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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.

Phase 1
Completed
Conditions
Healthy
Interventions
Registration Number
NCT01756781
Lead Sponsor
Pfizer
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
26
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Sequence 1PD-0332991Subjects 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.
Sequence 2PD-0332991Subjects 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.
Sequence 1MidazolamSubjects 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.
Sequence 2MidazolamSubjects 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.
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
Plasma Decay Half-Life (t1/2) of Midazolam0-36 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-0332991Prior to the 6th, 7th, and 8th oral daily PD-0332991 dose
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

Trial Locations

Locations (1)

Pfizer Investigational Site

🇺🇸

South Miami, Florida, United States

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