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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1169-6648 | Registry Identifier | WHO | |
| 2016-004132-37 | EudraCT Number |
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The purpose of this study is to assess the mass balance (that is, cumulative excretion of total radioactivity [TRA] in urine and feces) and to characterize the pharmacokinetics (PK) of pevonedistat in whole blood, plasma, and urine, and of TRA in plasma and whole blood following a single 1-hour infusion of 25 milligram per square meter (mg/m^2) [14C]-pevonedistat intravenous (IV) solution containing approximately 60 to 85 microcurie (mCi) (approximately 2.22-3.145 megabecquerel [MBq]) of TRA in participants with advanced solid tumors in Part A.
The drug being tested in this study is called Pevonedistat. Pevonedistat is being tested to treat people with advanced solid tumors.
The study will enroll approximately 4 to 6 pharmacokinetics (PK)-evaluable participants in part A. After completion of the mass balance and absorption, distribution, metabolism, excretion (ADME) assessment in Part A of the study, eligible participants will have the opportunity to continue into Part B at a secondary study site, which would begin in approximately 2 weeks of completion of Part A.
All participants will receive study drug via intravenous route. This multi-center trial will be conducted in Hungary. Participants will remain confined to the study site for 9 to 14 days in Part A. Participation in Part B is optional, participants will be re-evaluated for inclusion/exclusion criteria before administrating treatment. Participants will undergo treatment in Part B for a maximum of 12 cycles (21 days cycle each) and will include approximately 36 weeks for Part A and B combined. Participants will attend an end of study visit 30 days after the last dose of study drug in both Part A and B.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| [14C]-Pevonedistat 25 mg/m^2 | Experimental | [14C]-pevonedistat (containing approximately 60-98 mCi [approximately 2.22-3.626 MBq] of radioactive tracer), infusion, intravenously, single dose on Day 1 of Week 1 in Part A. After completion of Part A, participants will have opportunity to continue into Part B. Participant will receive Pevonedistat 25 mg/m^2, infusion, intravenously, single dose on Days 1, 3 and 5 of each 21 day cycle, for up to 12 cycles along with docetaxel 75 mg/m^2, infusion, intravenously, over 1 hour on Day 1 of each 21 day cycle; or pevonedistat 20 mg/m^2, infusion, intravenously, single dose on Days 1, 3 and 5 of each 21 day cycle, for up to 12 cycles, followed by paclitaxel 175 mg/m^2, infusion, intravenously, over 3 hours along with carboplatin 20 mg/m^2, infusion, intravenously, over 30 minutes on Day 1 of 21 each cycle up to 12 cycles. Based on investigator and sponsor discretion, participants deriving benefits will continue to receive current combination therapy or pevonedistat alone beyond 12 cycles. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pevonedistat | Drug | Pevonedistat intravenous infusion. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Cmax: Maximum Observed Plasma and Whole Blood Concentration for Pevonedistat | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose | |
| Part A: Tmax: Time to Reach the Maximum Plasma and Whole Blood Concentration (Cmax) for Pevonedistat | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose | |
| Part A: AUClast: Area Under the Plasma and Whole Blood Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Pevonedistat | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose | |
| Part A: Cmax: Maximum Observed Plasma and Whole Blood TRA Concentration for [14C]-Pevonedistat Drug-related Material | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose | |
| Part A: Tmax: Time to Reach the Maximum Plasma and Whole Blood TRA Concentration (Cmax) for [14C]-Pevonedistat Drug-related Material | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose | |
| Part A: AUClast: Area Under the Plasma and Whole Blood TRA Concentration Curve From Time 0 to Time of the Last Quantifiable Concentration for [14C]-Pevonedistat Drug-related Material | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose | |
| Part A: Aeurine,14C: Cumulative Amount of [14C]-Pevonedistat Excreted in Urine up to the Last Sampling Interval | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose | |
| Part A: Aefeces,14C: Cumulative Amount of [14C]-Pevonedistat Excreted in Feces up to the Last Sampling Interval |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Part A: From first dose of study drug in Part A up to Day 31; Part B: From first dose of study drug in Part B up to Cycle 11 Day 35 (Cycle length is equal to [=] 21 days) | |
| Part A: Percent Distribution of Total Radioactivity (TRA) for Pevonedistat and Its Metabolites in Plasma, Urine and Feces |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Millennium Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Magyar Honvédség Egészségügyi Központ Onkológiai osztály | Budapest | 1062 | Hungary | |||
| PRA Magyarország Kft. Fázis I-es Klinikai Farmakológiai Vizsgálóhely |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33089874 | Derived | Zhou X, Sedarati F, Faller DV, Zhao D, Faessel HM, Chowdhury S, Bolleddula J, Li Y, Venkatakrishnan K, Papai Z. Phase I study assessing the mass balance, pharmacokinetics, and excretion of [14C]-pevonedistat, a NEDD8-activating enzyme inhibitor in patients with advanced solid tumors. Invest New Drugs. 2021 Apr;39(2):488-498. doi: 10.1007/s10637-020-01017-x. Epub 2020 Oct 22. |
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Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
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Participants with advanced solid tumors were enrolled in this two-part study to receive intravenous infusion of pevonedistat in Part A and pevonedistat in combination with chemotherapy in Part B (optional part). One participant from Part A consented for Part B but did not meet the eligibility criteria and never received study treatment in Part B.
Participants took part in the study at 1 investigative site in Hungary from 11 May 2017 to 05 November 2018.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A: [14C]-Pevonedistat 25 mg/m^2 | [14C]-pevonedistat (containing approximately 60-98 microcurie [mCi] [approximately 2.22-3.626 megabecquerel (MBq)] of radioactive tracer), infusion, intravenously, single dose on Day 1 of Week 1 in Part A. |
| FG001 | Part B: Pevonedistat + Paclitaxel and Carboplatin | Pevonedistat 20 mg/m^2, infusion, intravenously, single dose, on Days 1, 3 and 5 of each 21-days treatment cycle (up to 11 cycles), in combination with paclitaxel 175 mg/m^2, infusion, intravenously along with carboplatin AUC5, infusion, intravenously, on Day 1 of each 21-days treatment cycle (up to 11 cycles). Pevonedistat was administered after the paclitaxel and carboplatin chemotherapy. Participants who completed Part A and provided consent for Part B continued treatment in Part B. |
| FG002 | Part B: Pevonedistat + Docetaxel | Pevonedistat 25 mg/m^2, infusion, intravenously, single dose on Days 1, 3 and 5 of each 21-days treatment cycle (up to 11 cycles), in combination with docetaxel 75 mg/m^2, infusion, intravenously, on Day 1 of each 21-days treatment cycle (up to 11 cycles). Pevonedistat was administered after the docetaxel chemotherapy. Participants who completed Part A and provided consent for Part B continued treatment in Part B. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A |
| |||||||||||||
| Part B |
|
The safety analysis set is defined as all enrolled participants who received at least 1 dose of [14C]-pevonedistat during Part A.
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| ID | Title | Description |
|---|---|---|
| BG000 | [14C]-Pevonedistat 25 mg/m^2 | [14C]-pevonedistat (containing approximately 60-98 mCi [approximately 2.22-3.626 MBq] of radioactive tracer), infusion, intravenously, single dose on Day 1 of Week 1 in Part A. Participants who completed Part A and provided consent for Part B continued treatment in Part B. Participants received pevonedistat 20 mg/m^2, infusion, intravenously, single dose, on Days 1, 3 and 5 of each 21-days treatment cycle (up to 11 cycles), in combination with paclitaxel 175 mg/m^2, infusion, intravenously along with carboplatin AUC5, infusion, intravenously, on Day 1 of each 21-days treatment cycle (up to 11 cycles); or pevonedistat 25 mg/m^2, infusion, intravenously, single dose on Days 1, 3 and 5 of each 21-days treatment cycle (up to 11 cycles), in combination with docetaxel 75 mg/m^2, infusion, intravenously, on Day 1 of each 21-days treatment cycle (up to 11 cycles). Pevonedistat was administered after the chemotherapies in Part B. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | The safety analysis set is defined as all enrolled participants who received at least 1 dose of [14C]-pevonedistat during Part A. |
| 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 | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Part A: Cmax: Maximum Observed Plasma and Whole Blood Concentration for Pevonedistat | The pharmacokinetic (PK) evaluable population included all enrolled participants who received the protocol-specified single [14C]-pevonedistat dose in Part A and did not receive any excluded medications throughout the completion of Part A and had sufficient concentration-time data. | Posted | Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
|
Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (From first dose of study drug in Part A up to Day 31; From first dose of study drug in Part B up to Cycle 11 Day 35)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Reported AEs and deaths are TEAEs that occurred between the first dose of the study drug and 30 days after the last dose of the study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A: [14C]-Pevonedistat 25 mg/m^2 | [14C]-pevonedistat (containing approximately 60-98 mCi [approximately 2.22-3.626 MBq] of radioactive tracer), infusion, intravenously, single dose on Day 1 of Week 1 in Part A. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| SARCOMA | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (21.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 19, 2018 | Feb 6, 2019 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Nov 29, 2016 | Feb 6, 2019 | Prot_001.pdf |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C539933 | pevonedistat |
| D000077143 | Docetaxel |
| D016190 | Carboplatin |
| D017239 | Paclitaxel |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
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| [14C]-Pevonedistat | Drug | [14C]-Pevonedistat intravenous infusion. |
|
| Docetaxel | Drug | Docetaxel intravenous infusion. |
|
| Carboplatin | Drug | Carboplatin intravenous infusion. |
|
| Paclitaxel | Drug | Paclitaxel intravenous infusion. |
|
| Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
| Part A: Aetotal,14C: Total Cumulative Excretion of [14C]-Pevonedistat From the Body | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
| Part A: Aeurine: Cumulative Amount of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
| Part A: Feurine: Cumulative Percentage of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
| Part A: Renal Clearance (CLR) for Pevonedistat | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
| Up to 168 hours post-dose |
| Part B: Number of Participants With Best Overall Response as Per Investigator's Assessment | The best overall response was defined as the participants with best response among complete response (CR) or partial response (PR) or stable disease (SD), or progressive disease (PD). It was assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than (<) 10 millimeter (mm). PR: at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters as the best overall response after randomization. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). | Up to Cycle 11 (Cycle length =21 days) |
| Budapest |
| 1076 |
| Hungary |
| NOT COMPLETED |
|
| Mean |
| Standard Deviation |
| years |
|
| Sex: Female, Male | The safety analysis set for Part A is defined as all enrolled participants who received at least 1 dose of [14C]-pevonedistat during Part A. All safety analyses in Part A was performed using the safety population for Part A. | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | The safety analysis set for Part A is defined as all enrolled participants who received at least 1 dose of [14C]-pevonedistat during Part A. All safety analyses in Part A was performed using the safety population for Part A. | Count of Participants | Participants |
|
| Race (NIH/OMB) | The safety analysis set for Part A is defined as all enrolled participants who received at least 1 dose of [14C]-pevonedistat during Part A. All safety analyses in Part A was performed using the safety population for Part A. | Count of Participants | Participants |
|
| Region of Enrollment | The safety analysis set for Part A is defined as all enrolled participants who received at least 1 dose of [14C]-pevonedistat during Part A. All safety analyses in Part A was performed using the safety population for Part A. | Count of Participants | Participants |
|
| Weight | The safety analysis set for Part A is defined as all enrolled participants who received at least 1 dose of [14C]-pevonedistat during Part A. All safety analyses in Part A was performed using the safety population for Part A. | Mean | Standard Deviation | kilogram (kg) |
|
| Height | The safety analysis set for Part A is defined as all enrolled participants who received at least 1 dose of [14C]-pevonedistat during Part A. All safety analyses in Part A was performed using the safety population for Part A. | Mean | Standard Deviation | centimeter (cm) |
|
| Body Mass Index (BMI) | The safety analysis set for Part A is defined as all enrolled participants who received at least 1 dose of [14C]-pevonedistat during Part A. All safety analyses in Part A was performed using the safety population for Part A. | Mean | Standard Deviation | kilogram per square meter (kg/m^2) |
|
| Body Surface Area (BSA) | The safety analysis set for Part A is defined as all enrolled participants who received at least 1 dose of [14 C]-pevonedistat during Part A. All safety analyses in Part A was performed using the safety population for Part A. | Mean | Standard Deviation | square meter (m^2) |
|
| Units | Counts |
|---|
| Participants |
|
|
| Primary | Part A: Tmax: Time to Reach the Maximum Plasma and Whole Blood Concentration (Cmax) for Pevonedistat | The PK evaluable population included all enrolled participants who received the protocol-specified single [14C]-pevonedistat dose in Part A and did not receive any excluded medications throughout the completion of Part A and had sufficient concentration-time data. | Posted | Median | Full Range | hour | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
|
|
|
| Primary | Part A: AUClast: Area Under the Plasma and Whole Blood Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Pevonedistat | The PK evaluable population included all enrolled participants who received the protocol-specified single [14C]-pevonedistat dose in Part A and did not receive any excluded medications throughout the completion of Part A and had sufficient concentration-time data. | Posted | Mean | Standard Deviation | hour*nanogram per milliliter (hr*ng/mL) | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
|
|
|
| Primary | Part A: Cmax: Maximum Observed Plasma and Whole Blood TRA Concentration for [14C]-Pevonedistat Drug-related Material | The PK evaluable population included all enrolled participants who received the protocol-specified single [14C]-pevonedistat dose in Part A and did not receive any excluded medications throughout the completion of Part A and had sufficient concentration-time data. | Posted | Mean | Standard Deviation | nanogram equivalent per milliliter | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
|
|
|
| Primary | Part A: Tmax: Time to Reach the Maximum Plasma and Whole Blood TRA Concentration (Cmax) for [14C]-Pevonedistat Drug-related Material | The PK evaluable population included all enrolled participants who received the protocol-specified single [14C]-pevonedistat dose in Part A and did not receive any excluded medications throughout the completion of Part A and had sufficient concentration-time data. | Posted | Median | Full Range | hour | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
|
|
|
| Primary | Part A: AUClast: Area Under the Plasma and Whole Blood TRA Concentration Curve From Time 0 to Time of the Last Quantifiable Concentration for [14C]-Pevonedistat Drug-related Material | The PK evaluable population included all enrolled participants who received the protocol-specified single [14C]-pevonedistat dose in Part A and did not receive any excluded medications throughout the completion of Part A and had sufficient concentration-time data. | Posted | Mean | Standard Deviation | hour*nanogram equivalent per milliliter | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
|
|
|
| Primary | Part A: Aeurine,14C: Cumulative Amount of [14C]-Pevonedistat Excreted in Urine up to the Last Sampling Interval | The PK evaluable population included all enrolled participants who received the protocol-specified single [14C]-pevonedistat dose in Part A and did not receive any excluded medications throughout the completion of Part A and had sufficient concentration-time data. | Posted | Mean | Standard Deviation | microgram equivalent (mcg eq) | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
|
|
|
| Primary | Part A: Aefeces,14C: Cumulative Amount of [14C]-Pevonedistat Excreted in Feces up to the Last Sampling Interval | The PK evaluable population included all enrolled participants who received the protocol-specified single [14C]-pevonedistat dose in Part A and did not receive any excluded medications throughout the completion of Part A and had sufficient concentration-time data. | Posted | Mean | Standard Deviation | mcg eq | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
|
|
|
| Primary | Part A: Aetotal,14C: Total Cumulative Excretion of [14C]-Pevonedistat From the Body | The PK evaluable population included all enrolled participants who received the protocol-specified single [14C]-pevonedistat dose in Part A and did not receive any excluded medications throughout the completion of Part A and had sufficient concentration-time data. | Posted | Mean | Standard Deviation | mcg eq | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
|
|
|
| Primary | Part A: Aeurine: Cumulative Amount of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose | The PK evaluable population included all enrolled participants who received the protocol-specified single [14C]-pevonedistat dose in Part A and did not receive any excluded medications throughout the completion of Part A and had sufficient concentration-time data. | Posted | Mean | Standard Deviation | microgram (mcg) | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
|
|
|
| Primary | Part A: Feurine: Cumulative Percentage of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose | The PK evaluable population included all enrolled participants who received the protocol-specified single [14C]-pevonedistat dose in Part A and did not receive any excluded medications throughout the completion of Part A and had sufficient concentration-time data. | Posted | Mean | Standard Deviation | percentage of dose | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
|
|
|
| Primary | Part A: Renal Clearance (CLR) for Pevonedistat | The PK evaluable population included all enrolled participants who received the protocol-specified single [14C]-pevonedistat dose in Part A and did not receive any excluded medications throughout the completion of Part A and had sufficient concentration-time data. | Posted | Mean | Standard Deviation | liter per hour (L/hr) | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
|
|
|
| Secondary | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | The safety analysis set is defined as all enrolled participants who received at least 1 dose of [14C]-pevonedistat during Part A. | Posted | Count of Participants | Participants | Part A: From first dose of study drug in Part A up to Day 31; Part B: From first dose of study drug in Part B up to Cycle 11 Day 35 (Cycle length is equal to [=] 21 days) |
|
|
|
| Secondary | Part A: Percent Distribution of Total Radioactivity (TRA) for Pevonedistat and Its Metabolites in Plasma, Urine and Feces | The PK evaluable population included all enrolled participants who received the protocol-specified single [14C]-pevonedistat dose in Part A and did not received any excluded medications throughout the completion of Part A and had sufficient concentration-time data. | Posted | Mean | Standard Deviation | percentage distribution of TRA | Up to 168 hours post-dose |
|
|
|
| Secondary | Part B: Number of Participants With Best Overall Response as Per Investigator's Assessment | The best overall response was defined as the participants with best response among complete response (CR) or partial response (PR) or stable disease (SD), or progressive disease (PD). It was assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than (<) 10 millimeter (mm). PR: at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters as the best overall response after randomization. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). | The response-evaluable population included all participants who received at least 1 dose of study drug in Part B, had measurable disease as entry criteria for Part B, and had at least 1 post-baseline disease assessment. | Posted | Count of Participants | Participants | Up to Cycle 11 (Cycle length =21 days) |
|
|
|
| 1 |
| 8 |
| 1 |
| 8 |
| 4 |
| 8 |
| EG001 | Part B: Pevonedistat + Paclitaxel and Carboplatin | Pevonedistat 20 mg/m^2, infusion, intravenously, single dose, on Days 1, 3 and 5 of each 21-days treatment cycle (up to 11 cycles), in combination with paclitaxel 175 mg/m^2, infusion, intravenously along with carboplatin AUC5, infusion, intravenously, on Day 1 of each 21-days treatment cycle (up to 11 cycles). Pevonedistat was administered after the paclitaxel and carboplatin chemotherapy. Participants who completed Part A and provided consent for Part B continued treatment in Part B. | 1 | 5 | 2 | 5 | 5 | 5 |
| EG002 | Part B: Pevonedistat + Docetaxel | Pevonedistat 25 mg/m^2, infusion, intravenously, single dose on Days 1, 3 and 5 of each 21-days treatment cycle (up to 11 cycles), in combination with docetaxel 75 mg/m^2, infusion, intravenously, on Day 1 of each 21-days treatment cycle (up to 11 cycles). Pevonedistat was administered after the docetaxel chemotherapy. Participants who completed Part A and provided consent for Part B continued treatment in Part B. | 1 | 2 | 1 | 2 | 2 | 2 |
| FIBROSARCOMA | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (21.0) | Systematic Assessment |
|
| PNEUMONIA | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| GENERAL PHYSICAL HEALTH DETERIORATION | General disorders | MedDRA (21.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Urinary Retention | Renal and urinary disorders | MedDRA (21.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Abdominal Distension | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (21.0) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (21.0) | Systematic Assessment |
|
| Oedema Peripheral | General disorders | MedDRA (21.0) | Systematic Assessment |
|
| Chest Pain | General disorders | MedDRA (21.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (21.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (21.0) | Systematic Assessment |
|
| Swelling | General disorders | MedDRA (21.0) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (21.0) | Systematic Assessment |
|
| Alanine Aminotransferase Increased | Investigations | MedDRA (21.0) | Systematic Assessment |
|
| Aspartate Aminotransferase Increased | Investigations | MedDRA (21.0) | Systematic Assessment |
|
| Blood Bilirubin Increased | Investigations | MedDRA (21.0) | Systematic Assessment |
|
| Platelet Count Decreased | Investigations | MedDRA (21.0) | Systematic Assessment |
|
| Blood Creatinine Increased | Investigations | MedDRA (21.0) | Systematic Assessment |
|
| Blood Urea Increased | Investigations | MedDRA (21.0) | Systematic Assessment |
|
| Weight Decreased | Investigations | MedDRA (21.0) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Oral Herpes | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
|
| Bone Pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
|
| Mueller's Mixed Tumour | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (21.0) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Systematic Assessment |
|
| Conjunctival Haemorrhage | Eye disorders | MedDRA (21.0) | Systematic Assessment |
|
| Spinal Compression Fracture | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Peripheral Venous Disease | Vascular disorders | MedDRA (21.0) | Systematic Assessment |
|
Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D056831 | Coordination Complexes |
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Metabolite-3 in Plasma |
|
| Metabolite-7 in Plasma |
|
| Metabolite-10b in Plasma |
|
| Metabolite-16 in Plasma |
|
| Metabolite-22 in Plasma |
|
| Pevonedistat in Urine |
|
| Metabolite-1 in Urine |
|
| Metabolite-2 in Urine |
|
| Metabolite-3 in Urine |
|
| Metabolite-7 in Urine |
|
| Metabolite-10b in Urine |
|
| Metabolite-16 in Urine |
|
| Metabolite-22 in Urine |
|
| Metabolite-23 in Urine |
|
| Metabolite-24 in Urine |
|
| Pevonedistat in Feces |
|
| Metabolite-1 in Feces |
|
| Metabolite-2 in Feces |
|
| Metabolite-3 in Feces |
|
| Metabolite-7 in Feces |
|
| SD |
|
| PD |
|