Healthy
Conditions
Keywords
Palbociclib, PD-0332991, Proton Pump Inhibitor, DDI, Healthy Volunteers, Pharmacokinetics, Rabeprazole
Brief summary
Fixed sequence, 2-period crossover study to compare the pharmacokinetic profiles of Palbociclib in absence and presence of prior administration of proton pump inhibitor Rabeprazole. The increased gastric pH achieved by the treatment with multiple doses of Rabeprazole might affect the absorption process of Palbociclib.
Interventions
Single dose of 125mg Palbociclib capsule will be administered to subjects orally and then PK samples will be collected at 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours.
Two Rabeprazole 20mg tablets will be given to subjects orally once daily for 7 days. Then on the same day at least 4 hours after the last dose of Rabeprazole, single dose of 125mg Palbociclib capsule will be given to subjects orally then followed by PK samplings at 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours.
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
* Female subjects of non-childbearing potential; Healthy subjects identified by a detailed medical history, full physical examination including blood pressure and pulse rate measurement, 12-lead ECG or clinical laboratory test.
Exclusion criteria
* A positive urine drug screen, urine cotinine test or alcohol breath test. * Treatment with an investigational drug within 30 days or 5 half-lives preceding the first dose of study medication. * Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives prior to the first dose of study medication. All antacid agents must be discontinued 28 days prior to the first dose of study medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] | 0-120 hours | AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8). |
| Maximum Observed Plasma Concentration (Cmax) | 0-120 hours | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Oral Clearance (CL/F) | 0-120 hours | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0-120 hours | — |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] | 0-120 hours | AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t) |
| Apparent Volume of Distribution (Vz/F) | 0-120 hours | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. |
| Plasma Decay Half-Life (t1/2) | 0-120 hours | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Time For the Last Quantifiable Concentration (Tlast) | 0-120 hours | — |
| Area Under the Curve from Time Zero to 72 hours | 0-72 hours | AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to 72 hours |
Countries
United States
Outcome results
None listed