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

• ClinicalTrials.gov Identifier: NCT03821493
• Recruitment Status: Completed
• First Posted: January 29, 2019
• Last Update Posted: June 28, 2019
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Healthy Participants	Drug: PF-06651600 10 mg tablets; Drug: Itraconazole Solution 200 mg	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: 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
• Actual Study Start Date: February 21, 2019
• Actual Primary Completion Date: April 6, 2019
• Actual Study Completion Date: June 4, 2019

Arms and Interventions

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 Name: Sporanox Oral Solution

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Incidence of treatment-emergent adverse events (AEs) [ Time Frame: Baseline up to 35 days ]
2. Number of adverse events leading to discontinuation [ Time Frame: Baseline up to 35 days ]
3. Number of participants with clinically significant change in vital signs from Baseline [ Time Frame: Baseline to Day 9 ]
4. Number of participants with clinically significant abnormalities in clinical laboratory values [ Time Frame: Baseline to Day 9 ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Belgium

Pfizer Clinical Research Unit

Brussels, Be-bru, Belgium, B-1070

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

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

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT03821493
• Other Study ID Numbers: B7981023; 2018-004664-55 ( EudraCT Number )
• First Posted: January 29, 2019
• Last Update Posted: June 28, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• 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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:

PF-06651600; Itraconazole; CYP3A4; Drug-Drug Interaction

Additional relevant MeSH terms:

Itraconazole; Pharmaceutical Solutions; Antifungal Agents; Anti-Infective Agents; 14-alpha Demethylase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Steroid Synthesis Inhibitors; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Cytochrome P-450 CYP3A Inhibitors