A Pilot Study To Investigate The Effect Of Concurrent Antacid Administration On The Bioavailability Of Six Experimental Formulations Of Palbociclib
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1 Cohort 1 will receive a 125 mg round yellow palbociclib tablet containing succinic acid |
Drug: Palbociclib Alone
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.
Other Names:
Drug: Palbociclib + Rabeprazole
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.
Other Names:
|
| Experimental: Cohort 2 Cohort 2 will receive a 125 mg oval yellow palbociclib spray-dried dispersion tablet containing HMPC E3 |
Drug: Palbociclib Alone
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.
Other Names:
Drug: Palbociclib + Rabeprazole
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.
Other Names:
|
| Experimental: Cohort 3 Cohort 3 will receive a 125 mg oval yellow palbociclib spray-dried dispersion tablet with HMPC E3 and succinic acid. |
Drug: Palbociclib Alone
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.
Other Names:
Drug: Palbociclib + Rabeprazole
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.
Other Names:
|
| Experimental: Cohort 4 Cohort 4 will receive a 125 mg oval white/yellow palbociclib bilayer tablet with tartaric and succinic acid. |
Drug: Palbociclib Alone
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.
Other Names:
Drug: Palbociclib + Rabeprazole
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.
Other Names:
|
| Experimental: Cohort 5 Cohort 5 will receive a 125 mg oval yellow palbociclib fluid bed granulation tablet with succinic acid. |
Drug: Palbociclib Alone
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.
Other Names:
Drug: Palbociclib + Rabeprazole
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.
Other Names:
|
| Experimental: Cohort 6 Cohort 6 will receive a 125 mg palbociclib oral solution |
Drug: Palbociclib Alone
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.
Other Names:
Drug: Palbociclib + Rabeprazole
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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- AUCinf [Pre-dose to 120 hours post-dose]
Area under the concentration-time curve from time zero to infinity.
- Cmax [Pre-dose to 120 hours post-dose]
Maximum observed plasma concentration
Secondary Outcome Measures
- AUClast [Pre-dose to 120 hours post-dose]
Area under the concentration-time curve from time zero to the time of the last quantifiable concentration.
- CL/F [Pre-dose to 120 hours post-dose]
Apparent oral clearance from plasma
- Tmax [Pre-dose to 120 hours post-dose]
Time of the maximum observed concentration post-dose.
- Vz/F [Pre-dose to 120 hours post-dose]
Apparent volume of distribution
- t1/2 [Pre-dose to 120 hours post-dose]
Terminal phase half-life
Eligibility Criteria
Criteria
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:
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Any condition possibly affecting drug absorption (eg, gastrectomy)
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A positive urine drug or cotinine test
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A known history of hypersensitivity to palbociclib
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A supine systolic blood pressure >140 mmHg, or a QTc >450 msec.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | MRA Clinical Research - Phase 1 | Miami | Florida | United States | 33143 |
| 2 | Miami Research Associates, LLC | South Miami | Florida | United States | 33143 |
| 3 | MRA Clinical Research, LLC | South Miami | Florida | United States | 33143 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- A5481041