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:
Bristol-Myers Squibb
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
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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:
MedlinePlus related topics:
Drinking Water
Drug Information available for:
Dasatinib
U.S. FDA Resources
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 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 May 19, 2013