm includes two treatment periods. Period 1-Single oral dose of PF-06651600 30 mg as tablets on Day 1 followed by Period 2 in which itraconazole 200 mg (oral solution) is given for 5 days. On Day 4 of Period 2, a single oral dose of PF-06651600 30 mg is given with itraconazole

Drug: PF-06651600 10 mg tablets; On Day 1 in Period 1, a single oral dose of 30 mg (3 x 10 mg tablets) will be administered. On Day 4 of Period 2, a single oral dose of 30 mg (3 x 10 mg tablets) will be administered after itraconazole.; Drug: Itraconazole Solution 200 mg; Itraconazole 200 mg will be administered as 20 mL (10 mg/mL) oral solution once daily on Days 1-5 in Period 2. On Day 4 of Period 2, co-administration of itraconazole 200 mg and PF-06651600 30 mg will occur. Itraconazole will be administered first followed by PF-06651600 tablets.; Other Names: Sporanox Oral Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single dose Area under the curve from time zero to infinity [AUC (0-inf)] of PF-06651600	Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinity.	0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24 and 48 hours
Maximum observed plasma concentration of PF-06651600	Peak concentration of PF-06651600	0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24 and 48 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of treatment-emergent adverse events (AEs)	Baseline up to 35 days
Number of adverse events leading to discontinuation	Baseline up to 35 days
Number of participants with clinically significant change in vital signs from Baseline	Baseline to Day 9
Number of participants with clinically significant abnormalities in clinical laboratory values	Baseline to Day 9

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2019
• Primary Completion (Actual): April 6, 2019
• Study Completion (Actual): June 4, 2019

Study Registration Dates

• First Submitted: January 28, 2019
• First Submitted That Met QC Criteria: January 28, 2019
• First Posted (Actual): January 29, 2019

Study Record Updates

• Last Update Posted (Actual): June 28, 2019
• Last Update Submitted That Met QC Criteria: June 27, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Itraconazole; CYP3A4; PF-06651600; Drug-Drug Interaction
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Pharmaceutical Solutions; Itraconazole
• Other Study ID Numbers: B7981023; 2018-004664-55 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No