Trial Outcomes & Findings for A Study of the Effect of Quizartinib on the Pharmacokinetics of the P-gp Substrate Dabigatran Etexilate in Healthy Participants (NCT NCT04459585)
NCT ID: NCT04459585
Last Updated: 2021-07-09
Results Overview
Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis.
COMPLETED
EARLY_PHASE1
20 participants
Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)
2021-07-09
Participant Flow
A total of 20 participants who met all inclusion criteria and no exclusion criteria were enrolled from 28 Aug 2020 to 20 Oct 2020 at 1 clinic in the United States.
This study consisted of two treatment periods. Following a Screening Period of 21 days, eligible participants received only dabigatran etexilate (Reference Treatment) on Day 1 of Period 1 followed by quizartinib and dabigatran etexilate administration (Test Treatment) on Day 5 of Period 2.
Participant milestones
| Measure |
Dabigatran Etexilate/Dabigatran Etexilate + Quizartinib
Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1 and then received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on the morning of Day 5 of Period 2.
|
|---|---|
|
Period 1 (Day 1 to Day 5)
STARTED
|
20
|
|
Period 1 (Day 1 to Day 5)
COMPLETED
|
20
|
|
Period 1 (Day 1 to Day 5)
NOT COMPLETED
|
0
|
|
Period 2 (Day 5 to Day 12)
STARTED
|
20
|
|
Period 2 (Day 5 to Day 12)
COMPLETED
|
20
|
|
Period 2 (Day 5 to Day 12)
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of the Effect of Quizartinib on the Pharmacokinetics of the P-gp Substrate Dabigatran Etexilate in Healthy Participants
Baseline characteristics by cohort
| Measure |
Dabigatran Etexilate/Dabigatran Etexilate + Quizartinib
n=20 Participants
Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1 and then received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on the morning of Day 5 of Period 2.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
20 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
|
Age, Continuous
|
39.0 years
STANDARD_DEVIATION 10.37 • n=99 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
12 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.
Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis.
Outcome measures
| Measure |
Period 1: Dabigatran Etexilate
n=20 Participants
Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1.
|
Period 2: Dabigatran Etexilate + Quizartinib
n=20 Participants
Participants who received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on Day 5 of Period 2.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib
Total Dabigatran
|
192 ng/mL
Standard Deviation 94.5
|
239 ng/mL
Standard Deviation 141
|
|
Maximum Plasma Concentration (Cmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib
Free Dabigatran
|
159 ng/mL
Standard Deviation 82.2
|
201 ng/mL
Standard Deviation 127
|
PRIMARY outcome
Timeframe: Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.
Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method and was calculated using non-compartmental analysis.
Outcome measures
| Measure |
Period 1: Dabigatran Etexilate
n=20 Participants
Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1.
|
Period 2: Dabigatran Etexilate + Quizartinib
n=20 Participants
Participants who received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on Day 5 of Period 2.
|
|---|---|---|
|
Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib
Total Dabigatran
|
1720 ng*h/mL
Standard Deviation 870
|
2100 ng*h/mL
Standard Deviation 1280
|
|
Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib
Free Dabigatran
|
1390 ng*h/mL
Standard Deviation 736
|
1710 ng*h/mL
Standard Deviation 1100
|
PRIMARY outcome
Timeframe: Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)Population: The pharmacokinetic parameter of Area Under the Plasma Concentration-Time Curve up to Infinity was assessed using the Pharmacokinetic Analysis Set except for 1 participant that did not meet the protocol inclusion criteria for this analysis.
Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity and was calculated using non-compartmental analysis.
Outcome measures
| Measure |
Period 1: Dabigatran Etexilate
n=20 Participants
Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1.
|
Period 2: Dabigatran Etexilate + Quizartinib
n=20 Participants
Participants who received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on Day 5 of Period 2.
|
|---|---|---|
|
Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib
Total Dabigatran
|
1740 ng*h/mL
Standard Deviation 902
|
2140 ng*h/mL
Standard Deviation 1280
|
|
Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib
Free Dabigatran
|
1420 ng*h/mL
Standard Deviation 760
|
1730 ng*h/mL
Standard Deviation 1100
|
SECONDARY outcome
Timeframe: Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.
Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was calculated using non-compartmental analysis.
Outcome measures
| Measure |
Period 1: Dabigatran Etexilate
n=20 Participants
Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1.
|
Period 2: Dabigatran Etexilate + Quizartinib
n=20 Participants
Participants who received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on Day 5 of Period 2.
|
|---|---|---|
|
Time of Maximum Plasma Concentration (Tmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib
Total Dabigatran
|
2.0 hours
Interval 1.5 to 3.1
|
2.0 hours
Interval 1.5 to 4.0
|
|
Time of Maximum Plasma Concentration (Tmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib
Free Dabigatran
|
2.0 hours
Interval 1.5 to 4.0
|
2.0 hours
Interval 1.5 to 4.0
|
SECONDARY outcome
Timeframe: Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)Population: The pharmacokinetic parameter of Terminal Elimination Half-Life was assessed using the Pharmacokinetic Analysis Set except for 1 participant that did not meet the protocol inclusion criteria for this analysis.
Terminal Elimination Half-Life (T1/2) is defined as terminal elimination half-life and was calculated using non-compartmental analysis.
Outcome measures
| Measure |
Period 1: Dabigatran Etexilate
n=20 Participants
Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1.
|
Period 2: Dabigatran Etexilate + Quizartinib
n=20 Participants
Participants who received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on Day 5 of Period 2.
|
|---|---|---|
|
Terminal Elimination Half-Life (T1/2) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib
Total Dabigatran
|
15.4 hours
Standard Deviation 4.4
|
18.1 hours
Standard Deviation 17.0
|
|
Terminal Elimination Half-Life (T1/2) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib
Free Dabigatran
|
14.2 hours
Standard Deviation 4.2
|
14.1 hours
Standard Deviation 6.6
|
SECONDARY outcome
Timeframe: Period 2 Day 5 (Pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.
Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis. Cmax was assessed for Quizartinib and Metabolite AC886.
Outcome measures
| Measure |
Period 1: Dabigatran Etexilate
n=20 Participants
Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1.
|
Period 2: Dabigatran Etexilate + Quizartinib
Participants who received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on Day 5 of Period 2.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants
AC886
|
25.7 ng/mL
Standard Deviation 8.71
|
—
|
|
Maximum Plasma Concentration (Cmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants
Quizartinib
|
250 ng/mL
Standard Deviation 50.8
|
—
|
SECONDARY outcome
Timeframe: Period 2 Day 5 (Pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.
Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was calculated using non-compartmental analysis. Tmax was assessed for Quizartinib and Metabolite AC886.
Outcome measures
| Measure |
Period 1: Dabigatran Etexilate
n=20 Participants
Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1.
|
Period 2: Dabigatran Etexilate + Quizartinib
Participants who received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on Day 5 of Period 2.
|
|---|---|---|
|
Time of Maximum Plasma Concentration (Tmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants
Quizartinib
|
3.0 hours
Interval 2.5 to 6.0
|
—
|
|
Time of Maximum Plasma Concentration (Tmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants
AC886
|
8.0 hours
Interval 3.5 to 26.1
|
—
|
SECONDARY outcome
Timeframe: Period 2 Day 5 (Pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.
Area Under the Plasma Concentration-Time Curve From Time 0 to 74 Hours (AUClast,74) is defined as area under the plasma concentration-time curve to the last quantifiable concentration post dose at 74 hours and was calculated using non-compartmental analysis. AUClast,74 was assessed for Quizartinib and Metabolite AC886.
Outcome measures
| Measure |
Period 1: Dabigatran Etexilate
n=20 Participants
Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1.
|
Period 2: Dabigatran Etexilate + Quizartinib
Participants who received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on Day 5 of Period 2.
|
|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time 0 to 74 Hours (AUClast,74) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants
Quizartinib
|
9390 ng*h/mL
Standard Deviation 1660
|
—
|
|
Area Under the Plasma Concentration-Time Curve From Time 0 to 74 Hours (AUClast,74) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants
AC886
|
1350 ng*h/mL
Standard Deviation 495
|
—
|
SECONDARY outcome
Timeframe: Up to 2 monthsPopulation: TEAEs were assessed using the Safety Analysis Set.
A Treatment-Emergent Adverse Events (TEAE) is defined as any event not present prior to the initiation of the drug treatment of the drug treatment or any event already present that worsens in either intensity or frequency following exposure to the drug treatment. Number of any TEAE that is related and unrelated to study medication is presented.
Outcome measures
| Measure |
Period 1: Dabigatran Etexilate
n=20 Participants
Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1.
|
Period 2: Dabigatran Etexilate + Quizartinib
n=20 Participants
Participants who received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on Day 5 of Period 2.
|
|---|---|---|
|
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAE) Relatedness to Study Medication Following Single Dose of Dabigatran Without and With Quizartinib in Participants
Related
|
0 Participants
|
2 Participants
|
|
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAE) Relatedness to Study Medication Following Single Dose of Dabigatran Without and With Quizartinib in Participants
Unrelated
|
0 Participants
|
1 Participants
|
Adverse Events
Period 1: Dabigatran Etexilate
Period 2: Dabigatran Etexilate + Quizartinib
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Period 1: Dabigatran Etexilate
n=20 participants at risk
Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1.
|
Period 2: Dabigatran Etexilate + Quizartinib
n=20 participants at risk
Participants who received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on Day 5 of Period 2.
|
|---|---|---|
|
Nervous system disorders
Dizziness
|
0.00%
0/20 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months.
Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
|
5.0%
1/20 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months.
Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
|
|
Nervous system disorders
Headache
|
0.00%
0/20 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months.
Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
|
5.0%
1/20 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months.
Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/20 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months.
Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
|
5.0%
1/20 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months.
Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
|
Additional Information
Contact for Clinical Trial Information
Daiichi Sankyo, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place