Healthy
Conditions
Keywords
PF-06463922, rabeprazole, proton pump inhibitor (PPI), pharmacokinetics(PK), food effect
Brief summary
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.
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.
Interventions
DRUGPF-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.
DRUGrabeprazole
20 mg daily tablets in the evening for 5 days and Pf-06463922 on the morning of day 6 in treatment C.
Sponsors
Pfizer
Study design
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| plasma AUCinf for PF-06463922 | 3 months | area under plasma concentration-time profile from time 0 extrapolated to infinite time for PF-06463922 |
| plasma Cmax for PF-06463922 | 3 months | observed maximal plasma PF-06463922 concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| plasma Tmax for PF-06463922 | 3 months | time to the plasma maximal concentration for PF-06463922 |
| plasma Vz/F for PF-06463922 | 3 months | apparent volume of distribution for PF-06463922 |
| plasma CL/F for PF-06463922 | 3 months | apparent clearance for PF-06463922 |
| plasma t1/2 for PF-06463922 | 3 months | plasma terminal half-life for PF-06463922 |
| plasma AUClast for PF-06463922 | 3 months | area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration for PF-06463922 |
Countries
Belgium
Outcome results
None listed