Clinical trial NCT01392703: Pharmacokinetic Study Comparing Blood Levels of Dasatinib in Healthy Participants Who Received the Tablet Formulation With Those Who Received Liquid and Tablet-dispersed Formulations
Official title: Open-label, Randomized, 3-period, 3-treatment Crossover, Bioequivalence Study Comparing Dasatinib (BMS-354825) Liquid Formulation and the Dispersed Tablet Formulation Relative to the Reference Tablet Formulation in Health Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetic Study in Healthy Participants
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2011-07-12
Enrollment: 141
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: The purpose of the study is to compare the blood levels of dasatinib in healthy participants who received tablet formulation with those of healthy participants who received liquid and tablet-dispersed formulations of the drug.


Eligibility criteria: Key Inclusion Criteria:

* Healthy participants, defined as having no clinically relevant deviation from normal in medical history, physical examination, electrocardiogram (ECG) findings, and clinical laboratory tests findings.
* Body mass index of 18 to 32 kg/m\^2, inclusive
* Age from 18 to 55 years
* Men and women who were not of childbearing potential (ie, who were postmenopausal or surgically sterile)
* All women must have had a negative serum or urine pregnancy test result(minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) at screening and within 24 hours prior to dosing with study drug
* Women must not have been breastfeeding
* Sexually active fertile men with female partners of childbearing potential were required to abide by the requirement to use effective birth control for the entire study and for 90 days after the date of last treatment
* Men must have agreed not to donate sperm for the entire study and for 90 days after the day of last study treatment
* Participants must have agreed not to make blood donations, including red blood cells, plasma, platelets, or whole blood, for the entire study and for 8 weeks after the day of last study treatment

Key Exclusion Criteria:

* Any significant acute or chronic medical illness
* Current or recent (within 3 months of study drug administration) disease of the gastrointestinal (GI) tract that may impact drug absorption and may affect pharmacokinetics of the study drugs or any GI tract surgery that may impact drug absorption
* Any major surgery, as determined by the investigator, within 4 weeks of dosing in Period 1
* Blood transfusion within 4 weeks of study drug administration
* Donation of \>400 mL of blood within 8 weeks prior to study dosing or donation of plasma within 4 weeks prior to study dosing
* Inability to tolerate oral medication
* Inability to tolerate orange juice
* Inability to undergo venipuncture and/or tolerate venous access
* Use of tobacco or nicotine-containing products within 6 months prior to check-in, or positive nicotine test at screening and/or check-in
* Consumption of more than 3 cups of coffee or other caffeine-containing products a day, or 5 cups of tea a day
* Recent (within 6 months of study drug administration) drug or alcohol abuse
* Positive blood screen for hepatitis C antibody; hepatitis B surface antigen; and HIV-1, HIV-2, or HIV antibody
* History of any significant drug allergy or asthma
* Evidence of organ dysfunction or any clinically relevant deviation from normal in physical examination, ECG findings, vital signs, or clinical laboratory test findings.
* Any of the following on 12-lead ECG prior to study drug administration, confirmed by repeat ECG:

  * PR ≥210 ms
  * QRS ≥120 ms
  * QT ≥500 ms
  * QTcF ≥450 ms

Primary outcomes:
measure: Maximum Observed Concentration (Cmax) of Dasatinib
timeFrame: Days 1-2, Days 5-6, and Days 9-10
measure: Area Under the Plasma Concentration-time Curve From Zero to the Last Time of the Last Quantifiable Concentration (AUC[0-T])of Dasatinib
timeFrame: Days 1-2, Days 5-6, and Days 9-10
measure: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0-INF]) of Dasatinib
timeFrame: Days 1-2, Days 5-6, and Days 9-10
Secondary outcomes:
measure: Time of Maximum Observed Plasma Concentration (Tmax) of Dasatinib
timeFrame: Days 1-2, Days 5-6, and Days 9-10
measure: Half-life of Dasatinib
timeFrame: Days 1-2, Days 5-6, and Days 9-10
measure: Number of Participants With at Least 1 Adverse Event (AE), With at Least 1 Treatment-related AE, Who Discontinued Due to AEs, and With at Least 1 Serious Adverse Event (SAE)
timeFrame: Continually from enrollment through Day 9 and at study discharge on Day 10
measure: Number of Participants With Clinically Significant Changes in Vital Signs or Electrocardiogram (ECG) Findings
timeFrame: Day -1, Screening, and Days 1, 5, 9 and 10 (at study discharge)
measure: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests
timeFrame: Day -1, Screening, and Day 9 of current treatment regimen
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Healthcare Discoveries Inc.
state: Texas
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: