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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01392703
First received: July 11, 2011
Last updated: January 4, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Pharmacokinetic Study in Healthy Participants
Drug: Dasatinib as tablets
Drug: Dasatinib as liquid
Drug: Dasatinib as dispersed tablets
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Maximum Observed Concentration (Cmax) of Dasatinib [ Time Frame: Days 1-2, Days 5-6, and Days 9-10 ] [ Designated as safety issue: No ]
    Single-dose pharmacokinetic parameters, including Cmax, were derived using noncompartmental methods from plasma dasatinib concentration-time data.

  • Area Under the Plasma Concentration-time Curve From Zero to the Last Time of the Last Quantifiable Concentration (AUC[0-T])of Dasatinib [ Time Frame: Days 1-2, Days 5-6, and Days 9-10 ] [ Designated as safety issue: No ]
    Single-dose pharmacokinetic, such as AUC(0-T),parameters were derived using noncompartmental methods from plasma dasatinib concentration-time data.

  • Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0-INF]) of Dasatinib [ Time Frame: Days 1-2, Days 5-6, and Days 9-10 ] [ Designated as safety issue: No ]
    Single-dose pharmacokinetic parameters, such as AUC(0-INF) were derived using noncompartmental methods from plasma dasatinib concentration-time data.


Secondary Outcome Measures:
  • Time of Maximum Observed Plasma Concentration (Tmax) of Dasatinib [ Time Frame: Days 1-2, Days 5-6, and Days 9-10 ] [ Designated as safety issue: No ]
    Single-dose pharmacokinetic parameters, such as Tmax, were derived using noncompartmental methods from plasma dasatinib concentration-time data.

  • Half-life of Dasatinib [ Time Frame: Days 1-2, Days 5-6, and Days 9-10 ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: Continually from enrollment through Day 9 and at study discharge on Day 10 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Clinically Significant Changes in Vital Signs or Electrocardiogram (ECG) Findings [ Time Frame: Day -1, Screening, and Days 1, 5, 9 and 10 (at study discharge) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests [ Time Frame: Day -1, Screening, and Day 9 of current treatment regimen ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 141
Study Start Date: July 2011
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Dasatinib/BMS-354825
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 Name: Dasatinib/BMS-354825
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 Name: Dasatinib/BMS-354825

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01392703

Locations
United States, Texas
Healthcare Discoveries Inc.
San Antonio, Texas, United States, 78209
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01392703     History of Changes
Other Study ID Numbers: CA180-352
Study First Received: July 11, 2011
Results First Received: November 5, 2012
Last Updated: January 4, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Dasatinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014