A Phase 1 Absolute Bioavailability Study For Oral Crizotinib In Healthy Volunteers

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT01168934
• Date of registration: 22/07/2010
• Prospective Registration: Yes
• Primary sponsor: Pfizer
• Public title: A Phase 1 Absolute Bioavailability Study For Oral Crizotinib In Healthy Volunteers
• Scientific title: A Phase 1, Single Dose, Randomized, Cross-Over Absolute Bioavailability Study In Healthy Volunteers Comparing Oral To Intravenous Administration Of Crizotinib (PF-02341066)
• Date of first enrolment: August 2010
• Target sample size: 14
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01168934
• Study type: Interventional
• Phase: Phase 1

Countries of recruitment

Belgium

Contacts

• Name: Pfizer CT.gov Call Center
• Affiliation: Pfizer

Key inclusion & exclusion criteria

Inclusion Criteria:

- Healthy male and/or female of non-childbearing potential subjects between the ages of
18 and 55 years, inclusive (Healthy is defined as no clinically relevant abnormalities
identified by a detailed medical history, full physical examination, including blood
pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests).

- Body Mass Index (BMI) of 17.5 to 30.5 kg/m^2; 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 (including drug allergies, but excluding untreated, asymptomatic,
seasonal allergies at time of dosing).

- Any condition possibly affecting drug absorption (eg, gastrectomy).

- A positive urine drug screen.

- History of regular alcohol consumption exceeding 14 drinks/week for females or 21
drinks/week for males within 6 months of screening.

- Treatment with an investigational drug within 30 days (or as determined by the local
requirement, whichever is longer) or 5 half-lives preceding the first dose of study
medication.

- 12-lead ECG demonstrating QTc >450 msec at Screening.

- Pregnant or nursing females; females of childbearing potential, including those with
tubal ligation.

- Use of prescription or nonprescription drugs and dietary supplements within 7 days or
5 half-lives (whichever is longer) prior to the first dose of study medication. Herbal
supplements and hormone replacement therapy must be discontinued 28 days prior to the
first dose of study medication.

- Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or
investigational product administration or may interfere with the interpretation of
study results and, in the judgment of the investigator, would make the subject
inappropriate for entry into this study.

- A positive serology for Hepatitis B or Hepatitis C.

- Subjects who are currently smoking.



Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Healthy

Intervention(s)

Drug: crizotinib

Primary Outcome(s)

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - 8]) [Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B]

Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - 8][dn]) [Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hours (hrs) post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B]

Secondary Outcome(s)

Metabolite to Parent Ratio Area Under the Curve From Time Zero to Extrapolated Infinite Time (MRAUC [0-8]) [Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B]

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182) [Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B]

Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182) [Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B]

Apparent Oral Clearance (CL/F) [Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B]

Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182) [Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B]

Metabolite to Parent Ratio Maximum Observed Plasma Concentration (MRCmax) [Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B]

Volume of Distribution at Steady State (Vss) [Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A]

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B]

Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Last Quantifiable Concentration for Crizotinib Metabolite Ratio (MRAUClast) [Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B]

Time to Reach Maximum Observed Plasma Concentration (Tmax) [Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B]

Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) [Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B]

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - 8]) for Crizotinib Metabolite (PF-06260182) [Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B]

Plasma Decay Half Life (t1/2) [Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B]

Maximum Observed Plasma Concentration (Cmax) [Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B]

Apparent Volume of Distribution (Vz/F) [Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B]

Systemic Clearance (CL) [Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A]

Secondary ID(s)

A8081010

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 19/10/2011
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01168934