PPI And Food Effect Study For PF-06463922 In Healthy Volunteers

A Phase 1, Randomized, Crossover, Open-Label, 4 Period Study In Healthy Volunteers To Demonstrate The Lack Of Effect Of Rabeprazole And Food On The Pharmacokinetics Of PF-06463922 And To Assess The Relative Bioavailability Of Oral Solution To The Tablet Formulation Of PF-06463922

The current study will be conducted in healthy adult subjects to evaluate the effect of proton pump inhibitor and food on pharmacokinetics of PF-06463922, to evaluate the bioavailability of the oral solution relative to the tablet formulation of PF-06463922.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PF-06463922; Drug: rabeprazole

Detailed Description

PF-06463922 is a selective, ATP competitive small molecule tyrosine kinase inhibitor (TKI) of the Anaplastic Lymphoma Kinase (ALK) positive (ALK+) or ROS oncogene 1 (ROS1) positive (ROS1+) receptor tyrosine kinases (RTK) that also potently inhibits ALK kinase domain mutations responsible for resistance to crizotinib. PF-06463922 is being developed as a novel anticancer agent for the treatment of patients with advanced ALK+ NSCLC or ROS1+ NSCLC.

The current study is a Phase 1, randomized, open label, 4 period, 4 treatment, 4 sequence, crossover study conducted in healthy adult subjects. Each subject will receive four single oral doses of 100 mg PF-06463922 as tablets alone, tablets with food, tablets with rabeprazole, and oral solution after overnight fasting with at least a 10 day washout period between each PF-06463922 dose.

Twenty four (24) subjects will be enrolled to obtain at least 20 evaluable subjects who complete all treatments. Subjects who withdraw will not be replaced unless the total number of completed subjects falls below 20.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Healthy female subjects of non-childbearing potential and/or male subjects
• Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
• Evidence of a personally signed and dated informed consent document.
• Subject must be willing to avoid direct sunlight exposure or any high intensity ultraviolet light exposure

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular
• Any condition possibly affecting drug absorption
• A positive urine drug screen.
• Use of tobacco- or nicotine containing products within 90 days of screening or a positive urine cotinine test and history of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males within 6 months of Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: PF-06463922; each subject will receive four single doses of PF-06463922 without food, with food, with rabeprazole (without food), and one of the two new formulations without food.

Drug: PF-06463922; each subject will receive 4 single oral doses of 100 mg PF-06463922 (treatment A: tablets without food; treatment B: tablets with food; treatment C: tablets without food with rabeprazole; treatment D: oral solution without food). There will be at least 10 days washout period between consecutive PF-06463922 single dose.; Drug: rabeprazole; 20 mg daily tablets in the evening for 5 days and Pf-06463922 on the morning of day 6 in treatment C.; Other Names: Pariet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
plasma AUCinf for PF-06463922	area under plasma concentration-time profile from time 0 extrapolated to infinite time for PF-06463922	3 months
plasma Cmax for PF-06463922	observed maximal plasma PF-06463922 concentration	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
plasma AUClast for PF-06463922	area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration for PF-06463922	3 months
plasma Tmax for PF-06463922	time to the plasma maximal concentration for PF-06463922	3 months
plasma t1/2 for PF-06463922	plasma terminal half-life for PF-06463922	3 months
plasma CL/F for PF-06463922	apparent clearance for PF-06463922	3 months
plasma Vz/F for PF-06463922	apparent volume of distribution for PF-06463922	3 months

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: December 1, 2015
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: October 5, 2015
• First Submitted That Met QC Criteria: October 5, 2015
• First Posted (Estimate): October 6, 2015

Study Record Updates

• Last Update Posted (Estimate): May 17, 2016
• Last Update Submitted That Met QC Criteria: May 13, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: food effect; rabeprazole; PF-06463922; proton pump inhibitor (PPI); pharmacokinetics(PK)
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Rabeprazole
• Other Study ID Numbers: B7461008; 2015-003416-21 (EudraCT Number); PPI STUDY (Other Identifier: Alias Study Number)