A Drug-Drug Interaction Study To Investigate The Potential For Multiple Doses Of Palbociclib (PD-0332991) To Alter The Pharmacokinetics Of Oral Midazolam In Adult Healthy Women of Non-Childbearing Potential.

Study Overview
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Brief Summary
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This is a drug-drug interaction study to compare the pharmacokinetics of a 2 mg oral dose of midazolam in adult healthy women of non-childbearing potential when administered alone and when administered along with 8 daily 125 mg doses of PD-0332991. Volunteers will be randomized to one of two sequences. Volunteers in sequence 1 will receive midazolam alone in treatment period 1, followed by multiple dose PD-0332991 and midazolam in treatment period 2. Volunteers randomized to sequence 2 will receive multiple dose PD-0332991 and midazolam in treatment period 1, and following a washout period of no less than 14 days they will receive midazolam alone in treatment period 2.

Official Title
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A Phase 1 Randomized, Open-Label, 2-Sequence, 2-Period Crossover Study Of The Effect Of Multiple Doses Of PD-0332991 On Midazolam Pharmacokinetics In Healthy Women of Non-Childbearing Potential

Conditions
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Healthy

Intervention / Treatment
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* Drug: Midazolam
* Drug: PD-0332991
* Drug: Midazolam
* Drug: PD-0332991


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy females of non-child bearing potential between the ages of 18 and 65 years old. A Body Mass Index (BMI) of 17.5 to 32.0 kg/m2 and a total body weight >50 kg (110 lbs). A signed informed consent document. Exclusion Criteria: Any evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease. A positive urine drug screen. Pregnant or nursing females. Treatment with an investigational drug within 30 days or 5 half-lives of the first dose of study medication.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1<br>Subjects randomized to Sequence 1 will receive Treatment A followed by Treatment B. Treatment A is a single 2 mg oral dose of midazolam alone. Treatment B is made up of 8 daily 125 mg oral doses of PD-0332991 and a single 2 mg oral midazolam dose on day 7 immediately after the day 7 PD-0332991 dose. | Drug: Midazolam<br>* Treatment A includes a single 2 mg oral dose of midazolam alone. Treatment B includes a single 2 mg oral midazolam dose on day 7 immediately after the day 7 PD-0332991 dose.<br>Drug: PD-0332991<br>* Treatment B includes 8 daily 125 mg oral doses of PD-0332991.<br>|
| Experimental: Sequence 2<br>Subjects randomized to Sequence 2 will receive Treatment B followed by Treatment A with a washout of no less than 14 days in between.Treatment B is made up of 8 daily 125 mg oral doses of PD-0332991 and a single 2 mg oral midazolam dose on day 7 immediately after the day 7 PD-0332991 dose. There will be a minimum washout of 14 days prior to beginning Treatment A. Treatment A is a single 2 mg oral dose of midazolam alone. | Drug: Midazolam<br>* Treatment B includes a single 2 mg oral midazolam dose on day 7 immediately after the day 7 PD-0332991 dose. Treatment A includes a single 2 mg oral dose of midazolam alone.<br>Drug: PD-0332991<br>* Treatment B is made up of 8 daily 125 mg oral doses of PD-0332991.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Midazolam Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] | 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). | 0-36hrs post midazolam dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Midazolam Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | 0-36 hrs post midazolam dose | 
| Maximum Observed Plasma Midazolam Concentration (Cmax) |  | 0-36 hrs post midazolam dose | 
| Time to Reach Maximum Observed Plasma Midazolam Concentration (Tmax) |  | 0-36 hrs post midazolam dose | 
| Plasma Decay Half-Life (t1/2) of Midazolam | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 0-36 hrs post midazolam dose | 
| Minimum Observed Plasma Trough Concentration (Cmin) of PD-0332991 |  | Prior to the 6th, 7th, and 8th oral daily PD-0332991 dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PD-0332991, Midazolam, Drug-Drug Interaction Study, Healthy Adult Volunteer