Pharmacokinetic Study Comparing Blood Levels of Dasatinib in Healthy Participants Who Received the Tablet Formulation With Those Who Received Liquid and Tablet-dispersed Formulations

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

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.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetic Study in Healthy Participants
• Intervention / Treatment: Drug: Dasatinib as tablets; Drug: Dasatinib as liquid; Drug: Dasatinib as dispersed tablets

• Study Type: Interventional
• Enrollment (Actual): 141
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78209
      • Healthcare Discoveries Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Dasatinib, 100 mg as tablets + water; Treatment A. Participants were randomized to and received treatment in 1 of 6 sequences (ABC, ACB, BCA, BAC, CAB, or CBA), administered over 3 1-day treatment periods (Days 1, 5, and 9), with treatment changing to next in the sequence at start of each new period. A 3-day washout period followed treatment periods 1 and 2.	Drug: Dasatinib as tablets; 2 50-mg tablets plus 240 mL noncarbonated, nonrefrigerated water. Oral, single dose, 1 day; Other Names: Dasatinib/BMS-354825
Other: Dasatinib, 100 mg as liquid + water; Treatment B. Participants were randomized to and received treatment in 1 of 6 sequences (ABC, ACB, BCA, BAC, CAB, or CBA), administered over 3 1-day treatment periods (Days 1, 5, and 9), with treatment changing to next in the sequence at start of each new period. A 3-day washout period followed treatment periods 1 and 2.	Drug: Dasatinib as liquid; 100 mg administered as 10 mL of liquid drug (10 mg/mL) plus 230 mL noncarbonated, nonrefrigerated water. Oral, single dose, 1 day; Other Names: Dasatinib/BMS-354825
Other: Dasatinib, 100 mg as tablets in orange juice + water; Treatment C. Participants were randomized to and received treatment in 1 of 6 sequences (ABC, ACB, BCA, BAC, CAB, or CBA), administered over 3 1-day treatment periods (Days 1, 5, and 9), with treatment changing to next in the sequence at start of each new period. A 3-day washout period followed treatment periods 1 and 2.	Drug: Dasatinib as dispersed tablets; 2 50-mg dispersed tablets in 30 mL of 100% orange juice followed by 15 mL of orange juice plus 195 mL noncarbonated, nonrefrigerated water. Liquid (oral solution), single dose, 1 day.; Other Names: Dasatinib/BMS-354825

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Concentration (Cmax) of Dasatinib	Single-dose pharmacokinetic parameters, including Cmax, were derived using noncompartmental methods from plasma dasatinib concentration-time data.	Days 1-2, Days 5-6, and Days 9-10
Area Under the Plasma Concentration-time Curve From Zero to the Last Time of the Last Quantifiable Concentration (AUC[0-T])of Dasatinib	Single-dose pharmacokinetic, such as AUC(0-T),parameters were derived using noncompartmental methods from plasma dasatinib concentration-time data.	Days 1-2, Days 5-6, and Days 9-10
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0-INF]) of Dasatinib	Single-dose pharmacokinetic parameters, such as AUC(0-INF) were derived using noncompartmental methods from plasma dasatinib concentration-time data.	Days 1-2, Days 5-6, and Days 9-10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of Maximum Observed Plasma Concentration (Tmax) of Dasatinib	Single-dose pharmacokinetic parameters, such as Tmax, were derived using noncompartmental methods from plasma dasatinib concentration-time data.	Days 1-2, Days 5-6, and Days 9-10
Half-life of Dasatinib		Days 1-2, Days 5-6, and Days 9-10
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)	An AE is any new untoward medical occurrence or worsening of a preexisting medical condition in a patient or clinical investigation participant who has received an investigational (medicinal) product that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of investigational product, whether or not considered related to the investigational product. An SAE is an untoward medical event that at any dose results in death, persistent or significant disability/incapacity; is life-threatening or a congenital anomaly/birth defect; or requires or prolongs hospitalization; is an important medical event that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention.	Continually from enrollment through Day 9 and at study discharge on Day 10
Number of Participants With Clinically Significant Changes in Vital Signs or Electrocardiogram (ECG) Findings	Blood pressure and heart rate were measured after the participant had been seated quietly for at least 5 minutes. ECG findings were recorded after the participant had been supine for at least 5 minutes. Clinically significant as reported by principal investigator.	Day -1, Screening, and Days 1, 5, 9 and 10 (at study discharge)
Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests	Criteria for normal: bilirubin (0.2 to 1.3 mg/dL); lactate dehydrogenase (101 to 227 U/L); eosinophils (0.06 to 0.87*103 c/μL); erythrocytes (4.2 to 5.8*10^6 c/μL). Participants were required to fast for a minimum of 4 hours prior to the collection of specimens for clinical laboratory tests at screening and for at least 8 hours prior to collection on Day -1. Marked abnormalities were reported for the treatment regiment that participants received just prior to clinical laboratory testing.	Day -1, Screening, and Day 9 of current treatment regimen

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: July 11, 2011
• First Submitted That Met QC Criteria: July 11, 2011
• First Posted (Estimate): July 12, 2011

Study Record Updates

• Last Update Posted (Estimate): February 11, 2013
• Last Update Submitted That Met QC Criteria: January 4, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Dasatinib
• Other Study ID Numbers: CA180-352