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.

October 6, 2015 updated by: Pfizer

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

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.

Study Overview

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Florida
      • South Miami, Florida, United States, 33143
        • Pfizer Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

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.

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

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.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Midazolam Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)]
Time Frame: 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).
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)
Time Frame: 0-36 hrs post midazolam dose
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)
Time Frame: 0-36 hrs post midazolam dose
0-36 hrs post midazolam dose
Time to Reach Maximum Observed Plasma Midazolam Concentration (Tmax)
Time Frame: 0-36 hrs post midazolam dose
0-36 hrs post midazolam dose
Plasma Decay Half-Life (t1/2) of Midazolam
Time Frame: 0-36 hrs post midazolam dose
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
Time Frame: Prior to the 6th, 7th, and 8th oral daily PD-0332991 dose
Prior to the 6th, 7th, and 8th oral daily PD-0332991 dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2013

Primary Completion (Actual)

July 1, 2013

Study Completion (Actual)

July 1, 2013

Study Registration Dates

First Submitted

December 20, 2012

First Submitted That Met QC Criteria

December 26, 2012

First Posted (Estimate)

December 27, 2012

Study Record Updates

Last Update Posted (Estimate)

October 8, 2015

Last Update Submitted That Met QC Criteria

October 6, 2015

Last Verified

October 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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