Clinical trial NCT02804399: A Study To Evaluate The Effect Of Rifampin On Pharmacokinetics Of PF-06463922 In Healthy Volunteers
Official title: A Phase One, Open Label, Two-period, Two-treatment, Fixed Sequence, Cross-over Study To Estimate The Effect Of Multiple Dose Rifampin On The Single Dose Pharmacokinetics Of Pf-06463922 In Healthy Volunteers.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: rifampin
pharmacokinetics
PF-06463922
drug interaction
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2016-06-17
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The purpose of this study is to estimate the effect of rifampin on the single dose PK of PF-06463922.

Detailed description: This will be a Phase 1, open-label, 2-period, 2-treatment, fixed-sequence, cross-over study in approximately 12 healthy subjects employing administration of a single oral dose of PF-06463922 in the fasted state alone, and with multiple dosing of rifampin 600 mg once a day to estimate the effect of multiple dose rifampin on the single dose PK of PF-06463922.

Eligibility criteria: Inclusion Criteria:

* Healthy female subjects of non-childbearing potential and/or male subjects who, at the time of screening, are between the ages of 18 and 55 years, inclusive
* Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lbs)

Exclusion Criteria:

* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease
* Any condition possibly affecting drug absorption
* Positive urine drug screen
* History of HIV, Hep B or Hep C
* History of regular alcohol consumption
* History of cardiac arrhythmia, history of AV block, history of symptomatic bradycardia, history of QTc prolongation
* History of pancreatitis or hyperlipidemia, elevated lipase

Primary outcomes:
measure: Plasma AUCinf for PF-06463922 Given Alone and With Rifampin
timeFrame: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.
measure: Plasma Cmax for PF-06463922 Given Alone and With Rifampin
timeFrame: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.
Secondary outcomes:
measure: Plasma AUClast for PF-06463922 Given Alone and With Rifampin
timeFrame: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.
measure: Plasma Tmax for PF-06463922 Given Alone and With Rifampin
timeFrame: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.
measure: Plasma t1/2 for PF-06463922 Given Alone and With Rifampin
timeFrame: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.
measure: Plasma CL/F for PF-06463922 Given Alone and With Rifampin
timeFrame: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.
measure: Plasma Vz/F for PF-06463922 Given Alone and With Rifampin
timeFrame: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg administration with rifampin in Period 2.
measure: Plasma AUClast for PF-06895751 When PF-06463922 Given Alone and With Rifampin
timeFrame: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.
measure: Plasma AUCinf for PF-06895751 When PF-06463922 Given Alone and With Rifampin
timeFrame: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.
measure: Plasma Tmax for PF-06895751 When PF-06463922 Given Alone and With Rifampin.
timeFrame: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.
measure: Plasma t1/2 for PF-06895751 When PF-06463922 Given Alone and With Rifampin
timeFrame: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.
measure: Plasma Cmax for PF-06895751 When PF-06463922 Given Alone and With Rifampin
timeFrame: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.
measure: Plasma Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for Cmax (MRCmax) of PF-06463922 and Its Metabolite: When PF-06463922 Given Alone and With Rifampin
timeFrame: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.
measure: Plasma Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for AUClast (MRAUClast) of PF-06463922 and Its Metabolite: When PF-06463922 Given Alone and With Rifampin
timeFrame: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.
measure: Plasma Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for AUCinf (MRAUCinf) of PF-06463922 and Its Metabolite: When PF-06463922 Given Alone and With Rifampin
timeFrame: Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2.
Other outcomes:
measure: Number of Participants With End of Study Abnormal Laboratory Findings Meeting the Criteria of Potentially Significant Clinical Concern
timeFrame: Baseline to about 18 days after the first PF-06463922 dose
measure: Number of Participants With Physical Examination Findings Meeting the Criteria of Potentially Significant Clinical Concern
timeFrame: Baseline to about 18 days after the first PF-06463922 dose.
measure: Number of Participants With Changes From Baseline and Absolute Values in Vital Signs Meeting the Criteria of Potentially Significant Clinical Concerns
timeFrame: Baseline to about 18 days after the first PF-06463922 dose.
measure: Number of Participants With Electrocardiogram (ECG) Findings Meeting the Criteria of Potentially Significant Clinical Concerns
timeFrame: Baseline to about 18 days after the first PF-06463922 dose.
measure: Number of Participants With Concomitant Treatments Meeting the Criteria of Potentially Significant Clinical Concerns
timeFrame: Baseline to about 18 days after the first PF-06463922 dose.
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities and Treatment-Related)
timeFrame: Baseline to about 18 days after the first PF-06463922 dose.
Locations:
city: New Haven
country: United States
facility: Pfizer New Haven Clinical Research Unit
state: Connecticut
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Chen J, Xu H, Pawlak S, James LP, Peltz G, Lee K, Ginman K, Bergeron M, Pithavala YK. The Effect of Rifampin on the Pharmacokinetics and Safety of Lorlatinib: Results of a Phase One, Open-Label, Crossover Study in Healthy Participants. Adv Ther. 2020 Feb;37(2):745-758. doi: 10.1007/s12325-019-01198-9. Epub 2019 Dec 20.