A Study to Determine the Effect of Food on the Pharmacokinetics of PCI-32765
Open-Label, Randomized, 4-Way Crossover Study to Determine the Effect of Food on the Pharmacokinetics of PCI-32765
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Detailed Description
Study Type
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Phase 1
Contacts and Locations
Study Locations
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New Jersey
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Neptune, New Jersey, United States
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-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Women must be postmenopausal or documented as surgically sterile
- Men must agree to use an adequate contraception method as deemed appropriate by the investigator during the study and for 3 months after receiving the last dose of study drug, and to not donate sperm during the study and for 3 months after receiving the last dose of study drug
- Body mass index between 18 and 30 kg/m2and body weight not less than 50 kg
- Blood pressure (after sitting for 5 minutes) between 90 and 140 mmHg systolic, inclusive, and no higher than 90 mmHg diastolic
Exclusion Criteria:
- History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, neurologic or psychiatric disease, infection, history of immune disorders (eg, lupus, rheumatoid arthritis, psoriatic arthritis) or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results
- Clinically significant abnormal values for hematology, coagulation, PFA-100, clinical chemistry or urinalysis at screening
- Clinically significant abnormal physical examination, vital signs or 12 lead electrocardiogram (ECG) at screening
- Use of aspirin, non-steroidal anti-inflammatory agents, clopidogrel, Vitamin E supplements, fish oil, or flax seed within 1 week before PFA-100 assay test at screening
- Use of any prescription or nonprescription medication (including vitamins and herbal supplements), except for acetaminophen, and hormonal replacement therapy, within 14 days before the first dose of the study drug is scheduled
- Use of herbal supplements (such as St. John's Wort) within 30 days of the first dose administration
- Has a history of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (4th edition) (DSM-IV) criteria within 2 years before screening or positive test result(s) for alcohol and/or drugs of abuse (such as barbiturates, opiates, cocaine, cannabinoids, amphetamines and benzodiazepines) at screening and Day -1 of each treatment period
- History of clinically significant allergies, especially known hypersensitivity or intolerance to sulfonamide or beta-lactam antibiotics
- Known allergy to the study drug or any of the excipients of the formulation
- Known allergy to heparin or history of heparin induced thrombocytopenia
- Donated blood or blood products or had substantial loss of blood within 3 months before the first administration of study drug or intention to donate blood or blood products during the study
- Received an experimental drug or used an experimental medical device within 1 month or within a period less than 10 times the drug's half life, whichever is longer, before the first dose of the study drug is scheduled
- Unable to swallow solid, oral dosage forms whole with the aid of water (participants may not chew, divide, dissolve, or crush the study drug)
- Positive test for human immunodeficiency virus (HIV) 1 and 2 antibodies, hepatitis B surface antigen (HBsAg), or hepatitis C antibodies
- History of smoking or use of nicotine-containing substances within the previous 2 months, as determined by medical history or participant's verbal report and confirmed by cotinine test
- Preplanned surgery or procedures that would interfere with the conduct of the study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Experimental: Treatment A: PCI-32765
420 mg capsules administered by mouth with 240 mL noncarbonated water 30 minutes after completing a high-fat breakfast
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Period 1 = Treatment D, Period 2 = Treatment C, Period 3 = Treatment A, Period 4 = Treatment B
Period 1 = Treatment A, Period 2 = Treatment D, Period 3 = Treatment B, Period 4 = Treatment C
Period 1 = Treatment B, Period 2 = Treatment A, Period 3 = Treatment C, Period 4 = Treatment D
Period 1 = Treatment C, Period 2 = Treatment B, Period 3 = Treatment D, Period 4 = Treatment A
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|
Experimental: Treatment B: PCI-32765
420 mg capsules administered by mouth with 240 mL noncarbonated water after fasting for at least 10 hours and 30 minutes before starting a high-fat breakfast
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Period 1 = Treatment D, Period 2 = Treatment C, Period 3 = Treatment A, Period 4 = Treatment B
Period 1 = Treatment A, Period 2 = Treatment D, Period 3 = Treatment B, Period 4 = Treatment C
Period 1 = Treatment B, Period 2 = Treatment A, Period 3 = Treatment C, Period 4 = Treatment D
Period 1 = Treatment C, Period 2 = Treatment B, Period 3 = Treatment D, Period 4 = Treatment A
|
|
Experimental: Treatment C: PCI-32765
420 mg capsules administered by mouth with 240 mL noncarbonated water 2 hours after completing a high-fat breakfast
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Period 1 = Treatment D, Period 2 = Treatment C, Period 3 = Treatment A, Period 4 = Treatment B
Period 1 = Treatment A, Period 2 = Treatment D, Period 3 = Treatment B, Period 4 = Treatment C
Period 1 = Treatment B, Period 2 = Treatment A, Period 3 = Treatment C, Period 4 = Treatment D
Period 1 = Treatment C, Period 2 = Treatment B, Period 3 = Treatment D, Period 4 = Treatment A
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Experimental: Treatment D: PCI-32765
420 mg capsules administered with 240 mL noncarbonated water after fasting at least 10 hours
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Period 1 = Treatment D, Period 2 = Treatment C, Period 3 = Treatment A, Period 4 = Treatment B
Period 1 = Treatment A, Period 2 = Treatment D, Period 3 = Treatment B, Period 4 = Treatment C
Period 1 = Treatment B, Period 2 = Treatment A, Period 3 = Treatment C, Period 4 = Treatment D
Period 1 = Treatment C, Period 2 = Treatment B, Period 3 = Treatment D, Period 4 = Treatment A
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Experimental: Treatment E: PCI-32765
840 mg capsules administered with 240mL noncarbonated water 30 minutes after completing a high-fat breakfast
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After completion of the 4-way crossover, an additional separate cohort of 8 subjects were enrolled.
These subjects participated in 1 treatment period to document safety and PK
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What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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Area under the plasma concentration-time curve from time 0 to time the last quantifiable concentrations of PCI-32765
Time Frame: Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
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Area under the plasma concentration-time curve from time 0 to infinite time of PCI-32765
Time Frame: Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
|
Maximum plasma concentration of PCI-32765
Time Frame: Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
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Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
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Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Time to reach the maximum plasma concentration of PCI-32765
Time Frame: Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
|
|
Percentage of area under the plasma concentration-time curve from time 0 to infinite time obtained by extrapolation of PCI-32765
Time Frame: Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
|
|
Elimination half-life of PCI-32765
Time Frame: Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
|
|
Relative bioavailability of PCI-32765
Time Frame: Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
Relative bioavailability is defined as the ratio of the area under the concentration curve to infinity between the test treatment and the reference treatment.
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Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
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Maximum plasma concentration of metabolite PCI-45227
Time Frame: Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
|
|
Time to reach the maximum plasma concentration of metabolite PCI-45227
Time Frame: Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
|
|
Area under the plasma concentration-time curve from time 0 to time the last quantifiable concentrations of metabolite PCI-45227
Time Frame: Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
|
|
Area under the plasma concentration-time curve from time 0 to infinite time of metabolite PCI-45227
Time Frame: Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
|
|
Percentage of area under the plasma concentration-time curve from time 0 to infinite time obtained by extrapolation of metabolite PCI-45227
Time Frame: Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
|
|
Elimination half-life of metabolite PCI-45227
Time Frame: Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
|
|
Relative bioavailability of metabolite PCI-45227
Time Frame: Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
Predose; postdose at 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours
|
|
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Number of participants with adverse events
Time Frame: Up to 30 days following the last dose of study drug
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Up to 30 days following the last dose of study drug
|
|
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Number of participants with adverse events of special interest (major hemorrhage and intracranial hemorrhage)
Time Frame: Up to 30 days following the last dose of study drug
|
Up to 30 days following the last dose of study drug
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Collaborators and Investigators
Sponsor
Sponsor
Collaborators
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Study Start
Primary Completion (Actual)
Primary Completion
Study Completion (Actual)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Estimate)
First Posted
Study Record Updates
Last Update Posted (Estimate)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
Other Study ID Numbers
- CR101204
- PCI-32765CLL1001 (Other Identifier: Janssen Research & Development, LLC)
- 2013-000963-96 (EudraCT Number)
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