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| ID | Type | Description | Link |
|---|---|---|---|
| OTX015_107 | Other Identifier | OncoEthix Protocol Number | |
| MK-8628-002 | Other Identifier | Merck Protocol Number | |
| 2014-001469-28 | EudraCT Number |
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This study was terminated due to lack of clinical activity and not due to safety reasons.
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A study of single-agent birabresib (MK-8628) (formerly known as OTX015) in recurrent GBM after standard front-line therapy failure.
The first phase of the study (dose escalation) will determine the maximum tolerated dose (MTD). MTD assessment will be based using dose-limiting toxicities (DLTs) observed during the first 28 days of treatment.
The second phase of the study (expansion cohort) will assess efficacy as measured by the progression-free survival rate at 6 months (PFS-6) as determined by an independent central review committee.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Birabresib 80 mg | Experimental | Participants received 80 mg of oral birabresib administered once daily (in a fasted state) every day in a 28-day cycle for up to 6 cycles. |
|
| Birabresib 120 mg | Experimental | Participants received 120 mg of oral birabresib administered once daily (in a fasted state) every day in a 28-day cycle for up to 6 cycles. |
|
| Birabresib 160 mg | Experimental | Participants received 160 mg of oral birabresib administered once daily (in a fasted state) every day in a 28-day cycle for up to 6 cycles. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Birabresib | Drug | Administered orally in a fasted state once daily. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival (PFS) at 6 Months | Progression-free survival was the time from the start of study treatment to the date of clinical or radiographic evidence of progressive disease according to Response Assessment in Neuro-Oncology (RANO) 2010 criteria or death. Progression, as assessed by RANO 2010, was defined as a ≥25% increase in sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration. PFS at 6 months was measured as the percentage of participants who were alive and progression-free at Month 6. PFS at 6 months was calculated for all participants who were actively enrolled in the study at the 6-month time point. | Month 6 |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) | ORR was defined as the number of participants in the analysis population who experienced a Complete Response (CR: complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks; no new lesions; no corticosteroids; and stable or improved clinically) or a Partial Response (PR: ≥50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks; no new lesions; stable or reduced corticosteroid dose; and stable or improved clinically) and was assessed using RANO 2010. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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Participants had a confirmed diagnosis of de novo glioblastoma multiforme (World Health Organization grade IV astrocytoma) with tumor recurrence following standard front-line treatment with surgery, cranial radiotherapy and temozolomide. Other inclusion and exclusion criteria applied.
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| ID | Title | Description |
|---|---|---|
| FG000 | MK-8628 80 mg | Participants received 80 mg of oral MK-8628 administered once daily (in a fasted state) every day in a 28-day cycle for up to 6 cycles. |
| FG001 | MK-8628 120 mg | Participants received 120 mg of oral MK-8628 administered once daily (in a fasted state) every day in a 28-day cycle for up to 6 cycles. |
| FG002 | MK-8628 160 mg | Participants received 160 mg of oral MK-8628 administered once daily (in a fasted state) every day in a 28-day cycle for up to 6 cycles. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All participants who received at least one dose of study treatment
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| ID | Title | Description |
|---|---|---|
| BG000 | MK-8628 80 mg | Participants received 80 mg of oral MK-8628 administered once daily (in a fasted state) every day in a 28-day cycle for up to 6 cycles. |
| BG001 | MK-8628 120 mg | Participants received 120 mg of oral MK-8628 administered once daily (in a fasted state) every day in a 28-day cycle for up to 6 cycles. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Progression-free Survival (PFS) at 6 Months | Progression-free survival was the time from the start of study treatment to the date of clinical or radiographic evidence of progressive disease according to Response Assessment in Neuro-Oncology (RANO) 2010 criteria or death. Progression, as assessed by RANO 2010, was defined as a ≥25% increase in sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration. PFS at 6 months was measured as the percentage of participants who were alive and progression-free at Month 6. PFS at 6 months was calculated for all participants who were actively enrolled in the study at the 6-month time point. | All participants who received at least 2 complete cycles (8 weeks) of treatment and had a baseline assessment and 1 on-study magnetic resonance imaging (MRI). Since no participants reached the 6-month time point in the study, PFS at 6 months could not be calculated. | Posted | Month 6 |
|
Up to 6 months (Day 1 through 28 of each treatment cycle for a maximum of 6 treatment cycles)
The Safety Population consisted of all participants who received at least one dose of study treatment.
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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 | MK-8628 80 mg | Participants received 80 mg of oral MK-8628 administered once daily (in a fasted state) every day in a 28-day cycle for up to 6 cycles. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 18.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 18.1 | Systematic Assessment |
This study was terminated 31-Aug-2015 because no clinical activity was detected. The study was not terminated due to safety reasons.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
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| ID | Term |
|---|---|
| C000605331 | OTX015 |
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| Up to 6 Months |
| Duration of Response (DOR) | DOR was the time from the first documented CR (complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks; no new lesions; no corticosteroids; and stable or improved clinically)or PR (≥50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks; no new lesions; stable or reduced corticosteroid dose; and stable or improved clinically), as assessed by RANO 2010, until documentation of disease progression, or the date of the last tumor assessment (if there was no documented progression), or the last tumor assessment before the start of further antitumor therapy. DOR was calculated for all participants who experienced a CR or PR. | Up to 6 Months |
| Overall Survival (OS) | OS was the time from the start of study treatment to the date of death. Participants were to be censored at their last contact if they were still alive at the cut-off date. OS was calculated for all participants who did not discontinue from the study due to disease progression. | Up to 6 Months |
| Progression-free Survival | Progression-free survival was the time from the start of study treatment to the date of clinical or radiographic evidence of progressive disease according to RANO 2010 criteria or death. Progression, as assessed by RANO 2010, was defined as a ≥25% increase in sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration. PFS was measured as the number of participants who were alive and progression-free for up to 6 months. | Up to 6 Months |
| Number of Participants Who Experienced at Least One Adverse Event (AE) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. The number of participants who experienced at least one AE is presented. | Up to 6 Months |
| Number of Participants Who Experienced at Least One Toxicity Grade 3-5 AE | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. The number of participants who experienced ≥1 Grade 3-5 AE per National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.03 criteria is presented. Grade 3 was classified as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care; Grade 4 was classified as potentially life-threatening or disabling; and Grade 5 was an AE resulting in death. | Up to 6 Months |
| Number of Participants Who Discontinued Study Treatment Due to an AE | The number of participants who discontinued study treatment due to an AE is presented. | Up to 6 Months |
| Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | A DLT was defined as any of the following toxicities that were considered by the investigator to be related to MK-8628: Hematologic toxicity: Grade 4 hematologic toxicity or febrile neutropenia, Grade 3 neutropenia with infection, Grade 3 thrombocytopenia with bleeding or lasting >7 days; Non-hematologic toxicity: Grade 3 or 4 non-hematologic toxicity (regardless of duration) unless it was not optimally managed with supportive care, Grade 3 or 4 laboratory abnormality lasting >7 days, or intolerable Grade 2 non-hematologic toxicity resulting in study treatment discontinuation or delay >7 days with or without dose reduction. | Up to Cycle 1 (Up to 28 days) |
| Observed Maximum Concentration (Cmax) of MK-8628 | Blood samples were obtained at specified time points for the pharmacokinetic (PK) analysis of Cmax of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry and Cmax was calculated using the nonlinear mixed-effects modelling software program Monolix version 4.3.2s. The Cmax of MK-8628 after oral administration is presented. | Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours postdose |
| Time to Maximum Concentration (Tmax) of MK-8628 | Blood samples were obtained at specified time points for the PK analysis of Tmax of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry and Tmax was calculated using the nonlinear mixed-effects modelling software program Monolix version 4.3.2s. The Tmax of MK-8628 after oral administration is presented. | Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours postdose |
| Apparent Terminal Half-Life (t1/2) of MK-8628 | Blood samples were obtained at specified time points for the PK analysis of t1/2 of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry and t1/2 was calculated using the nonlinear mixed-effects modelling software program Monolix version 4.3.2s. The t1/2 of MK-8628 after oral administration is presented. | Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours |
| Apparent Total Body Clearance (Cl/F) of MK-8628 | Blood samples were obtained at specified time points for the PK analysis of Cl/F of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry and Cl/F was calculated using the nonlinear mixed-effects modelling software program Monolix version 4.3.2s. The Cl/F of MK-8628 after oral administration is presented. | Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours |
| Apparent Volume of Distribution During the Terminal Phase (Vz/F) of MK-8628 | Blood samples were obtained at specified time points for the PK analysis of Vz/F of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry and Vz/F was calculated using the nonlinear mixed-effects modelling software program Monolix version 4.3.2s. The Vz/F of MK-8628 after oral administration is presented. | Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours |
| Observed Minimum Concentration (Cmin) of MK-8628 | Blood samples were obtained at specified time points for the PK analysis of Cmin of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry. A single Cmin value for MK-8628 was estimated using dose and steady-state predose concentrations of MK-8628 on Days 29 and 57. The Cmin of MK-8628 after oral administration is presented. | Predose on Days 29 and 57 |
| Area Under the Concentration-time Curve of MK-8628 From Time 0 to Infinity (AUC 0-∞) | Blood samples were obtained at specified time points for the PK analysis of AUC 0-∞ of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry. The AUC 0-∞ was estimated indirectly using the dose and CL/F values. The AUC 0-∞ of MK-8628 after oral administration is presented. | Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours |
| BG002 | MK-8628 160 mg | Participants received 160 mg of oral MK-8628 administered once daily (in a fasted state) every day in a 28-day cycle for up to 6 cycles. |
| BG003 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
Participants received 80 mg of oral MK-8628 administered once daily (in a fasted state) every day in a 28-day cycle for up to 6 cycles. |
| OG001 | MK-8628 120 mg | Participants received 120 mg of oral MK-8628 administered once daily (in a fasted state) every day in a 28-day cycle for up to 6 cycles. |
| OG002 | MK-8628 160 mg | Participants received 160 mg of oral MK-8628 administered once daily (in a fasted state) every day in a 28-day cycle for up to 6 cycles. |
|
| Secondary | Objective Response Rate (ORR) | ORR was defined as the number of participants in the analysis population who experienced a Complete Response (CR: complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks; no new lesions; no corticosteroids; and stable or improved clinically) or a Partial Response (PR: ≥50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks; no new lesions; stable or reduced corticosteroid dose; and stable or improved clinically) and was assessed using RANO 2010. | All participants who received at least 2 complete cycles (8 weeks) of treatment and had a baseline assessment and 1 on-study MRI or had discontinued early due to disease progression. | Posted | Count of Participants | Participants | Up to 6 Months |
|
|
|
| Secondary | Duration of Response (DOR) | DOR was the time from the first documented CR (complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks; no new lesions; no corticosteroids; and stable or improved clinically)or PR (≥50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks; no new lesions; stable or reduced corticosteroid dose; and stable or improved clinically), as assessed by RANO 2010, until documentation of disease progression, or the date of the last tumor assessment (if there was no documented progression), or the last tumor assessment before the start of further antitumor therapy. DOR was calculated for all participants who experienced a CR or PR. | All participants who received at least 2 complete cycles (8 weeks) of treatment and had a baseline assessment and 1 on-study MRI or had discontinued early due to disease progression. Since no participants experienced a CR or PR, DOR could not be calculated. | Posted | Up to 6 Months |
|
|
| Secondary | Overall Survival (OS) | OS was the time from the start of study treatment to the date of death. Participants were to be censored at their last contact if they were still alive at the cut-off date. OS was calculated for all participants who did not discontinue from the study due to disease progression. | All participants who received at least 2 complete cycles (8 weeks) of treatment and had a baseline assessment and 1 on-study MRI or had discontinued early due to disease progression. Since all participants discontinued the study due to disease progression, OS could not be calculated. | Posted | Up to 6 Months |
|
|
| Secondary | Progression-free Survival | Progression-free survival was the time from the start of study treatment to the date of clinical or radiographic evidence of progressive disease according to RANO 2010 criteria or death. Progression, as assessed by RANO 2010, was defined as a ≥25% increase in sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration. PFS was measured as the number of participants who were alive and progression-free for up to 6 months. | All participants who received at least 2 complete cycles (8 weeks) of treatment and had a baseline assessment and 1 on-study MRI or had discontinued early due to disease progression. | Posted | Count of Participants | Participants | Up to 6 Months |
|
|
|
| Secondary | Number of Participants Who Experienced at Least One Adverse Event (AE) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. The number of participants who experienced at least one AE is presented. | All participants who received at least one dose of study treatment. | Posted | Count of Participants | Participants | Up to 6 Months |
|
|
|
| Secondary | Number of Participants Who Experienced at Least One Toxicity Grade 3-5 AE | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. The number of participants who experienced ≥1 Grade 3-5 AE per National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.03 criteria is presented. Grade 3 was classified as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care; Grade 4 was classified as potentially life-threatening or disabling; and Grade 5 was an AE resulting in death. | All participants who received at least one dose of study treatment. | Posted | Count of Participants | Participants | Up to 6 Months |
|
|
|
| Secondary | Number of Participants Who Discontinued Study Treatment Due to an AE | The number of participants who discontinued study treatment due to an AE is presented. | All participants who received at least one dose of study treatment. | Posted | Count of Participants | Participants | Up to 6 Months |
|
|
|
| Secondary | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | A DLT was defined as any of the following toxicities that were considered by the investigator to be related to MK-8628: Hematologic toxicity: Grade 4 hematologic toxicity or febrile neutropenia, Grade 3 neutropenia with infection, Grade 3 thrombocytopenia with bleeding or lasting >7 days; Non-hematologic toxicity: Grade 3 or 4 non-hematologic toxicity (regardless of duration) unless it was not optimally managed with supportive care, Grade 3 or 4 laboratory abnormality lasting >7 days, or intolerable Grade 2 non-hematologic toxicity resulting in study treatment discontinuation or delay >7 days with or without dose reduction. | All participants who received at least 21 days of the planned dose of study drug during the first 28-day cycle or experienced a DLT. | Posted | Count of Participants | Participants | Up to Cycle 1 (Up to 28 days) |
|
|
|
| Secondary | Observed Maximum Concentration (Cmax) of MK-8628 | Blood samples were obtained at specified time points for the pharmacokinetic (PK) analysis of Cmax of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry and Cmax was calculated using the nonlinear mixed-effects modelling software program Monolix version 4.3.2s. The Cmax of MK-8628 after oral administration is presented. | All participants who received MK-8628 and had blood samples drawn for PK analyses. | Posted | Mean | Standard Deviation | μg/Liter | Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours postdose |
|
|
|
| Secondary | Time to Maximum Concentration (Tmax) of MK-8628 | Blood samples were obtained at specified time points for the PK analysis of Tmax of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry and Tmax was calculated using the nonlinear mixed-effects modelling software program Monolix version 4.3.2s. The Tmax of MK-8628 after oral administration is presented. | All participants who received MK-8628 and had blood samples drawn for PK analyses. | Posted | Mean | Standard Deviation | hours | Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours postdose |
|
|
|
| Secondary | Apparent Terminal Half-Life (t1/2) of MK-8628 | Blood samples were obtained at specified time points for the PK analysis of t1/2 of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry and t1/2 was calculated using the nonlinear mixed-effects modelling software program Monolix version 4.3.2s. The t1/2 of MK-8628 after oral administration is presented. | All participants who received MK-8628 and had blood samples drawn for PK analyses. | Posted | Mean | Standard Deviation | hours | Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours |
|
|
|
| Secondary | Apparent Total Body Clearance (Cl/F) of MK-8628 | Blood samples were obtained at specified time points for the PK analysis of Cl/F of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry and Cl/F was calculated using the nonlinear mixed-effects modelling software program Monolix version 4.3.2s. The Cl/F of MK-8628 after oral administration is presented. | All participants who received MK-8628 and had blood samples drawn for PK analyses. | Posted | Mean | Standard Deviation | Liters/hour | Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours |
|
|
|
| Secondary | Apparent Volume of Distribution During the Terminal Phase (Vz/F) of MK-8628 | Blood samples were obtained at specified time points for the PK analysis of Vz/F of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry and Vz/F was calculated using the nonlinear mixed-effects modelling software program Monolix version 4.3.2s. The Vz/F of MK-8628 after oral administration is presented. | All participants who received MK-8628 and had blood samples drawn for PK analyses. | Posted | Mean | Standard Deviation | Liters | Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours |
|
|
|
| Secondary | Observed Minimum Concentration (Cmin) of MK-8628 | Blood samples were obtained at specified time points for the PK analysis of Cmin of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry. A single Cmin value for MK-8628 was estimated using dose and steady-state predose concentrations of MK-8628 on Days 29 and 57. The Cmin of MK-8628 after oral administration is presented. | All participants who received MK-8628 and had predose blood samples drawn on Days 29 and 57 for steady state MK-8628 concentration. Participants in the 160 mg dose group were not analyzed for Cmin because they discontinued before Day 29. | Posted | Mean | Standard Deviation | μg/Liter | Predose on Days 29 and 57 |
|
|
|
| Secondary | Area Under the Concentration-time Curve of MK-8628 From Time 0 to Infinity (AUC 0-∞) | Blood samples were obtained at specified time points for the PK analysis of AUC 0-∞ of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry. The AUC 0-∞ was estimated indirectly using the dose and CL/F values. The AUC 0-∞ of MK-8628 after oral administration is presented. | All participants who received MK-8628 and had blood samples drawn for PK analyses. | Posted | Mean | Standard Deviation | μg•hours/Liter | Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours |
|
|
|
| 0 |
| 6 |
| 1 |
| 6 |
| 6 |
| 6 |
| EG001 | MK-8628 120 mg | Participants received 120 mg of oral MK-8628 administered once daily (in a fasted state) every day in a 28-day cycle for up to 6 cycles. | 0 | 4 | 0 | 4 | 4 | 4 |
| EG002 | MK-8628 160 mg | Participants received 160 mg of oral MK-8628 administered once daily (in a fasted state) every day in a 28-day cycle for up to 6 cycles. | 0 | 2 | 2 | 2 | 2 | 2 |
| Intracranial pressure increased | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA 18.1 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 18.1 | Systematic Assessment |
|
| Ocular icterus | Eye disorders | MedDRA 18.1 | Systematic Assessment |
|
| Visual impairment | Eye disorders | MedDRA 18.1 | Systematic Assessment |
|
| Anal pruritus | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Mouth haemorrhage | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Anal abscess | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Candida infection | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 18.1 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 18.1 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 18.1 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 18.1 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 18.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 18.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Cognitive disorder | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Epilepsy | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Hemiparesis | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Intracranial pressure increased | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Seizure | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 18.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 18.1 | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA 18.1 | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA 18.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 18.1 | Systematic Assessment |
|
The Sponsor has the opportunity to review proposed publications regarding this trial 45 days prior to submission for publication. Publication can be withheld an additional 90 days to allow for filing a patent or taking other measures to establish and preserve proprietary rights. Publication of the results of the study shall be made only as part of a publication of the results obtained by all sites performing the study.
| D009373 |
| Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| Male |
|