A Pilot Study To Investigate The Effect Of Concurrent Antacid Administration On The Bioavailability Of Six Experimental Formulations Of Palbociclib

Study Overview
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Brief Summary
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This study will investigate whether concurrent administration of rabeprazole, an antacid known as a proton pump inhibitor, alters the absorption of the drug palbociclib when given as one of six experimental formulations.

Detailed Description
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This will be a 6 cohort study investigating one experimental formulation of palbociclib in each of the six cohorts of 10 healthy subjects. Each cohort will receive two treatments in a fixed-sequence. In Period 1, all subjects will receive a single 125mg dose of palbociclib alone and undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose. In Period 2, all subjects will receive daily 40mg doses of Rabeprazole for 7 consecutive days, and approximately 4 hours after the Day 7 rabeprazole dose each subject will receive a single 125mg dose of palbociclib. Subjects will undergo serial pharmacokinetic blood sampling up to 120 hours post-dose.

Official Title
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A Phase 1, Open-Label Fixed-Sequence 2-Period Crossover Study Of Palbociclib (pd-0332991) In Healthy Volunteers To Estimate The Effect Of Antacid Treatment On The Bioavailability Of A 125 Mg Single Dose Of Six Experimental Formulations Of Palbociclib Relative To Palbociclib Administration Alone Under Fasted Conditions

Conditions
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Healthy

Intervention / Treatment
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* Drug: Palbociclib Alone
* Drug: Palbociclib + Rabeprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Male or Female of non-childbearing potential, Having a body weight >50 kg Having a bopy mass index (BMI) between 17.5 and 30.5 kg/m2. Exclusion Criteria: Any condition possibly affecting drug absorption (eg, gastrectomy) A positive urine drug or cotinine test A known history of hypersensitivity to palbociclib A supine systolic blood pressure >140 mmHg, or a QTc >450 msec.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Cohort 1 will receive a 125 mg round yellow palbociclib tablet containing succinic acid | Drug: Palbociclib Alone<br>* In Period 1 of each Cohort, a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.<br>* Other names: Palbociclib, PD-0332991;Drug: Palbociclib + Rabeprazole<br>* In Period 2 of each Cohort, subjects will receive daily 40 mg oral doses of the proton pump inhibitor rabeprazole on 7 consecutive days. Approximately 4 hours after the last rabeprazole dose a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.<br>* Other names: Palbociclib, PD-0332991, Rabeprazole, Aciphex, Proton Pump Inhibitor, PPI;|
| Experimental: Cohort 2<br>Cohort 2 will receive a 125 mg oval yellow palbociclib spray-dried dispersion tablet containing HMPC E3 | Drug: Palbociclib Alone<br>* In Period 1 of each Cohort, a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.<br>* Other names: Palbociclib, PD-0332991;Drug: Palbociclib + Rabeprazole<br>* In Period 2 of each Cohort, subjects will receive daily 40 mg oral doses of the proton pump inhibitor rabeprazole on 7 consecutive days. Approximately 4 hours after the last rabeprazole dose a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.<br>* Other names: Palbociclib, PD-0332991, Rabeprazole, Aciphex, Proton Pump Inhibitor, PPI;|
| Experimental: Cohort 3<br>Cohort 3 will receive a 125 mg oval yellow palbociclib spray-dried dispersion tablet with HMPC E3 and succinic acid. | Drug: Palbociclib Alone<br>* In Period 1 of each Cohort, a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.<br>* Other names: Palbociclib, PD-0332991;Drug: Palbociclib + Rabeprazole<br>* In Period 2 of each Cohort, subjects will receive daily 40 mg oral doses of the proton pump inhibitor rabeprazole on 7 consecutive days. Approximately 4 hours after the last rabeprazole dose a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.<br>* Other names: Palbociclib, PD-0332991, Rabeprazole, Aciphex, Proton Pump Inhibitor, PPI;|
| Experimental: Cohort 4<br>Cohort 4 will receive a 125 mg oval white/yellow palbociclib bilayer tablet with tartaric and succinic acid. | Drug: Palbociclib Alone<br>* In Period 1 of each Cohort, a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.<br>* Other names: Palbociclib, PD-0332991;Drug: Palbociclib + Rabeprazole<br>* In Period 2 of each Cohort, subjects will receive daily 40 mg oral doses of the proton pump inhibitor rabeprazole on 7 consecutive days. Approximately 4 hours after the last rabeprazole dose a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.<br>* Other names: Palbociclib, PD-0332991, Rabeprazole, Aciphex, Proton Pump Inhibitor, PPI;|
| Experimental: Cohort 5<br>Cohort 5 will receive a 125 mg oval yellow palbociclib fluid bed granulation tablet with succinic acid. | Drug: Palbociclib Alone<br>* In Period 1 of each Cohort, a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.<br>* Other names: Palbociclib, PD-0332991;Drug: Palbociclib + Rabeprazole<br>* In Period 2 of each Cohort, subjects will receive daily 40 mg oral doses of the proton pump inhibitor rabeprazole on 7 consecutive days. Approximately 4 hours after the last rabeprazole dose a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.<br>* Other names: Palbociclib, PD-0332991, Rabeprazole, Aciphex, Proton Pump Inhibitor, PPI;|
| Experimental: Cohort 6<br>Cohort 6 will receive a 125 mg palbociclib oral solution | Drug: Palbociclib Alone<br>* In Period 1 of each Cohort, a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.<br>* Other names: Palbociclib, PD-0332991;Drug: Palbociclib + Rabeprazole<br>* In Period 2 of each Cohort, subjects will receive daily 40 mg oral doses of the proton pump inhibitor rabeprazole on 7 consecutive days. Approximately 4 hours after the last rabeprazole dose a single 125 mg dose of palbociclib will be administered alone in a fasted state, and subjects will undergo serial pharmacokinetic blood sampling for up to 120 hours post-dose.<br>* Other names: Palbociclib, PD-0332991, Rabeprazole, Aciphex, Proton Pump Inhibitor, PPI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCinf | Area under the concentration-time curve from time zero to infinity. | Pre-dose to 120 hours post-dose | 
| Cmax | Maximum observed plasma concentration | Pre-dose to 120 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUClast | Area under the concentration-time curve from time zero to the time of the last quantifiable concentration. | Pre-dose to 120 hours post-dose | 
| CL/F | Apparent oral clearance from plasma | Pre-dose to 120 hours post-dose | 
| Tmax | Time of the maximum observed concentration post-dose. | Pre-dose to 120 hours post-dose | 
| Vz/F | Apparent volume of distribution | Pre-dose to 120 hours post-dose | 
| t1/2 | Terminal phase half-life | Pre-dose to 120 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Palbociclib, Rabeprazole, Proton Pump Inhibitor, Drug Interaction Study, DDI