Study of Quizartinib in Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Sponsor
Daiichi Sankyo Co., Ltd. (Industry)
Overall Status
Completed
CT.gov ID
NCT02834390
Collaborator
(none)
7
1
2
14.2
0.5
Study Details
Study Description
Brief Summary
This is a phase 1b, dose escalation, study of quizartinib to evaluate the safety profile, the pharmacokinetics, and the recommended dose of quizartinib for subsequent clinical studies of the combination of quizartinib and induction and consolidation chemotherapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
7 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1b, Open-label, Dose Escalation Study of Quizartinib in Combination With Induction and Consolidation Chemotherapy in Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Actual Study Start Date
:
Aug 12, 2016
Actual Primary Completion Date
:
Oct 19, 2017
Actual Study Completion Date
:
Oct 19, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Quizartinib 20 mg/day Participants who received 20 mg quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. |
Drug: Quizartinib
[Induction period, Cycle 1] Once-daily repeated oral administration Day 8 to Day 21.
[Induction period, Cycle 2] Once-daily repeated oral administration Day 6 to Day 19.
[Consolidation period] Once-daily repeated oral administration Day 6 to Day 19.
Drug: Cytarabine
[Induction period, Cycle 1] Once-daily intravenous injection of 100 mg/m^2 cytarabine on Day 1 to 7.
[Induction period, Cycle 2] Once-daily intravenous injection of 100 mg/m^2 cytarabine on Day 1 to 5.
[Consolidation period] Twice-daily intravenous injection of 3.0 g/m^2 cytarabine at 12-hour intervals on Days 1, 3, and 5.
Drug: Idarubicin
Either Idarubicin or Daunorubicin will be used [Induction period, Cycle 1] Once-daily intravenous injection of 12 mg/m^2 idarubicin on Day 1 to 3.
[Induction period, Cycle 2] Once-daily intravenous injection of 12 mg/m^2 idarubicin on Day 1 and 2.
Drug: Daunorubicin
Either Idarubicin or Daunorubicin will be used [Induction period, Cycle 1] Once-daily intravenous injection of 60mg/m^2 daunorubicin on Day 1 to 3.
[Induction period, Cycle 2] Once-daily intravenous injection of 60mg/m^2 daunorubicin on Day 1 and 2.
|
| Experimental: Quizartinib 40 mg/day Participants who received 40 mg quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. |
Drug: Quizartinib
[Induction period, Cycle 1] Once-daily repeated oral administration Day 8 to Day 21.
[Induction period, Cycle 2] Once-daily repeated oral administration Day 6 to Day 19.
[Consolidation period] Once-daily repeated oral administration Day 6 to Day 19.
Drug: Cytarabine
[Induction period, Cycle 1] Once-daily intravenous injection of 100 mg/m^2 cytarabine on Day 1 to 7.
[Induction period, Cycle 2] Once-daily intravenous injection of 100 mg/m^2 cytarabine on Day 1 to 5.
[Consolidation period] Twice-daily intravenous injection of 3.0 g/m^2 cytarabine at 12-hour intervals on Days 1, 3, and 5.
Drug: Idarubicin
Either Idarubicin or Daunorubicin will be used [Induction period, Cycle 1] Once-daily intravenous injection of 12 mg/m^2 idarubicin on Day 1 to 3.
[Induction period, Cycle 2] Once-daily intravenous injection of 12 mg/m^2 idarubicin on Day 1 and 2.
Drug: Daunorubicin
Either Idarubicin or Daunorubicin will be used [Induction period, Cycle 1] Once-daily intravenous injection of 60mg/m^2 daunorubicin on Day 1 to 3.
[Induction period, Cycle 2] Once-daily intravenous injection of 60mg/m^2 daunorubicin on Day 1 and 2.
|
Outcome Measures
Primary Outcome Measures
- Summary of Best Responses After a Daily Dose of 20 mg or 40 mg in Combination With Standard Chemotherapy to Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) [Day 0 to Day 21 of last completed cycle (each cycle 28 days), up to approximately 1 year]
Best response was defined as the best measured complete remission (CR), CR with incomplete hematological recovery (CRi), CR with incomplete platelet recovery (CRp), Partial remission (PR), or No response (NR) in the overall response assessments at all time points after the first dose.
- Summary of Best Response Rates After the First Oral Dose of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia [Day 0 to Day 21 of last completed cycle (each cycle 28 days), up to approximately 1 year]
Best response was defined as the best measured complete remission (CR), CR with incomplete hematological recovery (CRi), CR with incomplete platelet recovery (CRp), Partial remission (PR), or No response (NR) in the overall response assessments at all time points after the first dose.
- Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of Geometric Means of Quizartinib and Active Metabolite (AC886) After Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia [Induction phase Cycle 1, Day 8 to Cycle 1, Day 21 (each cycle 28 days)]
The maximum serum plasma concentration (Cmax) is reported at Induction phase Cycle 1, Day 9 and the maximum serum plasma concentration at steady state (Cmax,ss) is reported at Induction phase Cycle 1, Day 21 for quizartinib, active metabolite AC886, and quizartinib and AC886.
- Pharmacokinetic Parameter Area Under the Concentration-Time Curve During Dosing Interval of Quizartinib and Metabolite (AC886) After Daily Dose of 20 mg or 40 mg With Chemotherapy to Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia [Induction phase Cycle 1, Day 8 to Cycle 1, Day 21 (each cycle 28 days)]
The area under the plasma concentration-time curve during dosing interval (AUCtau) of geometric means is reported at Induction phase Cycle 1, Day 9 and the area under the plasma concentration-time curve during dosing interval at steady state (AUCtauss) of geometric means are reported at Induction phase Cycle 1, Day 21 for quizartinib, active metabolite AC886, and quizartinib and AC886.
- Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Quizartinib and the Active Metabolite (AC886) After a Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) [Induction phase Cycle 1, Day 8 to Cycle 1, Day 21 (each cycle 28 days)]
The time of maximum plasma concentration (Tmax) of geometric means is reported at Induction phase Cycle 1, Day 9 and the time of maximum plasma concentration at steady state (Tmax,ss) of geometric means is reported at Induction phase Cycle 1, Day 21 for quizartinib, active metabolite AC886, and quizartinib and AC886.
- Pharmacokinetic Parameter Metabolite to Parent Ratio (MR) of Active Metabolite (AC886) After a Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) [Induction phase Cycle 1, Day 8 (each cycle 28 days)]
The metabolite to parent ratio of geometric means for Cmax and AUCtau is reported at Induction phase Cycle 1, Day 9 for active metabolite AC886 is reported.
- Pharmacokinetic Parameter Trough Plasma Concentration (Ctrough) of Quizartinib and Active Metabolite (AC886) After a Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) [Induction phase Cycle 1, Day 21 (each cycle 28 days)]
The trough plasma concentration (Ctrough) of geometric means is reported at Induction phase Cycle 1, Day 21 for serum quizartinib, active metabolite AC886, and quizartinib and AC886.
- Pharmacokinetic Parameter Accumulation Ratio (AR) of Quizartinib and Active Metabolite (AC886) After a Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) [Induction phase Cycle 1, Day 21 (each cycle 28 days)]
The accumulation ratio of geometric means for Cmax and AUCtau is reported at Induction phase Cycle 1, Day 21 for serum quizartinib, active metabolite AC886, and quizartinib and AC886.
- Number of Participants Treatment-Emergent Adverse Events Reported During Induction Phase After a Daily Dose of 20 mg or 40 mg in Combination With Standard Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) [Induction phase Cycle 1, Day 1 up to 35 days after last dose in Cycle 2 (each cycle 28 days), up to approximately 1 year]
A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that emerges (or worsens) from the first dose of study drug and coadministered drugs to the follow-up visit, 35 days after the last dose of study drug and coadministered drugs, or the start date of new AML post-treatment, whichever was earlier.
- Number of Participants Treatment-Emergent Adverse Events Reported During Consolidation Phase After a Daily Dose of 20 mg or 40 mg in Combination With Standard Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) [Consolidation phase Cycle 1, Day 1 up to 35 days after last dose (each cycle 28 days), up to approximately 1 year]
A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that emerges (or worsens) from the first dose of study drug and coadministered drugs to the follow-up visit, 35 days after the last dose of study drug and coadministered drugs, or the start date of new AML post-treatment, whichever was earlier.
Eligibility Criteria
Criteria
Ages Eligible for Study:
20 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
No prior treatment for AML (including quizartinib)
-
ECOG (Eastern Cooperative Oncology Group) Performance Status of 0 to 2
Exclusion Criteria:
-
Diagnosis of acute promyelocytic leukemia
-
Active acute or chronic systemic fungal, bacterial, or viral infection not well controlled by antifungal, antibacterial or antiviral therapy.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tokyo | Japan |
Sponsors and Collaborators
- Daiichi Sankyo Co., Ltd.
Investigators
- Study Director: Global Clinical Leader, Daiichi Sankyo, Inc.
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier:
NCT02834390
Other Study ID Numbers:
- AC220-A-J102
First Posted:
Jul 15, 2016
Last Update Posted:
Aug 19, 2021
Last Verified:
Jul 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
Yes
Keywords provided by Daiichi Sankyo Co., Ltd.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | A total of 7 participants who met all inclusion and no exclusion criteria were enrolled and received treatment in the study. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Quizartinib 20 mg/Day | Quizartinib 40 mg/Day |
|---|---|---|
| Arm/Group Description | Participants who received 20 mg quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. | Participants who received 40 mg/day quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. |
| Period Title: Induction Phase | ||
| STARTED | 4 | 3 |
| COMPLETED | 2 | 1 |
| NOT COMPLETED | 2 | 2 |
| Period Title: Induction Phase | ||
| STARTED | 2 | 1 |
| COMPLETED | 1 | 0 |
| NOT COMPLETED | 1 | 1 |
Baseline Characteristics
| Arm/Group Title | Quizartinib 20 mg/Day | Quizartinib 40 mg/Day | Total |
|---|---|---|---|
| Arm/Group Description | Participants who received 20 mg quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. | Participants who received 40 mg/day quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. | Total of all reporting groups |
| Overall Participants | 4 | 3 | 7 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
2
50%
|
2
66.7%
|
4
57.1%
|
| >=65 years |
2
50%
|
1
33.3%
|
3
42.9%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
57.5
(10.5)
|
53.7
(17.1)
|
55.9
(12.5)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
2
50%
|
2
66.7%
|
4
57.1%
|
| Male |
2
50%
|
1
33.3%
|
3
42.9%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
4
100%
|
3
100%
|
7
100%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| White |
0
0%
|
0
0%
|
0
0%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| Japan |
4
100%
|
3
100%
|
7
100%
|
Outcome Measures
| Title | Summary of Best Responses After a Daily Dose of 20 mg or 40 mg in Combination With Standard Chemotherapy to Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) |
|---|---|
| Description | Best response was defined as the best measured complete remission (CR), CR with incomplete hematological recovery (CRi), CR with incomplete platelet recovery (CRp), Partial remission (PR), or No response (NR) in the overall response assessments at all time points after the first dose. |
| Time Frame | Day 0 to Day 21 of last completed cycle (each cycle 28 days), up to approximately 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| Best response was assessed in the Efficacy Analysis Set. |
| Arm/Group Title | Quizartinib 20 mg/Day | Quizartinib 40 mg/Day |
|---|---|---|
| Arm/Group Description | Participants who received 20 mg quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. | Participants who received 40 mg/day quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. |
| Measure Participants | 4 | 3 |
| Complete remission (CR) |
0
0%
|
0
0%
|
| CR with incomplete platelet recovery (CRp) |
0
0%
|
0
0%
|
| CR with incomplete hematological recovery (CRi) |
3
75%
|
2
66.7%
|
| Partial remission (PR) |
1
25%
|
0
0%
|
| No response (NR) |
0
0%
|
1
33.3%
|
| Title | Summary of Best Response Rates After the First Oral Dose of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia |
|---|---|
| Description | Best response was defined as the best measured complete remission (CR), CR with incomplete hematological recovery (CRi), CR with incomplete platelet recovery (CRp), Partial remission (PR), or No response (NR) in the overall response assessments at all time points after the first dose. |
| Time Frame | Day 0 to Day 21 of last completed cycle (each cycle 28 days), up to approximately 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| Best response was assessed in the Efficacy Analysis Set. |
| Arm/Group Title | Quizartinib 20 mg/Day | Quizartinib 40 mg/Day |
|---|---|---|
| Arm/Group Description | Participants who received 20 mg quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. | Participants who received 40 mg/day quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. |
| Measure Participants | 4 | 3 |
| Composite CR rate (CRc rate: CR+CRp+CRi) |
75.0
1875%
|
66.7
2223.3%
|
| Response rate (CRc+PR) |
100
2500%
|
66.7
2223.3%
|
| Title | Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of Geometric Means of Quizartinib and Active Metabolite (AC886) After Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia |
|---|---|
| Description | The maximum serum plasma concentration (Cmax) is reported at Induction phase Cycle 1, Day 9 and the maximum serum plasma concentration at steady state (Cmax,ss) is reported at Induction phase Cycle 1, Day 21 for quizartinib, active metabolite AC886, and quizartinib and AC886. |
| Time Frame | Induction phase Cycle 1, Day 8 to Cycle 1, Day 21 (each cycle 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. |
| Arm/Group Title | Quizartinib 20 mg/Day | Quizartinib 40 mg/Day |
|---|---|---|
| Arm/Group Description | Participants who received 20 mg quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. | Participants who received 40 mg/day quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. |
| Measure Participants | 4 | 3 |
| Cycle 1, Day 8: Quizartinib, Cmax |
42.4
(25.7)
|
91.3
(28.5)
|
| Cycle 1, Day 8: AC886, Cmax |
36.5
(25.4)
|
103
(37.0)
|
| Cycle 1, Day 8: Quizartinib + AC886, Cmax |
77.4
(10.3)
|
180
(16.0)
|
| Cycle 1, Day 21: Quizartinib, Cmax, ss |
64.2
(64.0)
|
212
(47.4)
|
| Cycle 1, Day 21: AC886, Cmax, ss |
96.7
(23.7)
|
256
(45.0)
|
| Cycle 1, Day 21: Quizartinib + AC886, Cmax |
162
(35.3)
|
480
(2.4)
|
| Title | Pharmacokinetic Parameter Area Under the Concentration-Time Curve During Dosing Interval of Quizartinib and Metabolite (AC886) After Daily Dose of 20 mg or 40 mg With Chemotherapy to Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia |
|---|---|
| Description | The area under the plasma concentration-time curve during dosing interval (AUCtau) of geometric means is reported at Induction phase Cycle 1, Day 9 and the area under the plasma concentration-time curve during dosing interval at steady state (AUCtauss) of geometric means are reported at Induction phase Cycle 1, Day 21 for quizartinib, active metabolite AC886, and quizartinib and AC886. |
| Time Frame | Induction phase Cycle 1, Day 8 to Cycle 1, Day 21 (each cycle 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. |
| Arm/Group Title | Quizartinib 20 mg/Day | Quizartinib 40 mg/Day |
|---|---|---|
| Arm/Group Description | Participants who received 20 mg quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. | Participants who received 40 mg/day quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. |
| Measure Participants | 4 | 3 |
| Cycle 1, Day 8: Quizartinib, AUCtau |
418
(50.4)
|
921
(31.3)
|
| Cycle 1, Day 8: AC886, AUCtau |
555
(28.8)
|
1640
(24.4)
|
| Cycle 1, Day 8: Quizartinib + AC886, AUCtau |
1010
(26.9)
|
2640
(8.0)
|
| Cycle 1, Day 21: Quizartinib, AUCtau,ss |
991
(87.7)
|
2940
(76.6)
|
| Cycle 1, Day 21: AC886, AUCtau, ss |
1940
(25.4)
|
5310
(40.6)
|
| Cycle 1, Day 21: Quizartinib + AC886, AUCtau |
3020
(42.3)
|
8850
(0.3)
|
| Title | Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Quizartinib and the Active Metabolite (AC886) After a Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) |
|---|---|
| Description | The time of maximum plasma concentration (Tmax) of geometric means is reported at Induction phase Cycle 1, Day 9 and the time of maximum plasma concentration at steady state (Tmax,ss) of geometric means is reported at Induction phase Cycle 1, Day 21 for quizartinib, active metabolite AC886, and quizartinib and AC886. |
| Time Frame | Induction phase Cycle 1, Day 8 to Cycle 1, Day 21 (each cycle 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. |
| Arm/Group Title | Quizartinib 20 mg/Day | Quizartinib 40 mg/Day |
|---|---|---|
| Arm/Group Description | Participants who received 20 mg quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. | Participants who received 40 mg/day quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. |
| Measure Participants | 4 | 3 |
| Cycle 1, Day 8: Quizartinib, Tmax |
3.03
|
2.17
|
| Cycle 1, Day 8: AC886, Tmax |
5.01
|
6.08
|
| Cycle 1, Day 8: Quizartinib + AC886, Tmax |
4.01
|
4.17
|
| Cycle 1, Day 21: Quizartinib, Tmax,ss |
4.03
|
4.08
|
| Cycle 1, Day 21: AC886, Tmax,ss |
5.02
|
6.09
|
| Cycle 1, Day 21: Quizartinib + AC886, Tmax |
4.03
|
4.08
|
| Title | Pharmacokinetic Parameter Metabolite to Parent Ratio (MR) of Active Metabolite (AC886) After a Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) |
|---|---|
| Description | The metabolite to parent ratio of geometric means for Cmax and AUCtau is reported at Induction phase Cycle 1, Day 9 for active metabolite AC886 is reported. |
| Time Frame | Induction phase Cycle 1, Day 8 (each cycle 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. |
| Arm/Group Title | Quizartinib 20 mg/Day | Quizartinib 40 mg/Day |
|---|---|---|
| Arm/Group Description | Participants who received 20 mg quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. | Participants who received 40 mg/day quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. |
| Measure Participants | 4 | 3 |
| Cycle 1, Day 8: MR (Cmax) |
0.861
(43.8)
|
1.13
(45.6)
|
| Cycle 1, Day 8: MR (AUCtau) |
1.33
(64.1)
|
1.78
(56.4)
|
| Title | Pharmacokinetic Parameter Trough Plasma Concentration (Ctrough) of Quizartinib and Active Metabolite (AC886) After a Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) |
|---|---|
| Description | The trough plasma concentration (Ctrough) of geometric means is reported at Induction phase Cycle 1, Day 21 for serum quizartinib, active metabolite AC886, and quizartinib and AC886. |
| Time Frame | Induction phase Cycle 1, Day 21 (each cycle 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. |
| Arm/Group Title | Quizartinib 20 mg/Day | Quizartinib 40 mg/Day |
|---|---|---|
| Arm/Group Description | Participants who received 20 mg quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. | Participants who received 40 mg/day quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. |
| Measure Participants | 4 | 2 |
| Cycle 1, Day 21: Quizartinib |
22.7
(173.4)
|
77.1
(117.6)
|
| Cycle 1, Day 21: AC886 |
68.6
(49.3)
|
195
(46.1)
|
| Cycle 1, Day 21: Quizartinib + AC886 |
94.6
(68.5)
|
299
(3.3)
|
| Title | Pharmacokinetic Parameter Accumulation Ratio (AR) of Quizartinib and Active Metabolite (AC886) After a Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) |
|---|---|
| Description | The accumulation ratio of geometric means for Cmax and AUCtau is reported at Induction phase Cycle 1, Day 21 for serum quizartinib, active metabolite AC886, and quizartinib and AC886. |
| Time Frame | Induction phase Cycle 1, Day 21 (each cycle 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. |
| Arm/Group Title | Quizartinib 20 mg/Day | Quizartinib 40 mg/Day |
|---|---|---|
| Arm/Group Description | Participants who received 20 mg quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. | Participants who received 40 mg/day quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. |
| Measure Participants | 4 | 2 |
| Cycle 1, Day 21: Quizartinib AR (Cmax) |
1.52
(72.1)
|
1.98
(58.5)
|
| Cycle 1, Day 21: AC886 AR (Cmax) |
2.65
(46.9)
|
2.55
(7.2)
|
| Cycle 1, Day 21: Quizartinib + AC886 AR (Cmax) |
2.09
(41.6)
|
2.53
(16.2)
|
| Cycle 1, Day 21: Quizartinib AR (AUCtau) |
2.37
(88.5)
|
2.84
(36.2)
|
| Cycle 1, Day 21: AC886 AR (AUCtau) |
3.50
(56.2)
|
3.31
(5.4)
|
| Cycle 1, Day 21: Quizartinib + AC886 AR (AUCtau) |
2.99
(59.5)
|
3.24
(6.8)
|
| Title | Number of Participants Treatment-Emergent Adverse Events Reported During Induction Phase After a Daily Dose of 20 mg or 40 mg in Combination With Standard Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) |
|---|---|
| Description | A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that emerges (or worsens) from the first dose of study drug and coadministered drugs to the follow-up visit, 35 days after the last dose of study drug and coadministered drugs, or the start date of new AML post-treatment, whichever was earlier. |
| Time Frame | Induction phase Cycle 1, Day 1 up to 35 days after last dose in Cycle 2 (each cycle 28 days), up to approximately 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| Adverse events were assessed in the Safety Analysis Set. |
| Arm/Group Title | Quizartinib 20 mg/Day | Quizartinib 40 mg/Day |
|---|---|---|
| Arm/Group Description | Participants who received 20 mg quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. | Participants who received 40 mg/day quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. |
| Measure Participants | 4 | 3 |
| Participants with TEAEs |
4
100%
|
3
100%
|
| Infections and Infestations |
1
25%
|
3
100%
|
| Pneumonia |
1
25%
|
1
33.3%
|
| Skin infection |
0
0%
|
1
33.3%
|
| Staphylococcal bacteraemia |
0
0%
|
1
33.3%
|
| Blood and Lymphatic System Disorders |
4
100%
|
3
100%
|
| Febrile neutropenia |
4
100%
|
3
100%
|
| Anaemia |
2
50%
|
1
33.3%
|
| Leukopenia |
1
25%
|
0
0%
|
| Neutropenia |
1
25%
|
0
0%
|
| Thrombocytopenia |
1
25%
|
0
0%
|
| Immune Disorders |
0
0%
|
1
33.3%
|
| Hypersensitivity |
0
0%
|
1
33.3%
|
| Metabolism and Nutrition Disorders |
3
75%
|
2
66.7%
|
| Decreased appetite |
3
75%
|
1
33.3%
|
| Hypoalbuminaemia |
1
25%
|
1
33.3%
|
| Hypokalaemia |
2
50%
|
0
0%
|
| Hypomagnesaemia |
1
25%
|
0
0%
|
| Hyponatraemia |
1
25%
|
0
0%
|
| Hypophosphataemia |
1
25%
|
0
0%
|
| Hypouricaemia |
0
0%
|
1
33.3%
|
| Tumour lysis syndrome |
1
25%
|
0
0%
|
| Nervous System Disorders |
2
50%
|
1
33.3%
|
| Dysgeusia |
2
50%
|
1
33.3%
|
| Dizziness |
1
25%
|
0
0%
|
| Eye Disorders |
1
25%
|
0
0%
|
| Photophobia |
1
25%
|
0
0%
|
| Cardiac Disorders |
0
0%
|
1
33.3%
|
| Palpitations |
0
0%
|
1
33.3%
|
| Vascular Disorders |
0
0%
|
1
33.3%
|
| Hypotension |
0
0%
|
1
33.3%
|
| Respiratory, Thoracic, and Mediastinal Disorders |
0
0%
|
1
33.3%
|
| Epistaxis |
0
0%
|
1
33.3%
|
| Oropharyngeal pain |
0
0%
|
1
33.3%
|
| Respiratory disorder |
0
0%
|
1
33.3%
|
| Gastrointestinal Disorders |
3
75%
|
3
100%
|
| Abdominal pain upper |
3
75%
|
1
33.3%
|
| Nausea |
2
50%
|
2
66.7%
|
| Constipation |
1
25%
|
2
66.7%
|
| Diarrhoea |
1
25%
|
2
66.7%
|
| Stomatitis |
2
50%
|
1
33.3%
|
| Cheilitis |
1
25%
|
1
33.3%
|
| Vomiting |
1
25%
|
1
33.3%
|
| Melaena |
0
0%
|
1
33.3%
|
| Hepatobiliary Disorders |
0
0%
|
1
33.3%
|
| Hepatic function abnormal |
0
0%
|
1
33.3%
|
| Skin and Subcutaneous Tissue Disorders |
4
100%
|
3
100%
|
| Alopecia |
3
75%
|
2
66.7%
|
| Rash |
1
25%
|
2
66.7%
|
| Rash maculo-papular |
1
25%
|
1
33.3%
|
| Dermatitis bullous |
0
0%
|
1
33.3%
|
| Dry skin |
0
0%
|
1
33.3%
|
| Musculoskeletal and Connective Tissue Disorders |
1
25%
|
3
100%
|
| Arthralgia |
0
0%
|
2
66.7%
|
| Musculoskeletal pain |
0
0%
|
1
33.3%
|
| Myalgia |
1
25%
|
0
0%
|
| Pain in extremity |
0
0%
|
1
33.3%
|
| Renal and Urinary Disorders |
1
25%
|
0
0%
|
| Haematuria |
1
25%
|
0
0%
|
| Proteinuria |
1
25%
|
0
0%
|
| Urinary tract pain |
1
25%
|
0
0%
|
| Reproductive System and Breast Disorders |
0
0%
|
1
33.3%
|
| Menorrhagia |
0
0%
|
1
33.3%
|
| General Disorders & Administration Site Conditions |
0
0%
|
1
33.3%
|
| Oedema peripheral |
0
0%
|
1
33.3%
|
| Pyrexia |
0
0%
|
1
33.3%
|
| Investigations |
4
100%
|
3
100%
|
| Gamma-glutamyltransferase increased |
3
75%
|
1
33.3%
|
| Alanine aminotransferase increased |
2
50%
|
1
33.3%
|
| Blood alkaline phosphatase increased |
1
25%
|
1
33.3%
|
| Electrocardiogram QT prolonged |
0
0%
|
2
66.7%
|
| Platelet count decreased |
1
25%
|
1
33.3%
|
| Weight decreased |
1
25%
|
1
33.3%
|
| White blood cell count decreased |
1
25%
|
1
33.3%
|
| Aspartate aminotransferase |
1
25%
|
0
0%
|
| Aspartate aminotransferase increased |
0
0%
|
1
33.3%
|
| Blood bilirubin increased |
1
25%
|
0
0%
|
| Blood lactate dehydrogenase increased |
0
0%
|
1
33.3%
|
| Blood pressure decreased |
0
0%
|
1
33.3%
|
| Lipase increased |
0
0%
|
1
33.3%
|
| Title | Number of Participants Treatment-Emergent Adverse Events Reported During Consolidation Phase After a Daily Dose of 20 mg or 40 mg in Combination With Standard Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) |
|---|---|
| Description | A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that emerges (or worsens) from the first dose of study drug and coadministered drugs to the follow-up visit, 35 days after the last dose of study drug and coadministered drugs, or the start date of new AML post-treatment, whichever was earlier. |
| Time Frame | Consolidation phase Cycle 1, Day 1 up to 35 days after last dose (each cycle 28 days), up to approximately 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| Adverse events were assessed in the Safety Analysis Set. |
| Arm/Group Title | Quizartinib 20 mg/Day | Quizartinib 40 mg/Day |
|---|---|---|
| Arm/Group Description | Participants who received 20 mg quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. | Participants who received 40 mg/day quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. |
| Measure Participants | 2 | 1 |
| Participants with TEAEs |
2
50%
|
1
33.3%
|
| Infections and Infestations |
1
25%
|
1
33.3%
|
| Lung infection |
0
0%
|
1
33.3%
|
| Skin infection |
1
25%
|
0
0%
|
| Upper respiratory tract infection |
1
25%
|
0
0%
|
| Blood and Lymphatic System Disorders |
2
50%
|
1
33.3%
|
| Febrile neutropenia |
2
50%
|
1
33.3%
|
| Nervous System Disorders |
1
25%
|
0
0%
|
| Dysgeusia |
1
25%
|
0
0%
|
| Gastrointestinal Disorders |
2
50%
|
0
0%
|
| Diarrhoea |
2
50%
|
0
0%
|
| Nausea |
1
25%
|
0
0%
|
| Stomatitis |
1
25%
|
0
0%
|
| Skin and Subcutaneous Tissue Disorders |
1
25%
|
1
33.3%
|
| Rash |
1
25%
|
0
0%
|
| Rash maculo-papular |
0
0%
|
1
33.3%
|
| General Disorders & Administration Site Conditions |
1
25%
|
0
0%
|
| Oedema peripheral |
1
25%
|
0
0%
|
| Investigations |
2
50%
|
1
33.3%
|
| Platelet count decreased |
1
25%
|
1
33.3%
|
| White blood cell count decreased |
1
25%
|
1
33.3%
|
| Alanine aminotransferase increased |
1
25%
|
0
0%
|
| Electrocardiogram QT prolonged |
0
0%
|
1
33.3%
|
| Injury, Poisoning, and Procedural Complications |
0
0%
|
1
33.3%
|
| Contusion |
0
0%
|
1
33.3%
|
| Fall |
0
0%
|
1
33.3%
|
Adverse Events
| Time Frame | Adverse events (AEs) were collected from Induction phase Cycle 1, Day 1 up to 35 days after last completed cycle in Consolidation phase, up to approximately 1 year. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | A treatment-emergent AE was defined as an AE that emerges (or worsens) from the first dose of study drug and coadministered drugs to the follow-up visit, 35 days after the last dose of study drug and co-administered drugs, or the start date of new acute myeloid leukemia post-treatment, whichever was earlier. The serious AEs (SAEs) reported occurred only in the Induction phase. No SAEs occurred during the consolidation phase. TEAEs at ≥5% are reported for both induction and consolidation phases. | |||
| Arm/Group Title | Quizartinib 20 mg/Day | Quizartinib 40 mg/Day | ||
| Arm/Group Description | Participants who received 20 mg quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. | Participants who received 40 mg/day quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib. | ||
All Cause Mortality |
||||
| Quizartinib 20 mg/Day | Quizartinib 40 mg/Day | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/4 (0%) | 0/3 (0%) | ||
Serious Adverse Events |
||||
| Quizartinib 20 mg/Day | Quizartinib 40 mg/Day | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/4 (0%) | 2/3 (66.7%) | ||
| Infections and infestations | ||||
| Pneumonia | 0/4 (0%) | 1/3 (33.3%) | ||
| Staphylococcal bacteraemia | 0/4 (0%) | 1/3 (33.3%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Quizartinib 20 mg/Day | Quizartinib 40 mg/Day | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | 3/3 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile neutropenia | 4/4 (100%) | 3/3 (100%) | ||
| Anaemia | 2/4 (50%) | 1/3 (33.3%) | ||
| Leukopenia | 1/4 (25%) | 0/3 (0%) | ||
| Neutropenia | 1/4 (25%) | 0/3 (0%) | ||
| Thrombocytopenia | 1/4 (25%) | 0/3 (0%) | ||
| Cardiac disorders | ||||
| Palpitations | 0/4 (0%) | 1/3 (33.3%) | ||
| Eye disorders | ||||
| Photophobia | 1/4 (25%) | 0/3 (0%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 3/4 (75%) | 2/3 (66.7%) | ||
| Nausea | 3/4 (75%) | 2/3 (66.7%) | ||
| Abdominal pain upper | 3/4 (75%) | 1/3 (33.3%) | ||
| Stomatitis | 3/4 (75%) | 1/3 (33.3%) | ||
| Constipation | 1/4 (25%) | 2/3 (66.7%) | ||
| Cheilitis | 1/4 (25%) | 1/3 (33.3%) | ||
| Vomiting | 1/4 (25%) | 1/3 (33.3%) | ||
| Melaena | 0/4 (0%) | 1/3 (33.3%) | ||
| General disorders | ||||
| Oedema peripheral | 1/4 (25%) | 1/3 (33.3%) | ||
| Pyrexia | 0/4 (0%) | 1/3 (33.3%) | ||
| Hepatobiliary disorders | ||||
| Hepatic function abnormal | 0/4 (0%) | 1/3 (33.3%) | ||
| Immune system disorders | ||||
| Hypersensitivity | 0/4 (0%) | 1/3 (33.3%) | ||
| Infections and infestations | ||||
| Pneumonia | 1/4 (25%) | 0/3 (0%) | ||
| Skin infection | 1/4 (25%) | 1/3 (33.3%) | ||
| Lung infection | 0/4 (0%) | 1/3 (33.3%) | ||
| Upper respiratory tract infection | 1/4 (25%) | 0/3 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Contusion | 0/4 (0%) | 1/3 (33.3%) | ||
| Fall | 0/4 (0%) | 1/3 (33.3%) | ||
| Investigations | ||||
| Gamma-glutamyltransferase increased | 3/4 (75%) | 1/3 (33.3%) | ||
| Alanine aminotransferase increased | 2/4 (50%) | 1/3 (33.3%) | ||
| Electrocardiogram QT prolonged | 0/4 (0%) | 3/3 (100%) | ||
| Blood alkaline phosphatase increased | 1/4 (25%) | 1/3 (33.3%) | ||
| Platelet count decreased | 1/4 (25%) | 1/3 (33.3%) | ||
| Weight decreased | 1/4 (25%) | 1/3 (33.3%) | ||
| White blood cell count decreased | 1/4 (25%) | 1/3 (33.3%) | ||
| Aspartate aminotransferase | 1/4 (25%) | 0/3 (0%) | ||
| Aspartate aminotransferase increased | 0/4 (0%) | 1/3 (33.3%) | ||
| Blood bilirubin increased | 1/4 (25%) | 0/3 (0%) | ||
| Blood lactate dehydrogenase increased | 0/4 (0%) | 1/3 (33.3%) | ||
| Blood pressure decreased | 0/4 (0%) | 1/3 (33.3%) | ||
| Lipase increased | 0/4 (0%) | 1/3 (33.3%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 3/4 (75%) | 1/3 (33.3%) | ||
| Hypoalbuminaemia | 1/4 (25%) | 1/3 (33.3%) | ||
| Hypokalaemia | 2/4 (50%) | 0/3 (0%) | ||
| Hypomagnesaemia | 1/4 (25%) | 0/3 (0%) | ||
| Hyponatraemia | 1/4 (25%) | 0/3 (0%) | ||
| Hypophosphataemia | 1/4 (25%) | 0/3 (0%) | ||
| Hypouricaemia | 0/4 (0%) | 1/3 (33.3%) | ||
| Tumour lysis syndrome | 1/4 (25%) | 0/3 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 0/4 (0%) | 2/3 (66.7%) | ||
| Musculoskeletal pain | 0/4 (0%) | 1/3 (33.3%) | ||
| Myalgia | 1/4 (25%) | 0/3 (0%) | ||
| Pain in extremity | 0/4 (0%) | 1/3 (33.3%) | ||
| Nervous system disorders | ||||
| Dysgeusia | 3/4 (75%) | 1/3 (33.3%) | ||
| Dizziness | 1/4 (25%) | 0/3 (0%) | ||
| Renal and urinary disorders | ||||
| Haematuria | 1/4 (25%) | 0/3 (0%) | ||
| Proteinuria | 1/4 (25%) | 0/3 (0%) | ||
| Urinary tract pain | 1/4 (25%) | 0/3 (0%) | ||
| Reproductive system and breast disorders | ||||
| Menorrhagia | 0/4 (0%) | 1/3 (33.3%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Epistaxis | 0/4 (0%) | 1/3 (33.3%) | ||
| Oropharyngeal pain | 0/4 (0%) | 1/3 (33.3%) | ||
| Respiratory disorder | 0/4 (0%) | 1/3 (33.3%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 3/4 (75%) | 2/3 (66.7%) | ||
| Rash | 1/4 (25%) | 2/3 (66.7%) | ||
| Rash maculo-papular | 1/4 (25%) | 1/3 (33.3%) | ||
| Dermatitis bullous | 0/4 (0%) | 1/3 (33.3%) | ||
| Dry skin | 0/4 (0%) | 1/3 (33.3%) | ||
| Vascular disorders | ||||
| Hypotension | 0/4 (0%) | 1/3 (33.3%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Contact for Clinical Trial Information |
|---|---|
| Organization | Daiichi Sankyo, Inc. |
| Phone | 908-992-6400 |
| CTRinfo@dsi.com |
Responsible Party:
Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier:
NCT02834390
Other Study ID Numbers:
- AC220-A-J102
First Posted:
Jul 15, 2016
Last Update Posted:
Aug 19, 2021
Last Verified:
Jul 1, 2021