Trial Outcomes & Findings for Pharmacokinetic Study Comparing Blood Levels of Dasatinib in Healthy Participants Who Received the Tablet Formulation With Those Who Received Liquid and Tablet-dispersed Formulations (NCT NCT01392703)
NCT ID: NCT01392703
Last Updated: 2013-02-11
Results Overview
Single-dose pharmacokinetic parameters, including Cmax, were derived using noncompartmental methods from plasma dasatinib concentration-time data.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
141 participants
Primary outcome timeframe
Days 1-2, Days 5-6, and Days 9-10
Results posted on
2013-02-11
Participant Flow
A total of 141 participants were enrolled, of which 78 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.
Participant milestones
| Measure |
Dasatinib, 100 mg as Tablets + Water
Treatment A: Participants received a single oral dose of dasatinib, 100 mg, administered as 2 50-mg tablets, plus 240 mL of noncarbonated, nonrefrigerated water. All doses were administered in the fasted state. A 3-day washout period followed the treatment period.
|
Dasatinib, 100 mg as Liquid + Water
Treatment B: Participants received a single oral dose of dasatinib, 100 mg, administered as 10 mL of reconstituted suspension of dasatinib powder for oral suspension (10 mg dasatinib/mL) with 230 mL of noncarbonated, nonrefrigerated water. All doses were administered in the fasted state. A 3-day washout period followed the treatment period.
|
Dasatinib, 100 mg as Tablets in Orange Juice + Water
Treatment C: Participants received a single oral dose of dasatinib, 100 mg, administered as 2 50-mg tablets dispersed in 30 mL of 100% orange juice, followed by 15 mL of orange juice as a rinsing solution plus 195 mL noncarbonated, nonrefrigerated water. All doses were administered in the fasted state.
|
|---|---|---|---|
|
Day 1
STARTED
|
26
|
26
|
26
|
|
Day 1
COMPLETED
|
26
|
26
|
26
|
|
Day 1
NOT COMPLETED
|
0
|
0
|
0
|
|
Day 5
STARTED
|
26
|
25
|
26
|
|
Day 5
COMPLETED
|
26
|
25
|
26
|
|
Day 5
NOT COMPLETED
|
0
|
0
|
0
|
|
Day 9
STARTED
|
26
|
26
|
25
|
|
Day 9
COMPLETED
|
26
|
26
|
25
|
|
Day 9
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetic Study Comparing Blood Levels of Dasatinib in Healthy Participants Who Received the Tablet Formulation With Those Who Received Liquid and Tablet-dispersed Formulations
Baseline characteristics by cohort
| Measure |
All Treated
n=78 Participants
|
|---|---|
|
Age Continuous
|
36.5 years
STANDARD_DEVIATION 8.75 • n=99 Participants
|
|
Age, Customized
Younger than 65 years
|
78 Participants
n=99 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
71 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Hispanic/Latino
|
39 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic/Latino
|
39 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Days 1-2, Days 5-6, and Days 9-10Population: All participants who received at least 1 dose of any study drug and had pharmacokinetic data available.
Single-dose pharmacokinetic parameters, including Cmax, were derived using noncompartmental methods from plasma dasatinib concentration-time data.
Outcome measures
| Measure |
Dasatinib, 100 mg as Tablets + Water
n=78 Participants
Treatment A: Participants received a single oral dose of dasatinib, 100 mg, administered as 2 50-mg tablets, plus 240 mL of noncarbonated, nonrefrigerated water. All doses were administered in the fasted state. A 3-day washout period followed the treatment period.
|
Dasatinib, 100 mg as Liquid + Water
n=77 Participants
Treatment B: Participants received a single oral dose of dasatinib, 100 mg, administered as 10 mL of reconstituted suspension of dasatinib powder for oral suspension (10 mg dasatinib/mL) with 230 mL of noncarbonated, nonrefrigerated water. All doses were administered in the fasted state. A 3-day washout period followed the treatment period.
|
Dasatinib, 100 mg as Tablets in Orange Juice + Water
n=77 Participants
Treatment C: Participants received a single oral dose of dasatinib, 100 mg, administered as 2 50-mg tablets dispersed in 30 mL of 100% orange juice, followed by 15 mL of orange juice as a rinsing solution plus 195 mL noncarbonated, nonrefrigerated water. All doses were administered in the fasted state.
|
|---|---|---|---|
|
Maximum Observed Concentration (Cmax) of Dasatinib
|
114 ng/mL
Geometric Coefficient of Variation 51
|
106 ng/mL
Geometric Coefficient of Variation 53
|
110 ng/mL
Geometric Coefficient of Variation 50
|
PRIMARY outcome
Timeframe: Days 1-2, Days 5-6, and Days 9-10Population: All participants who received at least 1 dose of any study drug and had pharmacokinetic data available.
Single-dose pharmacokinetic, such as AUC(0-T),parameters were derived using noncompartmental methods from plasma dasatinib concentration-time data.
Outcome measures
| Measure |
Dasatinib, 100 mg as Tablets + Water
n=78 Participants
Treatment A: Participants received a single oral dose of dasatinib, 100 mg, administered as 2 50-mg tablets, plus 240 mL of noncarbonated, nonrefrigerated water. All doses were administered in the fasted state. A 3-day washout period followed the treatment period.
|
Dasatinib, 100 mg as Liquid + Water
n=77 Participants
Treatment B: Participants received a single oral dose of dasatinib, 100 mg, administered as 10 mL of reconstituted suspension of dasatinib powder for oral suspension (10 mg dasatinib/mL) with 230 mL of noncarbonated, nonrefrigerated water. All doses were administered in the fasted state. A 3-day washout period followed the treatment period.
|
Dasatinib, 100 mg as Tablets in Orange Juice + Water
n=77 Participants
Treatment C: Participants received a single oral dose of dasatinib, 100 mg, administered as 2 50-mg tablets dispersed in 30 mL of 100% orange juice, followed by 15 mL of orange juice as a rinsing solution plus 195 mL noncarbonated, nonrefrigerated water. All doses were administered in the fasted state.
|
|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Zero to the Last Time of the Last Quantifiable Concentration (AUC[0-T])of Dasatinib
|
374 ng*h/mL
Geometric Coefficient of Variation 45
|
327 ng*h/mL
Geometric Coefficient of Variation 44
|
342 ng*h/mL
Geometric Coefficient of Variation 42
|
PRIMARY outcome
Timeframe: Days 1-2, Days 5-6, and Days 9-10Population: All participants who received at least 1 dose of any study drug and had pharmacokinetic data available.
Single-dose pharmacokinetic parameters, such as AUC(0-INF) were derived using noncompartmental methods from plasma dasatinib concentration-time data.
Outcome measures
| Measure |
Dasatinib, 100 mg as Tablets + Water
n=75 Participants
Treatment A: Participants received a single oral dose of dasatinib, 100 mg, administered as 2 50-mg tablets, plus 240 mL of noncarbonated, nonrefrigerated water. All doses were administered in the fasted state. A 3-day washout period followed the treatment period.
|
Dasatinib, 100 mg as Liquid + Water
n=77 Participants
Treatment B: Participants received a single oral dose of dasatinib, 100 mg, administered as 10 mL of reconstituted suspension of dasatinib powder for oral suspension (10 mg dasatinib/mL) with 230 mL of noncarbonated, nonrefrigerated water. All doses were administered in the fasted state. A 3-day washout period followed the treatment period.
|
Dasatinib, 100 mg as Tablets in Orange Juice + Water
n=77 Participants
Treatment C: Participants received a single oral dose of dasatinib, 100 mg, administered as 2 50-mg tablets dispersed in 30 mL of 100% orange juice, followed by 15 mL of orange juice as a rinsing solution plus 195 mL noncarbonated, nonrefrigerated water. All doses were administered in the fasted state.
|
|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0-INF]) of Dasatinib
|
429 ng*h/mL
Geometric Coefficient of Variation 39
|
338 ng*h/mL
Geometric Coefficient of Variation 43
|
353 ng*h/mL
Geometric Coefficient of Variation 41
|
SECONDARY outcome
Timeframe: Days 1-2, Days 5-6, and Days 9-10Population: All participants who received at least 1 dose of any study drug and had pharmacokinetic data available.
Single-dose pharmacokinetic parameters, such as Tmax, were derived using noncompartmental methods from plasma dasatinib concentration-time data.
Outcome measures
| Measure |
Dasatinib, 100 mg as Tablets + Water
n=78 Participants
Treatment A: Participants received a single oral dose of dasatinib, 100 mg, administered as 2 50-mg tablets, plus 240 mL of noncarbonated, nonrefrigerated water. All doses were administered in the fasted state. A 3-day washout period followed the treatment period.
|
Dasatinib, 100 mg as Liquid + Water
n=77 Participants
Treatment B: Participants received a single oral dose of dasatinib, 100 mg, administered as 10 mL of reconstituted suspension of dasatinib powder for oral suspension (10 mg dasatinib/mL) with 230 mL of noncarbonated, nonrefrigerated water. All doses were administered in the fasted state. A 3-day washout period followed the treatment period.
|
Dasatinib, 100 mg as Tablets in Orange Juice + Water
n=77 Participants
Treatment C: Participants received a single oral dose of dasatinib, 100 mg, administered as 2 50-mg tablets dispersed in 30 mL of 100% orange juice, followed by 15 mL of orange juice as a rinsing solution plus 195 mL noncarbonated, nonrefrigerated water. All doses were administered in the fasted state.
|
|---|---|---|---|
|
Time of Maximum Observed Plasma Concentration (Tmax) of Dasatinib
|
1.00 Hours
Interval 0.25 to 3.0
|
0.53 Hours
Interval 0.5 to 3.0
|
0.50 Hours
Interval 0.5 to 4.0
|
SECONDARY outcome
Timeframe: Days 1-2, Days 5-6, and Days 9-10Population: All participants who received at least 1 dose of any study drug and had pharmacokinetic data available.
Outcome measures
| Measure |
Dasatinib, 100 mg as Tablets + Water
n=75 Participants
Treatment A: Participants received a single oral dose of dasatinib, 100 mg, administered as 2 50-mg tablets, plus 240 mL of noncarbonated, nonrefrigerated water. All doses were administered in the fasted state. A 3-day washout period followed the treatment period.
|
Dasatinib, 100 mg as Liquid + Water
n=77 Participants
Treatment B: Participants received a single oral dose of dasatinib, 100 mg, administered as 10 mL of reconstituted suspension of dasatinib powder for oral suspension (10 mg dasatinib/mL) with 230 mL of noncarbonated, nonrefrigerated water. All doses were administered in the fasted state. A 3-day washout period followed the treatment period.
|
Dasatinib, 100 mg as Tablets in Orange Juice + Water
n=77 Participants
Treatment C: Participants received a single oral dose of dasatinib, 100 mg, administered as 2 50-mg tablets dispersed in 30 mL of 100% orange juice, followed by 15 mL of orange juice as a rinsing solution plus 195 mL noncarbonated, nonrefrigerated water. All doses were administered in the fasted state.
|
|---|---|---|---|
|
Half-life of Dasatinib
|
4.96 Hours
Standard Deviation 1.31
|
4.82 Hours
Standard Deviation 1.17
|
4.91 Hours
Standard Deviation 1.25
|
SECONDARY outcome
Timeframe: Continually from enrollment through Day 9 and at study discharge on Day 10Population: All participants who received at least 1 dose of any study drug.
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.
Outcome measures
| Measure |
Dasatinib, 100 mg as Tablets + Water
n=78 Participants
Treatment A: Participants received a single oral dose of dasatinib, 100 mg, administered as 2 50-mg tablets, plus 240 mL of noncarbonated, nonrefrigerated water. All doses were administered in the fasted state. A 3-day washout period followed the treatment period.
|
Dasatinib, 100 mg as Liquid + Water
n=77 Participants
Treatment B: Participants received a single oral dose of dasatinib, 100 mg, administered as 10 mL of reconstituted suspension of dasatinib powder for oral suspension (10 mg dasatinib/mL) with 230 mL of noncarbonated, nonrefrigerated water. All doses were administered in the fasted state. A 3-day washout period followed the treatment period.
|
Dasatinib, 100 mg as Tablets in Orange Juice + Water
n=77 Participants
Treatment C: Participants received a single oral dose of dasatinib, 100 mg, administered as 2 50-mg tablets dispersed in 30 mL of 100% orange juice, followed by 15 mL of orange juice as a rinsing solution plus 195 mL noncarbonated, nonrefrigerated water. All doses were administered in the fasted state.
|
|---|---|---|---|
|
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)
At least 1 AE
|
42 Participants
|
44 Participants
|
35 Participants
|
|
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)
At least 1 treatment-related AE
|
39 Participants
|
43 Participants
|
34 Participants
|
|
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)
Discontinuation due to AEs
|
0 Participants
|
0 Participants
|
0 Participants
|
|
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)
At least 1 SAE
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day -1, Screening, and Days 1, 5, 9 and 10 (at study discharge)Population: All participants who received at least 1 dose of any study drug.
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.
Outcome measures
| Measure |
Dasatinib, 100 mg as Tablets + Water
n=78 Participants
Treatment A: Participants received a single oral dose of dasatinib, 100 mg, administered as 2 50-mg tablets, plus 240 mL of noncarbonated, nonrefrigerated water. All doses were administered in the fasted state. A 3-day washout period followed the treatment period.
|
Dasatinib, 100 mg as Liquid + Water
Treatment B: Participants received a single oral dose of dasatinib, 100 mg, administered as 10 mL of reconstituted suspension of dasatinib powder for oral suspension (10 mg dasatinib/mL) with 230 mL of noncarbonated, nonrefrigerated water. All doses were administered in the fasted state. A 3-day washout period followed the treatment period.
|
Dasatinib, 100 mg as Tablets in Orange Juice + Water
Treatment C: Participants received a single oral dose of dasatinib, 100 mg, administered as 2 50-mg tablets dispersed in 30 mL of 100% orange juice, followed by 15 mL of orange juice as a rinsing solution plus 195 mL noncarbonated, nonrefrigerated water. All doses were administered in the fasted state.
|
|---|---|---|---|
|
Number of Participants With Clinically Significant Changes in Vital Signs or Electrocardiogram (ECG) Findings
QRS and PR intervals
|
0 Participants
|
—
|
—
|
|
Number of Participants With Clinically Significant Changes in Vital Signs or Electrocardiogram (ECG) Findings
Respiratory rate
|
0 Participants
|
—
|
—
|
|
Number of Participants With Clinically Significant Changes in Vital Signs or Electrocardiogram (ECG) Findings
Temperature
|
0 Participants
|
—
|
—
|
|
Number of Participants With Clinically Significant Changes in Vital Signs or Electrocardiogram (ECG) Findings
Systolic blood pressure
|
0 Participants
|
—
|
—
|
|
Number of Participants With Clinically Significant Changes in Vital Signs or Electrocardiogram (ECG) Findings
Diastolic blood pressure
|
0 Participants
|
—
|
—
|
|
Number of Participants With Clinically Significant Changes in Vital Signs or Electrocardiogram (ECG) Findings
Heart rate
|
0 Participants
|
—
|
—
|
|
Number of Participants With Clinically Significant Changes in Vital Signs or Electrocardiogram (ECG) Findings
QT and QTc Intervals
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day -1, Screening, and Day 9 of current treatment regimenPopulation: All participants who received at least 1 dose of any study drug.
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.
Outcome measures
| Measure |
Dasatinib, 100 mg as Tablets + Water
n=78 Participants
Treatment A: Participants received a single oral dose of dasatinib, 100 mg, administered as 2 50-mg tablets, plus 240 mL of noncarbonated, nonrefrigerated water. All doses were administered in the fasted state. A 3-day washout period followed the treatment period.
|
Dasatinib, 100 mg as Liquid + Water
n=77 Participants
Treatment B: Participants received a single oral dose of dasatinib, 100 mg, administered as 10 mL of reconstituted suspension of dasatinib powder for oral suspension (10 mg dasatinib/mL) with 230 mL of noncarbonated, nonrefrigerated water. All doses were administered in the fasted state. A 3-day washout period followed the treatment period.
|
Dasatinib, 100 mg as Tablets in Orange Juice + Water
n=77 Participants
Treatment C: Participants received a single oral dose of dasatinib, 100 mg, administered as 2 50-mg tablets dispersed in 30 mL of 100% orange juice, followed by 15 mL of orange juice as a rinsing solution plus 195 mL noncarbonated, nonrefrigerated water. All doses were administered in the fasted state.
|
|---|---|---|---|
|
Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests
Blood in urine (2+)
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests
Elevated eosinophils
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests
Low erythrocytes
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests
Elevated bilirubin
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests
Elevated lactate dehydrogenase
|
0 Participants
|
1 Participants
|
0 Participants
|
Adverse Events
Dasatinib, 100 mg as Tablets + Water
Serious events: 0 serious events
Other events: 42 other events
Deaths: 0 deaths
Dasatinib, 100 mg as Liquid + Water
Serious events: 0 serious events
Other events: 44 other events
Deaths: 0 deaths
Dasatinib, 100 mg as Tablets in Orange Juice + Water
Serious events: 0 serious events
Other events: 35 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Dasatinib, 100 mg as Tablets + Water
n=78 participants at risk
Treatment A: Participants received a single oral dose of dasatinib, 100 mg, administered as 2 50-mg tablets, plus 240 mL of noncarbonated, nonrefrigerated water. All doses were administered in the fasted state. A 3-day washout period followed the treatment period.
|
Dasatinib, 100 mg as Liquid + Water
n=77 participants at risk
Treatment B: Participants received a single oral dose of dasatinib, 100 mg, administered as 10 mL of reconstituted suspension of dasatinib powder for oral suspension (10 mg dasatinib/mL) with 230 mL of noncarbonated, nonrefrigerated water. All doses were administered in the fasted state. A 3-day washout period followed the treatment period.
|
Dasatinib, 100 mg as Tablets in Orange Juice + Water
n=77 participants at risk
Treatment C: Participants received a single oral dose of dasatinib, 100 mg, administered as 2 50-mg tablets dispersed in 30 mL of 100% orange juice, followed by 15 mL of orange juice as a rinsing solution plus 195 mL noncarbonated, nonrefrigerated water. All doses were administered in the fasted state.
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
2.6%
2/78
|
1.3%
1/77
|
5.2%
4/77
|
|
Nervous system disorders
Headache
|
51.3%
40/78
|
55.8%
43/77
|
45.5%
35/77
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER