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A Dose-finding Study of MK-8628 in Participants With Recurrent Glioblastoma Multiforme (MK-8628-002)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02296476
Recruitment Status : Terminated (This study was terminated due to lack of clinical activity and not due to safety reasons.)
First Posted : November 20, 2014
Results First Posted : May 17, 2018
Last Update Posted : July 2, 2018
Sponsor:
Information provided by (Responsible Party):
Oncoethix GmbH

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Glioblastoma Multiforme
Intervention Drug: MK-8628
Enrollment 12
Recruitment Details 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.
Pre-assignment Details  
Arm/Group Title MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Hide Arm/Group Description 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. 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. 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.
Period Title: Overall Study
Started 6 4 2
Completed 0 0 0
Not Completed 6 4 2
Reason Not Completed
Disease Progression             6             4             2
Arm/Group Title MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg Total
Hide Arm/Group Description 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. 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 6 4 2 12
Hide Baseline Analysis Population Description
All participants who received at least one dose of study treatment
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 4 participants 2 participants 12 participants
49.7  (14.2) 55.8  (11.2) 54.5  (21.9) 52.5  (13.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 4 participants 2 participants 12 participants
Female
2
  33.3%
0
   0.0%
0
   0.0%
2
  16.7%
Male
4
  66.7%
4
 100.0%
2
 100.0%
10
  83.3%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants 0 participants
0
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
1.Primary Outcome
Title Progression-free Survival (PFS) at 6 Months
Hide Description 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.
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
2.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description 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.
Time Frame Up to 6 Months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 6 4 2
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
3.Secondary Outcome
Title Duration of Response (DOR)
Hide Description 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.
Time Frame Up to 6 Months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description 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.
Time Frame Up to 6 Months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Progression-free Survival
Hide Description 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.
Time Frame Up to 6 Months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 6 4 2
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
6.Secondary Outcome
Title Number of Participants Who Experienced at Least One Adverse Event (AE)
Hide Description 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.
Time Frame Up to 6 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study treatment.
Arm/Group Title MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 6 4 2
Measure Type: Count of Participants
Unit of Measure: Participants
6
 100.0%
4
 100.0%
2
 100.0%
7.Secondary Outcome
Title Number of Participants Who Experienced at Least One Toxicity Grade 3-5 AE
Hide Description 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.
Time Frame Up to 6 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study treatment.
Arm/Group Title MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 6 4 2
Measure Type: Count of Participants
Unit of Measure: Participants
3
  50.0%
1
  25.0%
2
 100.0%
8.Secondary Outcome
Title Number of Participants Who Discontinued Study Treatment Due to an AE
Hide Description The number of participants who discontinued study treatment due to an AE is presented.
Time Frame Up to 6 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study treatment.
Arm/Group Title MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 6 4 2
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
9.Secondary Outcome
Title Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1
Hide Description 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.
Time Frame Up to Cycle 1 (Up to 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 6 4 2
Measure Type: Count of Participants
Unit of Measure: Participants
1
  16.7%
0
   0.0%
2
 100.0%
10.Secondary Outcome
Title Observed Maximum Concentration (Cmax) of MK-8628
Hide Description 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.
Time Frame Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received MK-8628 and had blood samples drawn for PK analyses.
Arm/Group Title MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 6 4 2
Mean (Standard Deviation)
Unit of Measure: μg/Liter
1022  (377) 1138  (527) 2725 [1]   (NA)
[1]
Standard deviation could not be estimated for 2 participants.
11.Secondary Outcome
Title Time to Maximum Concentration (Tmax) of MK-8628
Hide Description 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.
Time Frame Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received MK-8628 and had blood samples drawn for PK analyses.
Arm/Group Title MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 6 4 2
Mean (Standard Deviation)
Unit of Measure: hours
1.7  (0.498) 2.50  (0.572) 2.04 [1]   (NA)
[1]
Standard deviation could not be estimated for 2 participants.
12.Secondary Outcome
Title Apparent Terminal Half-Life (t1/2) of MK-8628
Hide Description 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.
Time Frame Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received MK-8628 and had blood samples drawn for PK analyses.
Arm/Group Title MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 6 4 2
Mean (Standard Deviation)
Unit of Measure: hours
3.78  (0.366) 3.74  (0.431) 3.50 [1]   (NA)
[1]
Standard deviation could not be estimated for 2 participants.
13.Secondary Outcome
Title Apparent Total Body Clearance (Cl/F) of MK-8628
Hide Description 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.
Time Frame Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received MK-8628 and had blood samples drawn for PK analyses.
Arm/Group Title MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 6 4 2
Mean (Standard Deviation)
Unit of Measure: Liters/hour
10.4  (2.19) 13.0  (4.03) 7.75 [1]   (NA)
[1]
Standard deviation could not be estimated for 2 participants.
14.Secondary Outcome
Title Apparent Volume of Distribution During the Terminal Phase (Vz/F) of MK-8628
Hide Description 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.
Time Frame Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received MK-8628 and had blood samples drawn for PK analyses.
Arm/Group Title MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 6 4 2
Mean (Standard Deviation)
Unit of Measure: Liters
56.3  (9.73) 70.3  (24.1) 39.3 [1]   (NA)
[1]
Standard deviation could not be estimated for 2 participants.
15.Secondary Outcome
Title Observed Minimum Concentration (Cmin) of MK-8628
Hide Description 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.
Time Frame Predose on Days 29 and 57
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 1 3 0
Mean (Standard Deviation)
Unit of Measure: μg/Liter
85.4 [1]   (NA) 54.1  (35.4)
[1]
Not calculated on only 1 participant
16.Secondary Outcome
Title Area Under the Concentration-time Curve of MK-8628 From Time 0 to Infinity (AUC 0-∞)
Hide Description 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.
Time Frame Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received MK-8628 and had blood samples drawn for PK analyses.
Arm/Group Title MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 6 4 2
Mean (Standard Deviation)
Unit of Measure: μg•hours/Liter
8028  (2083) 10200  (4312) 20700 [1]   (NA)
[1]
Standard deviation could not be estimated for 2 participants.
Time Frame Up to 6 months (Day 1 through 28 of each treatment cycle for a maximum of 6 treatment cycles)
Adverse Event Reporting Description The Safety Population consisted of all participants who received at least one dose of study treatment.
 
Arm/Group Title MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Hide Arm/Group Description 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. 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. 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.
All-Cause Mortality
MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)      0/4 (0.00%)      0/2 (0.00%)    
Hide Serious Adverse Events
MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/6 (16.67%)      0/4 (0.00%)      2/2 (100.00%)    
Blood and lymphatic system disorders       
Thrombocytopenia  1  1/6 (16.67%)  1 0/4 (0.00%)  0 1/2 (50.00%)  1
Nervous system disorders       
Intracranial pressure increased  1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/2 (50.00%)  1
1
Term from vocabulary, MedDRA 18.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
MK-8628 80 mg MK-8628 120 mg MK-8628 160 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/6 (100.00%)      4/4 (100.00%)      2/2 (100.00%)    
Blood and lymphatic system disorders       
Thrombocytopenia  1  1/6 (16.67%)  1 1/4 (25.00%)  1 1/2 (50.00%)  1
Ear and labyrinth disorders       
Ear pain  1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Vertigo  1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Eye disorders       
Ocular icterus  1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/2 (50.00%)  1
Visual impairment  1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/2 (50.00%)  1
Gastrointestinal disorders       
Anal pruritus  1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Constipation  1  1/6 (16.67%)  1 0/4 (0.00%)  0 0/2 (0.00%)  0
Diarrhoea  1  2/6 (33.33%)  3 2/4 (50.00%)  3 2/2 (100.00%)  3
Dry mouth  1  1/6 (16.67%)  1 0/4 (0.00%)  0 0/2 (0.00%)  0
Dyspepsia  1  1/6 (16.67%)  1 0/4 (0.00%)  0 0/2 (0.00%)  0
Mouth haemorrhage  1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Nausea  1  2/6 (33.33%)  2 2/4 (50.00%)  2 0/2 (0.00%)  0
Vomiting  1  0/6 (0.00%)  0 1/4 (25.00%)  1 1/2 (50.00%)  1
General disorders       
Asthenia  1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Fatigue  1  4/6 (66.67%)  5 2/4 (50.00%)  2 1/2 (50.00%)  1
Infections and infestations       
Anal abscess  1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Candida infection  1  1/6 (16.67%)  1 0/4 (0.00%)  0 0/2 (0.00%)  0
Herpes zoster  1  1/6 (16.67%)  1 0/4 (0.00%)  0 0/2 (0.00%)  0
Investigations       
Blood bilirubin increased  1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/2 (50.00%)  3
Platelet count decreased  1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/2 (50.00%)  2
Weight decreased  1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Metabolism and nutrition disorders       
Hyperglycaemia  1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Hyperkalaemia  1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Hypokalaemia  1  1/6 (16.67%)  1 0/4 (0.00%)  0 1/2 (50.00%)  1
Musculoskeletal and connective tissue disorders       
Muscle spasms  1  1/6 (16.67%)  1 0/4 (0.00%)  0 0/2 (0.00%)  0
Myalgia  1  1/6 (16.67%)  2 0/4 (0.00%)  0 0/2 (0.00%)  0
Nervous system disorders       
Cognitive disorder  1  0/6 (0.00%)  0 1/4 (25.00%)  1 1/2 (50.00%)  1
Dysgeusia  1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Epilepsy  1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Headache  1  3/6 (50.00%)  4 2/4 (50.00%)  2 0/2 (0.00%)  0
Hemiparesis  1  1/6 (16.67%)  2 0/4 (0.00%)  0 0/2 (0.00%)  0
Intracranial pressure increased  1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/2 (50.00%)  2
Memory impairment  1  0/6 (0.00%)  0 1/4 (25.00%)  1 1/2 (50.00%)  1
Seizure  1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Psychiatric disorders       
Anxiety  1  1/6 (16.67%)  1 0/4 (0.00%)  0 0/2 (0.00%)  0
Insomnia  1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Renal and urinary disorders       
Acute kidney injury  1  0/6 (0.00%)  0 1/4 (25.00%)  2 0/2 (0.00%)  0
Proteinuria  1  1/6 (16.67%)  2 0/4 (0.00%)  0 0/2 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Cough  1  1/6 (16.67%)  1 0/4 (0.00%)  0 0/2 (0.00%)  0
Epistaxis  1  1/6 (16.67%)  1 0/4 (0.00%)  0 0/2 (0.00%)  0
Oropharyngeal pain  1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Skin and subcutaneous tissue disorders       
Dry skin  1  1/6 (16.67%)  1 0/4 (0.00%)  0 0/2 (0.00%)  0
Pruritus  1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Rash  1  2/6 (33.33%)  3 0/4 (0.00%)  0 0/2 (0.00%)  0
Rash maculo-papular  1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/2 (50.00%)  1
Vascular disorders       
Hypertension  1  1/6 (16.67%)  1 0/4 (0.00%)  0 0/2 (0.00%)  0
1
Term from vocabulary, MedDRA 18.1
Indicates events were collected by systematic assessment
This study was terminated 31-Aug-2015 because no clinical activity was detected. The study was not terminated due to safety reasons.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Oncoethix GmbH
ClinicalTrials.gov Identifier: NCT02296476    
Other Study ID Numbers: 8628-002
OTX015_107 ( Other Identifier: OncoEthix Protocol Number )
MK-8628-002 ( Other Identifier: Merck Protocol Number )
2014-001469-28 ( EudraCT Number )
First Submitted: October 3, 2014
First Posted: November 20, 2014
Results First Submitted: February 13, 2018
Results First Posted: May 17, 2018
Last Update Posted: July 2, 2018