A Study To Evaluate The Effect Of Rifampin On Pharmacokinetics Of PF-06463922 In Healthy Volunteers

NCT02804399 | Completed Phase 1 Results

• 2 other identifiers: B7461011RIFAMPIN DDI STUDY
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Keywords

rifampin; pharmacokinetics; PF-06463922; drug interaction

Outcome Measures

Primary Outcomes (2)

• Plasma AUCinf for PF-06463922 Given Alone and With Rifampin

  AUCinf is the plasma area under the plasma concentration-time profile from time 0 extrapolated to infinite time. The pharmacokinetics (PK) parameter analysis population was defined as all participants enrolled and treated who have at least 1 of the PF-06463922 PK parameters of primary interest in at least 1 treatment period.

  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.

• Plasma Cmax for PF-06463922 Given Alone and With Rifampin

  Cmax is the maximum observed plasma concentration. PK parameter analysis population was defined as all participants enrolled and treated who have at least 1 of the PF-06463922 PK parameters of primary interest in at least 1 treatment period.

  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 (13)

• Plasma AUClast for PF-06463922 Given Alone and With Rifampin

  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.

• Plasma Tmax for PF-06463922 Given Alone and With Rifampin

  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.

• Plasma t1/2 for PF-06463922 Given Alone and With Rifampin

  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.

• Plasma CL/F for PF-06463922 Given Alone and With Rifampin

  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.

• Plasma Vz/F for PF-06463922 Given Alone and With Rifampin

  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.

Other Outcomes (6)

• Number of Participants With End of Study Abnormal Laboratory Findings Meeting the Criteria of Potentially Significant Clinical Concern

  Baseline to about 18 days after the first PF-06463922 dose

• Number of Participants With Physical Examination Findings Meeting the Criteria of Potentially Significant Clinical Concern

  Baseline to about 18 days after the first PF-06463922 dose.

• Number of Participants With Changes From Baseline and Absolute Values in Vital Signs Meeting the Criteria of Potentially Significant Clinical Concerns

  Baseline to about 18 days after the first PF-06463922 dose.

Study Arms (1)

all subjects

EXPERIMENTAL

subjects will receive a 100 mg single oral dose of PF-06463922 followed by a 100 mg single dose of PF-06463922 combined with 600 mg QD dose of rifampin with at least 10 days of washout period between two PF-06463922 doses.

Drug: PF-06463922; Drug: rifampin

Interventions

PF-06463922 DRUG

100 mg oral dose on day 1 in period 1 and on day 8 in period 2

Also known as: lorlatinib

all subjects

rifampin DRUG

600 mg QD from day 1 to day 12 in period 2.

Also known as: rifampicin

all subjects

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Pfizer New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

Location

Related Publications (1)

• 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.

  PMID: 31863284 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

lorlatinib; Rifampin

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Limitations and Caveats

As all participants receiving co-administration of PF-06463922 (100 mg SD) with rifampin (600 mg QD) experienced drug-induced liver injury AEs, all 12 participants were discontinued from further rifampin treatment after 9 days but not 12 days.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

001800781021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2016
• First Posted: June 17, 2016
• Study Start: July 1, 2016
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: January 25, 2019
• Results First Posted: January 25, 2019

Record last verified: 2018-08

Locations

US (1)