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.

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT01756781

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Midazolam Drug: PD-0332991 Drug: Midazolam Drug: PD-0332991	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

26 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Study Start Date :

May 1, 2013

Actual Primary Completion Date :

Jul 1, 2013

Actual Study Completion Date :

Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sequence 1 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 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. Drug: PD-0332991 Treatment B includes 8 daily 125 mg oral doses of PD-0332991.
Experimental: Sequence 2 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 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. Drug: PD-0332991 Treatment B is made up of 8 daily 125 mg oral doses of PD-0332991.

Arm

Intervention/Treatment

Experimental: Sequence 1

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

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.

Drug: PD-0332991

Treatment B includes 8 daily 125 mg oral doses of PD-0332991.

Experimental: Sequence 2

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

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.

Drug: PD-0332991

Treatment B is made up of 8 daily 125 mg oral doses of PD-0332991.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Midazolam Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [0-36 hrs post midazolam dose]
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
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 [0-36 hrs post midazolam dose]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Minimum Observed Plasma Trough Concentration (Cmin) of PD-0332991 [Prior to the 6th, 7th, and 8th oral daily PD-0332991 dose]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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.