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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1163-2185 | Registry Identifier | WHO |
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Business Decision; No Safety or Efficacy Concerns.
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The purpose of the Phase 1b dose finding phase is to determine the safety, tolerability, and maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of TAK-659 in participants with relapsed or refractory AML. The purpose of the Phase 2 expansion phase is to evaluate preliminary efficacy of TAK-659 in relapsed or refractory AML as measured by overall response rate (ORR).
The drug being tested in this study is TAK-659. TAK-659 is being tested to treat people who have relapsed or refractory acute myelogenous leukemia (AML). This study will be conducted in 2 phases. The first phase will determine a safe and well-tolerated dose of TAK-659 to be used in the second phase, and the second phase will look at response to treatment in people who take TAK-659.
The study will enroll approximately 106 participants (approximately 40 in the first phase and 66 in the second phase). There will be two separate cohorts during Phase 2 portion of the study, one for participants with FLT-3 internal tandem duplication (ITD) mutations and the other for FLT-3 wild-type participants.
Phase 1b:
• TAK-659 60 milligram (mg) tablet starting dose escalated in 20 mg or higher increments to a maximum tolerated dose or RP2D
Phase 2:
• TAK-659 tablet at the maximum tolerated dose or RP2D determined in Phase 1b.
All participants will be asked to take their prescribed tablets at the same time each day throughout the study.
This multi-center trial will be conducted in the United States. The overall time to participate in this study is up to 24 months (12 months of treatment and 12 months of follow up) unless the treating physician believes the participant would continue to derive benefit from the study drug.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1b: TAK-659 | Experimental | TAK-659 tablets taken orally, once daily or twice daily on Days 1-28 in a 28 day cycle, for up to 12 cycles or until disease progression. Dosage of TAK-659 may increase in 20 mg increments using a 3 + 3 dose escalation design to determine a MTD and/or RP2D. |
|
| Phase 2: TAK-659 | Experimental | TAK-659, tablets taken orally, once daily or twice daily on Days 1-28 in a 28 day cycle, for up to 12 cycles or until disease progression. Dosage for this phase will be determined from results of Phase 1b MTD/RP2D. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAK-659 | Drug | TAK-659 tablets. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1b: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | AE meant any untoward medical occurrence in a participant or participant administered a pharmaceutical product; the untoward medical occurrence did not necessarily have a causal relationship with this treatment. SAE is any untoward medical occurrence that at any dose may result in death, life-threatening, required in participant hospitalization or prolongation of an existing hospitalization or can be a medically important event. TEAEs were defined as any AE that occurs after administration of the first dose of study treatment and up through 28 days after the last dose of study medication, or until the start of subsequent antineoplastic therapy, whichever occurs first. | From the first dose of study drug through 28 days after the last dose of study drug or until the start of subsequent antineoplastic therapy, whichever occurred first (Up to 13 months) |
| Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs) | Toxicity was evaluated according to the NCI CTCAE, v4.03. DLT was defined as any of the following considered related to any of the treatment, by investigator: Prolonged myelosuppression with persistence of Grade ≥4 neutropenia or thrombocytopenia in absence of leukemia (blast count <5% in bone marrow) ≥42 days after initiation of Cycle 1 therapy; Any Grade ≥3 nonhematologic toxicity with exceptions- Grade 3 nausea or emesis resolved to Grade ≤1 or baseline in a week after use of optimal antiemetic regimen. Grade 3 diarrhea that resolved to Grade ≤1 or baseline in a week after receiving maximal supportive therapy, Brief (<1 week) Grade 3 fatigue, Asymptomatic Grade 3 laboratory abnormalities that were not clinically significant; Failure to administer ≥75% of planned doses of study drug due to TAK-659 -related or possibly related hematological or nonhematologic toxicities; related Grade ≥2 nonhematologic toxicities that required dose reduction or discontinuation of therapy. | Up to Cycle 1 (28 days) |
| Phase 1b: Number of Participants With Clinically Significant Laboratory Findings Reported as TEAEs | Clinical laboratory evaluations were performed locally for Hematology, Serum Chemistry, Urinalysis. Any abnormal laboratory values were reported as a TEAE if that value led to discontinuation or delay in treatment, dose modification, therapeutic intervention, or was considered by the investigator to be a clinically significant change from Baseline. |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 2: Duration of Response (DOR) | DOR was defined as the time from the date of first documentation of a response to the date of first documented progressive disease (PD). PD was defined as >50% increase in bone marrow blasts from baseline value. | Up to 13 months |
| Phase 2: Time to Progression (TTP) |
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Inclusion Criteria:
Male or female participants 18 years or older.
Must have a histopathologically documented diagnosis of primary or secondary AML (excluding acute promyelocytic leukemia), as defined by World Health Organization (WHO) criteria (Jaffe et al, 2001), for whom no standard therapies are anticipated to result in a durable remission according to the clinical judgment of the principal investigator, or who refuses standard therapies (phase 1b and 2).
Participants for the phase 2 portion of the study must, in addition, meet the following:
o Must be refractory to or relapsed after no more than 2 prior chemotherapy regimens. Re-induction with the same regimen or stem cell transplant will not be considered a separate regimen.
Eastern Cooperative Oncology Group performance status of 0 to 1.
Female participants who:
Male participants, even if surgically sterilized (that is, status postvasectomy), who:
Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
In the absence of rapid progressive disease, the interval from prior systemic anticancer treatment to time of TAK-659 administration should be at least 2 weeks for cytotoxic agents (other than hydroxyurea), or at least 5 half-lives for noncytotoxic agents, and participants have to have recovered from acute toxicities of these therapies. Participants who are on hydroxyurea may be included in the study and may continue on hydroxyurea for the first 28 days while participating in this study.
Suitable venous access for the study-required blood sampling, including pharmacokinteic (PK) and pharmacodynamic (PD) sampling and blood transfusion support.
Clinical laboratory values as specified in the following:
Exclusion Criteria:
Clinically active central nervous system leukemia.
Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.
Any serious medical or psychiatric illness, including drug or alcohol abuse that could, in the investigator's opinion, potentially jeopardize the safety of the participant or interfere with the objectives of the study.
Systemic anti-cancer treatment (including investigational agents) <=21 days or <= 5*their half-lives before the first dose of study treatment. (For example, if the 5*the half-life is shorter than 21 days, 5*half-life should be used as the washout period. However, a minimum of 10 days should elapse from prior therapy to initiating protocol therapy).
Persistent clinically significant toxicity from prior chemotherapy that is Grade 2 or higher by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (v4.03).
Receipt of hematopoietic stem cell transplant (HSCT) within 60 days of the first dose of TAK-659; clinically significant graft-versus-host disease (GVHD) requiring ongoing immunosuppressive therapy post HSCT at the time of screening (use of topical steroids for ongoing skin GVHD is permitted).
Active, systemic infection requiring intravenous (IV) antibiotic, antifungal, or antiviral therapy or other serious infection within 14 days before the first dose of study drug.
Major surgery within 14 days before the first dose of study drug and have not recovered fully from any complications from surgery.
Radiotherapy less than 2 weeks before the first dose of study treatment or have not recovered from acute toxic effects from radiotherapy.
Known human immunodeficiency virus (HIV) positive (testing not required).
Known hepatitis B surface antigen-positive, known or suspected active hepatitis C infection (testing not required).
Evidence of currently uncontrolled cardiovascular conditions as listed in the protocol; acute myocardial infarction with 6 months before starting study drug; baseline QT interval (QTcF) greater than (>) 450 milliseconds (msec) (males) or > 475 msec (females); or abnormalities on baseline 12-lead electrocardiogram (ECG) that are considered clinically significant per investigator.
Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of TAK-659 including difficulty swallowing tablets; diarrhea > Grade 1 despite supportive therapy.
Use or consumption of any of the following substances:
White blood cell count > 50,000 per micro liter (/µL); hydroxyurea may be used to control the level of circulating leukemic blast cell counts prior to study entry and, if needed, concomitantly while on TAK-659 treatment during the first 28 days of the study. Hydroxyurea can be used up to a maximum dose of 5 gram per (g/) day.
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35233 | United States | ||
| Robert H. Lurie Comprehensive Cancer Center of Northwestern University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36226495 | Derived | Pratz KW, Kaplan J, Levy M, Bixby D, Burke PW, Erba H, Wise-Draper TM, Roboz GJ, Papadantonakis N, Rajkhowa T, Hernandez D, Dobler I, Gregory RC, Li C, Wang S, Stumpo K, Kannan K, Miao H, Levis M. A phase Ib trial of mivavotinib (TAK-659), a dual SYK/FLT3 inhibitor, in patients with relapsed/refractory acute myeloid leukemia. Haematologica. 2023 Mar 1;108(3):705-716. doi: 10.3324/haematol.2022.281216. |
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Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Participants with relapsed or refractory acute myelogenous leukemia(AML)were enrolled in dose escalation phase of study to receive TAK-659 to determine maximum tolerated dose/recommended phase 2 dose. In dose expansion phase(Phase 2), participants refractory to or relapsed after <=2 prior chemotherapy regimens and with no prior exposure to any investigational FLT-3 inhibitors were to be enrolled, however, as per Sponsor's decision, the study terminated before initiation of the Phase 2.
Participants took part in the study at 7 investigative sites in United States from 09 March 2015 to study end date:15 August 2018. An additional 8 sites were activated to participate in the Phase 2 expansion phase of the study, however, the Phase 2 portion of the study was not opened for enrollment.
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| ID | Title | Description |
|---|---|---|
| FG000 | TAK-659 60 mg QD | TAK-659, 60 mg tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| FG001 | TAK-659 100 mg QD |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 5, 2018 | Apr 14, 2021 |
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| From first dose of study drug through 28 days after the last dose of study drug or until the start of subsequent antineoplastic therapy, whichever occurred first (Up to 13 months) |
| Phase 1b: Number of Participants With Clinically Significant Vital Sign Findings Reported as TEAEs | Vital signs measurement (blood pressure, heart rate, and temperature) were performed before dosing on visit days and as clinically indicated. Any vital sign finding were reported as a TEAE if that value led to discontinuation or delay in treatment, dose modification, therapeutic intervention, or was considered by the investigator to be a clinically significant change from Baseline. | From first dose of study drug through 28 days after the last dose of study drug or until the start of subsequent antineoplastic therapy, whichever occurred first (Up to 13 months) |
| Phase 2: Overall Response Rate (ORR) | ORR was defined as percentage of participants who achieved complete response (CR), complete response with incomplete platelet recovery (CRp), incomplete hematologic recovery (CRi), partial hematologic recovery (CRh), composite complete remission (CRc), and partial response (PR) in response-evaluable population. CR: morphologic leukemia-free state and have absolute neutrophil count (ANC) of more than 1000/μL and platelets of ≥100,000/μL. CRp: satisfied all CR criteria except platelets <100,000/μL. CRi: fulfill all of the criteria for CR after chemotherapy except for residual neutropenia (<1000/μL) or thrombocytopenia (<100,000/μL). CRh: no evidence of peripheral blasts and partial recovery of peripheral blast counts including ANC above 500/μL and platelets above 50,000/μL. CRc: sum of participant achieving CR, CRh, CRi, or CRp. PR required all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in bone marrow aspirate. | Up to 13 months |
TTP was defined as the time from the date of first study drug administration to the date of first documentation of PD by the investigator. PD was defined as >50% increase in bone marrow blasts from baseline value. |
| Up to 13 months |
| Phase 2: Mortality Rate at Months 3 and 6 | Percentage of participants who died at Months 3 and 6. | Months 3 and 6 |
| Phase 2: Overall Survival (OS) | OS was defined as the time from the date of study entry to the date of death. | Up to 13 months |
| Phase 2: Overall Response Rate (ORR) in FLT-3-internal Tandem Duplication (ITD) Mutant Versus Wild Type (WT) Populations | ORR was defined as percentage of participants who achieved complete response (CR), complete response with incomplete platelet recovery (CRp), incomplete hematologic recovery (CRi), partial hematologic recovery (CRh), composite complete remission (CRc), and partial response (PR) in response-evaluable population. CR: morphologic leukemia-free state and have absolute neutrophil count (ANC) of more than 1000/μL and platelets of ≥100,000/μL. CRp: satisfied all CR criteria except platelets <100,000/μL. CRi: fulfill all of the criteria for CR after chemotherapy except for residual neutropenia (<1000/μL) or thrombocytopenia (<100,000/μL). CRh: no evidence of peripheral blasts and partial recovery of peripheral blast counts including ANC above 500/μL and platelets above 50,000/μL. CRc: sum of participant achieving CR, CRh, CRi, or CRp. PR required all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in bone marrow aspirate. | Days 22 to 28 of Cycles 1, 2, 4 and 5 (each cycle was of 28-days) |
| Phase 2: Duration of Response (DOR) in FLT-3-ITD Mutant Versus WT Populations | DOR was defined as the time from the date of first documentation of a response to the date of first documented PD. PD was defined as >50% increase in bone marrow blasts from baseline value. | Up to 13 months |
| Phase 2: Time to Progression (TTP) in FLT-3-ITD Mutant Versus WT Populations | TTP was defined as the time from the date of first study drug administration to the date of first documentation of PD by the investigator. PD was defined as >50% increase in bone marrow blasts from baseline value. | Up to 13 months |
| Phase 2: Mortality Rate in FLT-3-ITD Mutant Versus WT Populations | Number of participants who died at Months 3 and 6. | Months 3 and 6 |
| Phase 2: Overall Survival (OS) in FLT-3-ITD Mutant Versus WT Populations | OS was defined as the time from the date of study entry to the date of death. | Cycle 1 (28-day Cycle), Day 1 to 12 months |
| Phase 1: Cmax: Maximum Observed Plasma Concentration After Single Dose (Day 1) and Multiple Dose (Day 15) for TAK-659 | Cycle 1 (28-day cycle), Days 1 and 15 pre-dose and at multiple time points (Up to 24 hours for QD arms and Up to 8 hours for BID arms) post-dose |
| Phase 1: Tmax: Time to Reach the Maximum Observed Plasma Concentration After Single Dose (Day 1) and Multiple Dose (Day 15) for TAK-659 | Cycle 1 (28-day cycle), Days 1 and 15 pre-dose and at multiple time points (Up to 24 hours for QD arms and Up to 8 hours for BID arms) post-dose |
| Phase 1: AUC0-24: Area Under the Plasma Concentration-Time Curve During a Dosing Interval After Single Dose (Day 1) and Once-Daily (QD) Multiple Dose (Day 15) for TAK-659 | AUC0-24 was analyzed in the QD arms/cohorts as their sampling was done up to 24 hours. | Cycle 1 (28-day cycle), Days 1 and 15 pre-dose and at multiple time points (Up to 24 hours for QD arms) post-dose |
| Phase 1: AUC0-8: Area Under the Plasma Concentration-Time Curve During a Dosing Interval After Single Dose (Day 1) and Twice-Daily (BID) Multiple Dose (Day 15) for TAK-659 | AUC0-8 was analyzed in the BID arms/cohorts as their sampling was done up to 8 hours. | Cycle 1 (28-day cycle), Days 1 and 15 pre-dose and at multiple time points (Up to 8 hours for BID arms) post-dose |
| Phase 1: CL/Fss: Apparent Clearance After Extravascular Administration at Steady State After Once-Daily (QD) Multiple Dose (Day 15) for TAK-659 | Cycle 1 (28-day cycle), Day 15 pre-dose and at multiple time points (Up to 24 hours for QD arms) post-dose |
| Phase 1: Rac(AUC0-24): Accumulation Ratio Based on AUC0-24 After Once-Daily (QD) Multiple Dose (Day 15) for TAK-659 | Accumulation ratio (based on AUC0-24), calculated as AUC0-24 after multiple dosing (at steady state)/AUC0-24 after a single dose. | Cycle 1 (28-day cycle), Day 15 pre-dose and at multiple time points (up to 24 hours for QD arms) post-dose |
| Phase 1: Rac(AUC0-8): Accumulation Ratio Based on AUC0-8 After Twice-Daily (BID) Multiple Dose (Day 15) for TAK-659 | Accumulation ratio (based on AUC0-8), calculated as AUC0-8 after multiple dosing (at steady state)/AUC0-8 after a single dose. | Cycle 1 (28-day cycle), Day 15 pre-dose and at multiple time points (up to 8 hours for BID arms) post-dose |
| Phase 1: PTR: Peak Trough Ratio After Multiple Dose (Day 15) for TAK-659 | The ratio of the maximum observed plasma concentration to the observed trough plasma concentration, where trough concentration is the concentration at the end of the dosing interval at steady-state before the next dose is administered. | Cycle 1 (28-day cycle), Day 15 pre-dose and at multiple time points (Up to 24 hours for QD arms and Up to 8 hours for BID arms) post-dose |
| Chicago |
| Illinois |
| 60611 |
| United States |
| Oncology Specialists, S.C. | Niles | Illinois | 60714 | United States |
| Johns Hopkins Hospital | Baltimore | Maryland | 21287 | United States |
| Dana Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan | 48109 | United States |
| Karmanos Cancer Center | Detroit | Michigan | 48201 | United States |
| Henry Ford Health System | Detroit | Michigan | 48202 | United States |
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| North Shore Long Island Jewish Medical Center | New York | New York | 10024 | United States |
| University of North Carolina Hospital | Chapel Hill | North Carolina | 27514 | United States |
| UC Health Clinical Trials Office | Cincinnati | Ohio | 45206 | United States |
| Baylor University Medical Center | Dallas | Texas | 75204 | United States |
| Medical College of Wisconsin, Inc. | Milwaukee | Wisconsin | 53266 | United States |
| Queen Elizabeth II Health Sciences Centre | Halifax | Nova Scotia | B3H 3A7 | Canada |
| Princess Margaret Hospital | Toronto | Ontario | M5G 2M9 | Canada |
| Wake Forest University Baptist Medical Center | Toronto | Ontario | M5G 2M9 | Canada |
TAK-659, 100 mg tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| FG002 | TAK-659 120 mg QD | TAK-659, 120 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| FG003 | TAK-659 140 mg QD | TAK-659, 140 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| FG004 | TAK-659 160 mg QD | TAK-659, 160 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| FG005 | TAK-659 60 mg BID | TAK-659, 60 mg, tablets, orally, BID on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| FG006 | TAK-659 80 mg BID | TAK-659, 80 mg tablets, orally, BID on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| FG007 | Phase 2 (Dose Expansion Phase) | TAK-659 tablets at the maximum-tolerated dose (MTD)/recommended phase 2 dose (RP2D) determined from dose escalation phase, orally, QD or BID on Days 1 to 28 in each 28-day Cycle, for up to 12 cycles or until disease progression in participants who were to be entered in Phase 2. |
| COMPLETED |
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| NOT COMPLETED |
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Safety population included all enrolled participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | TAK-659 60 mg QD | TAK-659, 60 mg tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| BG001 | TAK-659 100 mg QD | TAK-659, 100 mg tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| BG002 | TAK-659 120 mg QD | TAK-659, 120 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| BG003 | TAK-659 140 mg QD | TAK-659, 140 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| BG004 | TAK-659 160 mg QD | TAK-659, 160 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| BG005 | TAK-659 60 mg BID | TAK-659, 60 mg, tablets, orally, BID on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| BG006 | TAK-659 80 mg BID | TAK-659, 80 mg tablets, orally, BID on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| BG007 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
| |||||||||||
| Region of Enrollment | Count of Participants | Participants |
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| Height | Number of participants analyzed is the number of participants with data available for height at Baseline. | Mean | Standard Deviation | cm |
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| Weight | Mean | Standard Deviation | kg |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||
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| Primary | Phase 1b: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | AE meant any untoward medical occurrence in a participant or participant administered a pharmaceutical product; the untoward medical occurrence did not necessarily have a causal relationship with this treatment. SAE is any untoward medical occurrence that at any dose may result in death, life-threatening, required in participant hospitalization or prolongation of an existing hospitalization or can be a medically important event. TEAEs were defined as any AE that occurs after administration of the first dose of study treatment and up through 28 days after the last dose of study medication, or until the start of subsequent antineoplastic therapy, whichever occurs first. | Safety population included all enrolled participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | From the first dose of study drug through 28 days after the last dose of study drug or until the start of subsequent antineoplastic therapy, whichever occurred first (Up to 13 months) |
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| Primary | Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs) | Toxicity was evaluated according to the NCI CTCAE, v4.03. DLT was defined as any of the following considered related to any of the treatment, by investigator: Prolonged myelosuppression with persistence of Grade ≥4 neutropenia or thrombocytopenia in absence of leukemia (blast count <5% in bone marrow) ≥42 days after initiation of Cycle 1 therapy; Any Grade ≥3 nonhematologic toxicity with exceptions- Grade 3 nausea or emesis resolved to Grade ≤1 or baseline in a week after use of optimal antiemetic regimen. Grade 3 diarrhea that resolved to Grade ≤1 or baseline in a week after receiving maximal supportive therapy, Brief (<1 week) Grade 3 fatigue, Asymptomatic Grade 3 laboratory abnormalities that were not clinically significant; Failure to administer ≥75% of planned doses of study drug due to TAK-659 -related or possibly related hematological or nonhematologic toxicities; related Grade ≥2 nonhematologic toxicities that required dose reduction or discontinuation of therapy. | DLT-evaluable population include all participants in the phase 1b portion of the study at each dose cohort who either experienced a DLT during Cycle 1 or completed at least 75% of planned doses of TAK-659 and had sufficient follow-up data to allow both the sponsor and investigators to determine whether a DLT occurred. | Posted | Count of Participants | Participants | Up to Cycle 1 (28 days) |
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| Primary | Phase 1b: Number of Participants With Clinically Significant Laboratory Findings Reported as TEAEs | Clinical laboratory evaluations were performed locally for Hematology, Serum Chemistry, Urinalysis. Any abnormal laboratory values were reported as a TEAE if that value led to discontinuation or delay in treatment, dose modification, therapeutic intervention, or was considered by the investigator to be a clinically significant change from Baseline. | Safety population included all enrolled participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | From first dose of study drug through 28 days after the last dose of study drug or until the start of subsequent antineoplastic therapy, whichever occurred first (Up to 13 months) |
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| Primary | Phase 1b: Number of Participants With Clinically Significant Vital Sign Findings Reported as TEAEs | Vital signs measurement (blood pressure, heart rate, and temperature) were performed before dosing on visit days and as clinically indicated. Any vital sign finding were reported as a TEAE if that value led to discontinuation or delay in treatment, dose modification, therapeutic intervention, or was considered by the investigator to be a clinically significant change from Baseline. | Safety population included all enrolled participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | From first dose of study drug through 28 days after the last dose of study drug or until the start of subsequent antineoplastic therapy, whichever occurred first (Up to 13 months) |
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| Primary | Phase 2: Overall Response Rate (ORR) | ORR was defined as percentage of participants who achieved complete response (CR), complete response with incomplete platelet recovery (CRp), incomplete hematologic recovery (CRi), partial hematologic recovery (CRh), composite complete remission (CRc), and partial response (PR) in response-evaluable population. CR: morphologic leukemia-free state and have absolute neutrophil count (ANC) of more than 1000/μL and platelets of ≥100,000/μL. CRp: satisfied all CR criteria except platelets <100,000/μL. CRi: fulfill all of the criteria for CR after chemotherapy except for residual neutropenia (<1000/μL) or thrombocytopenia (<100,000/μL). CRh: no evidence of peripheral blasts and partial recovery of peripheral blast counts including ANC above 500/μL and platelets above 50,000/μL. CRc: sum of participant achieving CR, CRh, CRi, or CRp. PR required all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in bone marrow aspirate. | This outcome measure was not analyzed as the expansion phase 2 portion of the study was not opened for enrollment and the planned analyses were not conducted due to early termination of study. | Posted | Up to 13 months |
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| Secondary | Phase 2: Duration of Response (DOR) | DOR was defined as the time from the date of first documentation of a response to the date of first documented progressive disease (PD). PD was defined as >50% increase in bone marrow blasts from baseline value. | This outcome measure was not analyzed as the expansion phase 2 portion of the study was not opened for enrollment and the planned analyses were not conducted due to early termination of study. | Posted | Up to 13 months |
|
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| Secondary | Phase 2: Time to Progression (TTP) | TTP was defined as the time from the date of first study drug administration to the date of first documentation of PD by the investigator. PD was defined as >50% increase in bone marrow blasts from baseline value. | This outcome measure was not analyzed as expansion phase 2 portion of the study was not opened for enrollment and planned analyses were not conducted due to early termination of study. | Posted | Up to 13 months |
|
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| Secondary | Phase 2: Mortality Rate at Months 3 and 6 | Percentage of participants who died at Months 3 and 6. | This outcome measure was not analyzed as the expansion phase 2 portion of the study was not opened for enrollment and planned analyses were not conducted due to early termination of study. | Posted | Months 3 and 6 |
|
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| Secondary | Phase 2: Overall Survival (OS) | OS was defined as the time from the date of study entry to the date of death. | This outcome measure was not analyzed as the expansion phase 2 portion of the study was not opened for enrollment and the planned analyses were not conducted due to early termination of study. | Posted | Up to 13 months |
|
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| Secondary | Phase 2: Overall Response Rate (ORR) in FLT-3-internal Tandem Duplication (ITD) Mutant Versus Wild Type (WT) Populations | ORR was defined as percentage of participants who achieved complete response (CR), complete response with incomplete platelet recovery (CRp), incomplete hematologic recovery (CRi), partial hematologic recovery (CRh), composite complete remission (CRc), and partial response (PR) in response-evaluable population. CR: morphologic leukemia-free state and have absolute neutrophil count (ANC) of more than 1000/μL and platelets of ≥100,000/μL. CRp: satisfied all CR criteria except platelets <100,000/μL. CRi: fulfill all of the criteria for CR after chemotherapy except for residual neutropenia (<1000/μL) or thrombocytopenia (<100,000/μL). CRh: no evidence of peripheral blasts and partial recovery of peripheral blast counts including ANC above 500/μL and platelets above 50,000/μL. CRc: sum of participant achieving CR, CRh, CRi, or CRp. PR required all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in bone marrow aspirate. | This outcome measure was not analyzed as the expansion phase 2 portion of the study was not opened for enrollment and the planned analyses were not conducted due to early termination of study. | Posted | Days 22 to 28 of Cycles 1, 2, 4 and 5 (each cycle was of 28-days) |
| ||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Phase 2: Duration of Response (DOR) in FLT-3-ITD Mutant Versus WT Populations | DOR was defined as the time from the date of first documentation of a response to the date of first documented PD. PD was defined as >50% increase in bone marrow blasts from baseline value. | This outcome measure was not analyzed as the expansion phase 2 portion of the study was not opened for enrollment and planned analyses were not conducted due to early termination of study. | Posted | Up to 13 months |
|
| |||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Phase 2: Time to Progression (TTP) in FLT-3-ITD Mutant Versus WT Populations | TTP was defined as the time from the date of first study drug administration to the date of first documentation of PD by the investigator. PD was defined as >50% increase in bone marrow blasts from baseline value. | This outcome measure was not analyzed as the expansion phase 2 portion of the study was not opened for enrollment and planned analyses were not conducted due to early termination of study. | Posted | Up to 13 months |
|
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| Secondary | Phase 2: Mortality Rate in FLT-3-ITD Mutant Versus WT Populations | Number of participants who died at Months 3 and 6. | This outcome measure was not analyzed as the expansion phase 2 portion of the study was not opened for enrollment and planned analyses were not conducted due to early termination of study. | Posted | Months 3 and 6 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Phase 2: Overall Survival (OS) in FLT-3-ITD Mutant Versus WT Populations | OS was defined as the time from the date of study entry to the date of death. | This outcome measure was not analyzed as expansion phase 2 portion of the study was not opened for enrollment and planned analyses were not conducted due to early termination of study. | Posted | Cycle 1 (28-day Cycle), Day 1 to 12 months |
|
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| Secondary | Phase 1: Cmax: Maximum Observed Plasma Concentration After Single Dose (Day 1) and Multiple Dose (Day 15) for TAK-659 | PK-evaluable population included all participants in the acute myelogenous leukemia dose escalation cohorts who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Number analyzed is the number of participants with data available for analysis at the given timepoint. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 1 (28-day cycle), Days 1 and 15 pre-dose and at multiple time points (Up to 24 hours for QD arms and Up to 8 hours for BID arms) post-dose |
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| Secondary | Phase 1: Tmax: Time to Reach the Maximum Observed Plasma Concentration After Single Dose (Day 1) and Multiple Dose (Day 15) for TAK-659 | PK-evaluable population included all participants in the acute myelogenous leukemia dose escalation cohorts who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Number analyzed is the number of participants with data available for analysis at the given timepoint. | Posted | Median | Full Range | hrs | Cycle 1 (28-day cycle), Days 1 and 15 pre-dose and at multiple time points (Up to 24 hours for QD arms and Up to 8 hours for BID arms) post-dose |
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| Secondary | Phase 1: AUC0-24: Area Under the Plasma Concentration-Time Curve During a Dosing Interval After Single Dose (Day 1) and Once-Daily (QD) Multiple Dose (Day 15) for TAK-659 | AUC0-24 was analyzed in the QD arms/cohorts as their sampling was done up to 24 hours. | Participants from PK-evaluable population included all participants in the acute myelogenous leukemia dose escalation cohorts who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters who received QD dosing of TAK-659. Number analyzed is the number of participants with data available for analysis at the given timepoint. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Cycle 1 (28-day cycle), Days 1 and 15 pre-dose and at multiple time points (Up to 24 hours for QD arms) post-dose |
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| Secondary | Phase 1: AUC0-8: Area Under the Plasma Concentration-Time Curve During a Dosing Interval After Single Dose (Day 1) and Twice-Daily (BID) Multiple Dose (Day 15) for TAK-659 | AUC0-8 was analyzed in the BID arms/cohorts as their sampling was done up to 8 hours. | Participants from PK-evaluable population included all participants in the acute myelogenous leukemia dose escalation cohorts who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters who received BID dosing of TAK-659. Number analyzed is number of participants with data available for analysis at the given time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Cycle 1 (28-day cycle), Days 1 and 15 pre-dose and at multiple time points (Up to 8 hours for BID arms) post-dose |
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| Secondary | Phase 1: CL/Fss: Apparent Clearance After Extravascular Administration at Steady State After Once-Daily (QD) Multiple Dose (Day 15) for TAK-659 | PK-evaluable population included all participants in the acute myelogenous leukemia dose escalation cohorts who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Overall number analyzed is the number of participants with data available for analysis at the given timepoint. Only QD dosing Cohorts were analyzed for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | Cycle 1 (28-day cycle), Day 15 pre-dose and at multiple time points (Up to 24 hours for QD arms) post-dose |
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| Secondary | Phase 1: Rac(AUC0-24): Accumulation Ratio Based on AUC0-24 After Once-Daily (QD) Multiple Dose (Day 15) for TAK-659 | Accumulation ratio (based on AUC0-24), calculated as AUC0-24 after multiple dosing (at steady state)/AUC0-24 after a single dose. | Participants from PK-evaluable population included all participants in the acute myelogenous leukemia dose escalation cohorts who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters who received QD dosing of TAK-659. Overall number analyzed are the number of participants with data available for analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Cycle 1 (28-day cycle), Day 15 pre-dose and at multiple time points (up to 24 hours for QD arms) post-dose |
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| Secondary | Phase 1: Rac(AUC0-8): Accumulation Ratio Based on AUC0-8 After Twice-Daily (BID) Multiple Dose (Day 15) for TAK-659 | Accumulation ratio (based on AUC0-8), calculated as AUC0-8 after multiple dosing (at steady state)/AUC0-8 after a single dose. | Participants from PK-evaluable population included all participants in the acute myelogenous leukemia dose escalation cohorts who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters who received BID dosing of TAK-659. Overall number analyzed are the number of participants with data available for analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Cycle 1 (28-day cycle), Day 15 pre-dose and at multiple time points (up to 8 hours for BID arms) post-dose |
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| Secondary | Phase 1: PTR: Peak Trough Ratio After Multiple Dose (Day 15) for TAK-659 | The ratio of the maximum observed plasma concentration to the observed trough plasma concentration, where trough concentration is the concentration at the end of the dosing interval at steady-state before the next dose is administered. | PK-evaluable population included all participants in the acute myelogenous leukemia dose escalation cohorts who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Overall number analyzed are the number of participants with data available for analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Cycle 1 (28-day cycle), Day 15 pre-dose and at multiple time points (Up to 24 hours for QD arms and Up to 8 hours for BID arms) post-dose |
|
From the first dose of study drug through 28 days after the last dose of study drug or until the start of subsequent antineoplastic therapy, whichever occurred first (Up to 13 months)
At each visit the investigator had to document any occurrence of adverse events and clinically significant abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TAK-659 60 mg QD | TAK-659, 60 mg tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. | 1 | 4 | 4 | 4 | 4 | 4 |
| EG001 | TAK-659 100 mg QD | TAK-659, 100 mg tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. | 3 | 7 | 6 | 7 | 7 | 7 |
| EG002 | TAK-659 120 mg QD | TAK-659, 120 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. | 3 | 4 | 4 | 4 | 4 | 4 |
| EG003 | TAK-659 140 mg QD | TAK-659, 140 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. | 4 | 5 | 5 | 5 | 5 | 5 |
| EG004 | TAK-659 160 mg QD | TAK-659, 160 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. | 7 | 9 | 9 | 9 | 9 | 9 |
| EG005 | TAK-659 60 mg BID | TAK-659, 60 mg, tablets, orally, BID on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. | 4 | 8 | 7 | 8 | 8 | 8 |
| EG006 | TAK-659 80 mg BID | TAK-659, 80 mg tablets, orally, BID on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. | 4 | 6 | 6 | 6 | 6 | 6 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Bronchopulmonary aspergillosis | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Enterococcal bacteraemia | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Enterococcal infection | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Adenovirus infection | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Anal abscess | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Bacterial sepsis | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Clostridium bacteraemia | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Clostridium difficile infection | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Device related infection | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Fungaemia | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Fungal infection | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Fusarium infection | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Infection | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Klebsiella infection | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Lung infection | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Parainfluenzae virus infection | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Periodontitis | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Periorbital cellulitis | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Pneumocystis jirovecii pneumonia | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Pneumonia escherichia | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Pneumonia fungal | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Pneumonia klebsiella | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Pneumonia necrotising | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Pneumonia staphylococcal | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Pulmonary mycosis | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Staphylococcal infection | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Staphylococcal sepsis | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Streptococcal sepsis | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | 21.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | 21.0 | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | 21.0 | Systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | 21.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | 21.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | 21.0 | Systematic Assessment |
| |
| Gastric haemorrhage | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Anal fistula | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Diarrhoea haemorrhagic | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Enteritis | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Gastritis haemorrhagic | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Haematemesis | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Haematochezia | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Pharyngeal stenosis | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Acute myeloid leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 21.0 | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | 21.0 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | 21.0 | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | 21.0 | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | 21.0 | Systematic Assessment |
| |
| Cardio-respiratory arrest | Cardiac disorders | 21.0 | Systematic Assessment |
| |
| Cardiogenic shock | Cardiac disorders | 21.0 | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | 21.0 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | 21.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | 21.0 | Systematic Assessment |
| |
| Death | General disorders | 21.0 | Systematic Assessment |
| |
| Fatigue | General disorders | 21.0 | Systematic Assessment |
| |
| Multiple organ dysfunction syndrome | General disorders | 21.0 | Systematic Assessment |
| |
| Amylase increased | Investigations | 21.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | 21.0 | Systematic Assessment |
| |
| Lactobacillus test positive | Investigations | 21.0 | Systematic Assessment |
| |
| Lipase increased | Investigations | 21.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | 21.0 | Systematic Assessment |
| |
| Respiratory syncytial virus test positive | Investigations | 21.0 | Systematic Assessment |
| |
| Transaminases increased | Investigations | 21.0 | Systematic Assessment |
| |
| Subdural haematoma | Injury, poisoning and procedural complications | 21.0 | Systematic Assessment |
| |
| Subarachnoid haemorrhage | Injury, poisoning and procedural complications | 21.0 | Systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | 21.0 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | 21.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | 21.0 | Systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | 21.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | 21.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Haemarthrosis | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | 21.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Gingival bleeding | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Melaena | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Mouth haemorrhage | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Haematochezia | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Abdominal pain lower | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Angina bullosa haemorrhagica | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Faeces discoloured | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Frequent bowel movements | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Glossodynia | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Hypoaesthesia oral | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Large intestine polyp | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Lip pain | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Oesophageal haemorrhage | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Oral mucosa haematoma | Gastrointestinal disorders | 21.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | 21.0 | Systematic Assessment |
| |
| Amylase increased | Investigations | 21.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | 21.0 | Systematic Assessment |
| |
| Lipase increased | Investigations | 21.0 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | 21.0 | Systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | 21.0 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | 21.0 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | 21.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | 21.0 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | 21.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | 21.0 | Systematic Assessment |
| |
| Blood calcium decreased | Investigations | 21.0 | Systematic Assessment |
| |
| Blood phosphorus decreased | Investigations | 21.0 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | 21.0 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | 21.0 | Systematic Assessment |
| |
| Ejection fraction decreased | Investigations | 21.0 | Systematic Assessment |
| |
| Troponin increased | Investigations | 21.0 | Systematic Assessment |
| |
| Blood potassium decreased | Investigations | 21.0 | Systematic Assessment |
| |
| Blood uric acid increased | Investigations | 21.0 | Systematic Assessment |
| |
| Clostridium test positive | Investigations | 21.0 | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | 21.0 | Systematic Assessment |
| |
| Enterococcus test positive | Investigations | 21.0 | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | 21.0 | Systematic Assessment |
| |
| Human rhinovirus test positive | Investigations | 21.0 | Systematic Assessment |
| |
| International normalised ratio increased | Investigations | 21.0 | Systematic Assessment |
| |
| Lymphocyte count increased | Investigations | 21.0 | Systematic Assessment |
| |
| Pseudomonas test positive | Investigations | 21.0 | Systematic Assessment |
| |
| Respirovirus test positive | Investigations | 21.0 | Systematic Assessment |
| |
| Staphylococcus test positive | Investigations | 21.0 | Systematic Assessment |
| |
| Streptococcus test positive | Investigations | 21.0 | Systematic Assessment |
| |
| Urine output increased | Investigations | 21.0 | Systematic Assessment |
| |
| Weight increased | Investigations | 21.0 | Systematic Assessment |
| |
| Fatigue | General disorders | 21.0 | Systematic Assessment |
| |
| Chills | General disorders | 21.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | 21.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | 21.0 | Systematic Assessment |
| |
| Pain | General disorders | 21.0 | Systematic Assessment |
| |
| Asthenia | General disorders | 21.0 | Systematic Assessment |
| |
| Face oedema | General disorders | 21.0 | Systematic Assessment |
| |
| Chest discomfort | General disorders | 21.0 | Systematic Assessment |
| |
| Facial pain | General disorders | 21.0 | Systematic Assessment |
| |
| Feeling abnormal | General disorders | 21.0 | Systematic Assessment |
| |
| Influenza like illness | General disorders | 21.0 | Systematic Assessment |
| |
| Malaise | General disorders | 21.0 | Systematic Assessment |
| |
| Swelling | General disorders | 21.0 | Systematic Assessment |
| |
| Unevaluable event | General disorders | 21.0 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Fluid overload | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Hyperamylasaemia | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Hyperlipasaemia | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Hypernatraemia | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Hyperphosphataemia | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Hypervolaemia | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Malnutrition | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Vitamin D deficiency | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Pulmonary mass | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Pharyngeal haemorrhage | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Lung infiltration | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Nasal dryness | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Nasal oedema | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Paranasal sinus discomfort | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Pharyngeal ulceration | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Sneezing | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | 21.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | 21.0 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | 21.0 | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | 21.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | 21.0 | Systematic Assessment |
| |
| Tremor | Nervous system disorders | 21.0 | Systematic Assessment |
| |
| Amnesia | Nervous system disorders | 21.0 | Systematic Assessment |
| |
| Cerebral haemorrhage | Nervous system disorders | 21.0 | Systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | 21.0 | Systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | 21.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | 21.0 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | 21.0 | Systematic Assessment |
| |
| Sinus headache | Nervous system disorders | 21.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | 21.0 | Systematic Assessment |
| |
| Hypogeusia | Nervous system disorders | 21.0 | Systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
| |
| Swelling face | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
| |
| Purpura | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
| |
| Blister | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
| |
| Dermatitis | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
| |
| Dermatitis exfoliative generalised | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
| |
| Hypersensitivity vasculitis | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
| |
| Rash generalised | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
| |
| Rash macular | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | 21.0 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | 21.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | 21.0 | Systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | 21.0 | Systematic Assessment |
| |
| Increased tendency to bruise | Blood and lymphatic system disorders | 21.0 | Systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | 21.0 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | 21.0 | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | 21.0 | Systematic Assessment |
| |
| Splenic lesion | Blood and lymphatic system disorders | 21.0 | Systematic Assessment |
| |
| Thrombocytosis | Blood and lymphatic system disorders | 21.0 | Systematic Assessment |
| |
| Periorbital oedema | Eye disorders | 21.0 | Systematic Assessment |
| |
| Eyelid oedema | Eye disorders | 21.0 | Systematic Assessment |
| |
| Retinal haemorrhage | Eye disorders | 21.0 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | 21.0 | Systematic Assessment |
| |
| Cataract | Eye disorders | 21.0 | Systematic Assessment |
| |
| Dry eye | Eye disorders | 21.0 | Systematic Assessment |
| |
| Eye swelling | Eye disorders | 21.0 | Systematic Assessment |
| |
| Conjunctival haemorrhage | Eye disorders | 21.0 | Systematic Assessment |
| |
| Macular fibrosis | Eye disorders | 21.0 | Systematic Assessment |
| |
| Ocular hyperaemia | Eye disorders | 21.0 | Systematic Assessment |
| |
| Scleral hyperaemia | Eye disorders | 21.0 | Systematic Assessment |
| |
| Scleral oedema | Eye disorders | 21.0 | Systematic Assessment |
| |
| Vitreous floaters | Eye disorders | 21.0 | Systematic Assessment |
| |
| Clostridium difficile infection | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Cytomegalovirus infection | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Acinetobacter bacteraemia | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Adenovirus infection | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Alpha haemolytic streptococcal infection | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Appendicitis | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Chronic sinusitis | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Device related infection | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Escherichia bacteraemia | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Fungal infection | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Fungal skin infection | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Osteomyelitis | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Sinusitis fungal | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Streptococcal bacteraemia | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Tonsillitis | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Urinary tract infection bacterial | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Bone cyst | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Chest wall haematoma | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Joint range of motion decreased | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Joint swelling | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Kyphosis | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Myopathy | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Pain in jaw | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Spinal osteoarthritis | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Spinal pain | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | 21.0 | Systematic Assessment |
| |
| Laceration | Injury, poisoning and procedural complications | 21.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | 21.0 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | 21.0 | Systematic Assessment |
| |
| Muscle strain | Injury, poisoning and procedural complications | 21.0 | Systematic Assessment |
| |
| Post procedural contusion | Injury, poisoning and procedural complications | 21.0 | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | 21.0 | Systematic Assessment |
| |
| Procedural site reaction | Injury, poisoning and procedural complications | 21.0 | Systematic Assessment |
| |
| Wound | Injury, poisoning and procedural complications | 21.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | 21.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | 21.0 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | 21.0 | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | 21.0 | Systematic Assessment |
| |
| Agitation | Psychiatric disorders | 21.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | 21.0 | Systematic Assessment |
| |
| Disorientation | Psychiatric disorders | 21.0 | Systematic Assessment |
| |
| Mental fatigue | Psychiatric disorders | 21.0 | Systematic Assessment |
| |
| Sleep disorder | Psychiatric disorders | 21.0 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | 21.0 | Systematic Assessment |
| |
| Pericardial effusion | Cardiac disorders | 21.0 | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | 21.0 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | 21.0 | Systematic Assessment |
| |
| Bundle branch block left | Cardiac disorders | 21.0 | Systematic Assessment |
| |
| Cardiomyopathy | Cardiac disorders | 21.0 | Systematic Assessment |
| |
| Supraventricular extrasystoles | Cardiac disorders | 21.0 | Systematic Assessment |
| |
| Ventricular tachycardia | Cardiac disorders | 21.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | 21.0 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | 21.0 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | 21.0 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | 21.0 | Systematic Assessment |
| |
| Nocturia | Renal and urinary disorders | 21.0 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | 21.0 | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | 21.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | 21.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | 21.0 | Systematic Assessment |
| |
| Flushing | Vascular disorders | 21.0 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | 21.0 | Systematic Assessment |
| |
| Pallor | Vascular disorders | 21.0 | Systematic Assessment |
| |
| Deafness | Ear and labyrinth disorders | 21.0 | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | 21.0 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | 21.0 | Systematic Assessment |
| |
| Adrenal insufficiency | Endocrine disorders | 21.0 | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | 21.0 | Systematic Assessment |
| |
| Hepatic lesion | Hepatobiliary disorders | 21.0 | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | 21.0 | Systematic Assessment |
| |
| Lipoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 21.0 | Systematic Assessment |
| |
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 21.0 | Systematic Assessment |
| |
| Acquired hydrocele | Reproductive system and breast disorders | 21.0 | Systematic Assessment |
| |
| Testicular oedema | Reproductive system and breast disorders | 21.0 | Systematic Assessment |
| |
| Vulvovaginal discomfort | Reproductive system and breast disorders | 21.0 | Systematic Assessment |
| |
| Vulvovaginal erythema | Reproductive system and breast disorders | 21.0 | Systematic Assessment |
|
In general, investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Takeda | +1-877-825-3327 | TrialDisclosures@takeda.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 8, 2018 | Apr 14, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000620859 | TAK-659 |
Not provided
Not provided
Not provided
|
|
|
|
|
|
|
| SAEs |
|
| OG001 | TAK-659 100 mg QD | TAK-659, 100 mg tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG002 | TAK-659 120 mg QD | TAK-659, 120 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG003 | TAK-659 140 mg QD | TAK-659, 140 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG004 | TAK-659 160 mg QD | TAK-659, 160 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG005 | TAK-659 60 mg BID | TAK-659, 60 mg, tablets, orally, BID on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG006 | TAK-659 80 mg BID | TAK-659, 80 mg tablets, orally, BID on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
|
|
TAK-659, 120 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG003 | TAK-659 140 mg QD | TAK-659, 140 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG004 | TAK-659 160 mg QD | TAK-659, 160 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG005 | TAK-659 60 mg BID | TAK-659, 60 mg, tablets, orally, BID on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG006 | TAK-659 80 mg BID | TAK-659, 80 mg tablets, orally, BID on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
|
|
TAK-659, 120 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG003 | TAK-659 140 mg QD | TAK-659, 140 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG004 | TAK-659 160 mg QD | TAK-659, 160 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG005 | TAK-659 60 mg BID | TAK-659, 60 mg, tablets, orally, BID on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG006 | TAK-659 80 mg BID | TAK-659, 80 mg tablets, orally, BID on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| OG003 | TAK-659 140 mg QD | TAK-659, 140 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG004 | TAK-659 160 mg QD | TAK-659, 160 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG005 | TAK-659 60 mg BID | TAK-659, 60 mg, tablets, orally, BID on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG006 | TAK-659 80 mg BID | TAK-659, 80 mg tablets, orally, BID on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
|
|
| OG003 | TAK-659 140 mg QD | TAK-659, 140 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG004 | TAK-659 160 mg QD | TAK-659, 160 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG005 | TAK-659 60 mg BID | TAK-659, 60 mg, tablets, orally, BID on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG006 | TAK-659 80 mg BID | TAK-659, 80 mg tablets, orally, BID on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
|
|
TAK-659, 120 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG003 | TAK-659 140 mg QD | TAK-659, 140 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG004 | TAK-659 160 mg QD | TAK-659, 160 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
|
|
| Units | Counts |
|---|
| Participants |
|
|
| OG003 | TAK-659 140 mg QD | TAK-659, 140 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG004 | TAK-659 160 mg QD | TAK-659, 160 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
|
|
TAK-659, 120 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles.
| OG003 | TAK-659 140 mg QD | TAK-659, 140 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG004 | TAK-659 160 mg QD | TAK-659, 160 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
|
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
TAK-659, 120 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG003 | TAK-659 140 mg QD | TAK-659, 140 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG004 | TAK-659 160 mg QD | TAK-659, 160 mg, tablets, orally, QD on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG005 | TAK-659 60 mg BID | TAK-659, 60 mg, tablets, orally, BID on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
| OG006 | TAK-659 80 mg BID | TAK-659, 80 mg tablets, orally, BID on Days 1 to 28 in each 28-day Cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 12 cycles. |
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