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A Study of MK-1775 in Combination With Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone for Participants With Platinum-Sensitive Ovarian Tumors With the P53 Gene Mutation (MK-1775-004)

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ClinicalTrials.gov Identifier: NCT01357161
Recruitment Status : Completed
First Posted : May 20, 2011
Results First Posted : September 7, 2017
Last Update Posted : August 16, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Ovarian Cancer
Interventions Drug: MK-1775
Drug: Placebo
Drug: paclitaxel
Drug: carboplatin
Enrollment 136
Recruitment Details  
Pre-assignment Details Fifteen participants were enrolled in Part 1 and 121 participants were enrolled in Part 2 (n=136 total).
Arm/Group Title Part 1: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: Placebo + Paclitaxel +Carboplatin
Hide Arm/Group Description During the open-label run-in, participants received 225 mg MK-1775 twice daily (BID) starting on Day 1 of Cycle 1 (cycle=21 days) for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (area under the curve [AUC] 5). During Part 2, participants received 225 mg MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5). During Part 2, participants received matched placebo to MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received placebo in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5).
Period Title: Part 1 (Open Label Run-in)
Started 15 0 0
Completed 0 0 0
Not Completed 15 0 0
Reason Not Completed
Death             5             0             0
Lost to Follow-up             3             0             0
Physician Decision             1             0             0
Study Terminated By Sponsor             5             0             0
Withdrawal by Subject             1             0             0
Period Title: Part 2 (Double-Blind Comparison)
Started 0 59 [1] 62 [1]
Treated 0 59 60
Completed 0 0 0
Not Completed 0 59 62
Reason Not Completed
Death             0             22             19
Lost to Follow-up             0             1             6
Physician Decision             0             1             4
Progressive Disease             0             1             3
Study Terminated By Sponsor             0             29             26
Withdrawal by Subject             0             5             4
[1]
New participants enrolled in Part 2.
Arm/Group Title Part 1: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: Placebo + Paclitaxel +Carboplatin Total
Hide Arm/Group Description During the open-label run-in, participants received 225 mg MK-1775 twice daily (BID) starting on Day 1 of Cycle 1 (cycle=21 days) for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (area under the curve [AUC] 5). During Part 2, participants received 225 mg MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5). During Part 2, participants received matched placebo to MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received placebo in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5). Total of all reporting groups
Overall Number of Baseline Participants 15 59 62 136
Hide Baseline Analysis Population Description
All enrolled participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants 59 participants 62 participants 136 participants
58.2  (9.9) 58.3  (10.1) 60.4  (9.8) 59.3  (9.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 59 participants 62 participants 136 participants
Female
15
 100.0%
59
 100.0%
62
 100.0%
136
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Part 2: Median Progression-free Survival (PFS) in Weeks Based on Enhanced Response Evaluation Criteria In Solid Tumors Version 1.1 (Enhanced RECIST 1.1) by Independent Radiology Review
Hide Description PFS was defined as the time from randomization to progressive disease (based on blinded independent central radiologic review) or death, whichever occurred earlier. Tumor response was evaluated every 6 weeks during treatment by diagnostic anatomic imaging and objective response assessments were performed based on enhanced RECIST 1.1 criteria. According to enhanced RECIST 1.1, progressive disease was the appearance of one or more new lesions, OR an unambiguous increase in the sum of target lesion volumes with both 1) >20% increase in the sum of volumes (SOV) of all target lesions (taking as reference the nadir) and 2) greater than two times the variability of the measurements estimated by the sponsor and/or its designees. PFS was analyzed for Part 2 participants only using the Kaplan-Meier method and median PFS was reported in weeks. Per protocol, Part 1 participants were not included in this analysis.
Time Frame Up to 57 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population: All randomized participants in Part 2
Arm/Group Title Part 1: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: Placebo + Paclitaxel +Carboplatin
Hide Arm/Group Description:
During the open-label run-in, participants received 225 mg MK-1775 twice daily (BID) starting on Day 1 of Cycle 1 (cycle=21 days) for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (area under the curve [AUC] 5).
During Part 2, participants received 225 mg MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5).
During Part 2, participants received matched placebo to MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received placebo in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5).
Overall Number of Participants Analyzed 0 59 62
Median (95% Confidence Interval)
Unit of Measure: weeks
34.14
(29.86 to 43.14)
31.86
(24.43 to 35.57)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin, Part 2: Placebo + Paclitaxel +Carboplatin
Comments A stratified [number of prior platinum based regimens (1 vs. 2 and 3), time since last platinum based therapy (<12 months vs. ≥12 months)] Cox proportional hazards model, with Efron method of tie handling, was used to assess the magnitude of the treatment difference between the treatment arms. The p-value from the score test was used in the significance test and the hazard ratio (MK-1775 versus Placebo) and its 95% confidence interval from the same Cox model was reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.080
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.63
Confidence Interval (2-Sided) 80%
0.45 to 0.89
Estimation Comments [Not Specified]
2.Primary Outcome
Title Part 1: Number of Participants With a Dose Limiting Toxicity (DLT)
Hide Description DLTs assessed during first 21-day cycle of Part 1 and defined as toxicities that met pre-defined severity criteria, were possibly, probably, or definitely related to triplet therapy, and could possibly result in a change in the given dose. Hematologic DLTs included Grade (Gr) 3 or Gr 4 neutropenia with fever >38.5°C and/or infection requiring antibiotic or anti-fungal treatment, and any Gr 4-5 hematological toxicity EXCEPT Gr 4 anemia, leukopenia, lymphopenia, neutropenia lasting <7 days, and thrombocytopenia lasting <4 days, except if a platelet transfusion was required. Non-hematologic DLT defined as any Gr 3, 4, or 5 nonhematologic toxicity EXCEPT: Gr 3 nausea, vomiting, diarrhea, or dehydration judged by Investigator and SPONSOR to occur in setting of inadequate compliance with supportive care measures and last for less than 48 hours, alopecia of any grade, inadequately treated hypersensitivity reactions, or clinically non-significant, treatable or reversible lab abnormalities.
Time Frame During Cycle 1 of Part 1 (first 21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received ≥1 dose of study treatment during Cycle 1 of Part 1 open-label period and were evaluable at the time of the interim analysis. One participant took a prohibited medication during Part 1 and was considered unevaluable. Two participants enrolled into Part 1 after the interim analysis database lock and were not included.
Arm/Group Title Part 1: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: Placebo + Paclitaxel +Carboplatin
Hide Arm/Group Description:
During the open-label run-in, participants received 225 mg MK-1775 twice daily (BID) starting on Day 1 of Cycle 1 (cycle=21 days) for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (area under the curve [AUC] 5).
During Part 2, participants received 225 mg MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5).
During Part 2, participants received matched placebo to MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received placebo in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5).
Overall Number of Participants Analyzed 12 0 0
Measure Type: Number
Unit of Measure: participants
Total 3
Febrile neutropenia 1
Neutropenia 1
Thrombocytopenia 1
3.Primary Outcome
Title Parts 1 and 2: Percentage of Participants That Experienced an Adverse Event (AE)
Hide Description An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR’s products, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR’s product was also an AE. The percentage of participants that experienced at least one AE was reported for each treatment arm.
Time Frame Part 1: Day 1 through Post Study (286 days total). Part 2: Day 1 through Post Study (479 days total)
Hide Outcome Measure Data
Hide Analysis Population Description

Part 1: All participants who received at least one dose of study treatment during the open-label period.

Part 2: All randomized participants who received at least one dose of study treatment. 2 participants were randomized to the Part 2 placebo arm but were not treated.

Arm/Group Title Part 1: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: Placebo + Paclitaxel +Carboplatin
Hide Arm/Group Description:
During the open-label run-in, participants received 225 mg MK-1775 twice daily (BID) starting on Day 1 of Cycle 1 (cycle=21 days) for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (area under the curve [AUC] 5).
During Part 2, participants received 225 mg MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5).
During Part 2, participants received matched placebo to MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received placebo in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5).
Overall Number of Participants Analyzed 15 59 60
Measure Type: Number
Unit of Measure: percentage of participants
100.0 100.0 96.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin, Part 2: Placebo + Paclitaxel +Carboplatin
Comments P-values and 95% confidence intervals were calculated using the Miettinen and Nurminen method for between-treatment differences (MK-1775 vs. placebo) in the percentage of participants with events.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 3.3
Confidence Interval (2-Sided) 95%
-2.9 to 11.4
Estimation Comments [Not Specified]
4.Primary Outcome
Title Parts 1 and 2: Percentage of Participants That Discontinued Study Treatment Due to an AE
Hide Description An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR’s products, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR’s product was also an AE. The percentage of participants that discontinued study treatment (paclitaxel, carboplatin, or MK-1775) due to an AE was reported for each treatment arm.
Time Frame Part 1: Day 1 through Post Study (286 days total). Part 2: Day 1 through Post Study (479 days total)
Hide Outcome Measure Data
Hide Analysis Population Description

Part 1: All participants who received at least one dose of study treatment during the open-label period.

Part 2: All randomized participants who received at least one dose of study treatment. 2 participants were randomized to the Part 2 placebo arm but were not treated.

Arm/Group Title Part 1: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: Placebo + Paclitaxel +Carboplatin
Hide Arm/Group Description:
During the open-label run-in, participants received 225 mg MK-1775 twice daily (BID) starting on Day 1 of Cycle 1 (cycle=21 days) for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (area under the curve [AUC] 5).
During Part 2, participants received 225 mg MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5).
During Part 2, participants received matched placebo to MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received placebo in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5).
Overall Number of Participants Analyzed 15 59 60
Measure Type: Number
Unit of Measure: percentage of participants
20.0 20.3 21.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin, Part 2: Placebo + Paclitaxel +Carboplatin
Comments P-values and 95% confidence intervals were calculated using the Miettinen and Nurminen method for between-treatment differences (MK-1775 vs. placebo) in the percentage of participants with events.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-16.2 to 13.6
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Part 1: Objective Response Rate (ORR) Per Gynecological Cancer Intergroup (GCIG) Criteria Based on Both RECIST 1.1 and Cancer Antigen 125 (CA-125) Level by Independent Radiology Review
Hide Description ORR was defined as the percentage of participants whose best response was confirmed partial response (PR) or complete response (CR) based both on imaging per RECIST 1.1 and on serum marker CA-125 level according to GCIC criteria. CR was defined by RECIST 1.1 as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to <10 mm. PR was defined by RECIST 1.1 as at least a 30% decrease in the sum of the diameters (SOD) of target lesions, taking as reference the baseline SOD. A response according to CA-125 had occurred if there was ≥50% reduction in CA-125 levels from a pretreatment sample. The response must have been confirmed and maintained for at least 28 days. Participants could be evaluated according to CA-125 only if they had a pretreatment sample that was ≥2 times the upper limit of normal and within 2 weeks prior to starting treatment. Only evaluable Part 1 participants were included in this analysis.
Time Frame Up to 57 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants receiving MK-1775 (225 mg) during Part 1 and evaluable at the time of the interim analysis. One participant took a prohibited medication during Part 1 and was considered unevaluable. Two participants enrolled into Part 1 after the interim analysis database lock and were not included.
Arm/Group Title Part 1: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: Placebo + Paclitaxel +Carboplatin
Hide Arm/Group Description:
During the open-label run-in, participants received 225 mg MK-1775 twice daily (BID) starting on Day 1 of Cycle 1 (cycle=21 days) for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (area under the curve [AUC] 5).
During Part 2, participants received 225 mg MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5).
During Part 2, participants received matched placebo to MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received placebo in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5).
Overall Number of Participants Analyzed 12 0 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
75.00
(42.814 to 94.514)
6.Secondary Outcome
Title Part 2: Median PFS in Weeks Based on RECIST 1.1 by Independent Radiology Review
Hide Description PFS was defined as the time from randomization to progressive disease (based on blinded independent central radiologic review) or death, whichever occurred earlier. Tumor response was evaluated every 6 weeks during treatment by diagnostic anatomic imaging and objective response assessments were performed based on RECIST 1.1 criteria. According to RECIST 1.1, progressive disease was the appearance of one or more new lesions, OR a ≥20% increase in the sum of target lesion diameters (SOD) taking as reference the nadir (smallest SOD recorded since treatment started). PFS was analyzed for all randomized participants in Part 2 using the Kaplan-Meier method and median PFS was reported in weeks. Per protocol, Part 1 participants were not included in this analysis.
Time Frame Up to 57 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: All randomized participants in Part 2
Arm/Group Title Part 1: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: Placebo + Paclitaxel +Carboplatin
Hide Arm/Group Description:
During the open-label run-in, participants received 225 mg MK-1775 twice daily (BID) starting on Day 1 of Cycle 1 (cycle=21 days) for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (area under the curve [AUC] 5).
During Part 2, participants received 225 mg MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5).
During Part 2, participants received matched placebo to MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received placebo in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5).
Overall Number of Participants Analyzed 0 59 62
Median (95% Confidence Interval)
Unit of Measure: weeks
42.86
(35.00 to 48.86)
34.86
(30.43 to 36.86)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin, Part 2: Placebo + Paclitaxel +Carboplatin
Comments A stratified [number of prior platinum based regimens (1 vs. 2 and 3), time since last platinum based therapy (<12 months vs. ≥12 months)] Cox proportional hazards model, with Efron method of tie handling, was used to assess the magnitude of the treatment difference between the treatment arms. The p-value from the score test was used in the significance test and the hazard ratio (MK-1775 versus Placebo) and its 95% confidence interval from the same Cox model was reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.030
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.55
Confidence Interval (2-Sided) 80%
0.39 to 0.79
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Part 2: ORR Per GCIG Criteria Based on Both Enhanced RECIST 1.1 and CA125 Level by Independent Radiology Review
Hide Description ORR defined as the percentage of participants with best response of confirmed PR or CR based both on imaging per enhanced RECIST 1.1 and on serum marker CA-125 level according to GCIC criteria. CR defined by enhanced RECIST 1.1 as disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must have had reduction in short axis to <10 mm. PR was defined by enhanced RECIST 1.1 as ≥30% decrease in SOV of target lesions, taking as reference baseline SOV. Response according to CA-125 had occurred if there was ≥50% reduction in CA-125 levels from pretreatment sample. Response must have been confirmed and maintained for ≥28 days. Participants could be evaluated according to CA-125 only if they had a pretreatment sample that was ≥2 times the upper limit of normal and within 2 weeks prior to starting treatment. All randomized participants in Part 2 were analyzed. Per protocol, Part 1 participants were not included in this analysis.
Time Frame Up to 57 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: All randomized participants in Part 2
Arm/Group Title Part 1: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: Placebo + Paclitaxel +Carboplatin
Hide Arm/Group Description:
During the open-label run-in, participants received 225 mg MK-1775 twice daily (BID) starting on Day 1 of Cycle 1 (cycle=21 days) for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (area under the curve [AUC] 5).
During Part 2, participants received 225 mg MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5).
During Part 2, participants received matched placebo to MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received placebo in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5).
Overall Number of Participants Analyzed 0 59 62
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
74.58
(61.6 to 85.0)
69.35
(56.3 to 80.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin, Part 2: Placebo + Paclitaxel +Carboplatin
Comments Stratified Miettinen and Nurminen’s method with a two-sided p-Value for testing was used for comparison of the ORRs between the treatment groups in Part 2 portion of the study. A 95% confidence interval (CI) for the difference in response rates was provided.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5247
Comments [Not Specified]
Method Miettinen and Nurminen’s Method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rat
Estimated Value 5.2
Confidence Interval (2-Sided) 95%
-10.9 to 21.1
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Part 2: Median Overall Survival (OS) in Months
Hide Description OS was defined as the time from randomization to death due to any cause, reported in months. Participants without documented death at the time of analysis were censored at the date last known to be alive. For this endpoint, all randomized participants in Part 2 were analyzed. Per protocol, Part 1 participants were not evaluated for OS.
Time Frame Up to 57 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: All randomized participants in Part 2
Arm/Group Title Part 1: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: Placebo + Paclitaxel +Carboplatin
Hide Arm/Group Description:
During the open-label run-in, participants received 225 mg MK-1775 twice daily (BID) starting on Day 1 of Cycle 1 (cycle=21 days) for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (area under the curve [AUC] 5).
During Part 2, participants received 225 mg MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5).
During Part 2, participants received matched placebo to MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received placebo in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5).
Overall Number of Participants Analyzed 0 59 62
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(20.34 to NA)
NA [1] 
(NA to NA)
[1]
Median OS could not be calculated due to small percentage of death events observed by time of cut-off analysis date
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin, Part 2: Placebo + Paclitaxel +Carboplatin
Comments A stratified [number of prior platinum based regimens (1 vs. 2 and 3), time since last platinum based therapy (<12 months vs. ≥12 months)] Cox proportional hazards model, with Efron method of tie handling, was used to assess the magnitude of the treatment difference between the treatment arms. The p-value from the score test was used in the significance test and the hazard ratio (MK-1775 versus Placebo) and its 95% confidence interval from the same Cox model was reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.800
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.15
Confidence Interval (2-Sided) 95%
0.40 to 3.34
Estimation Comments [Not Specified]
Time Frame Part 1: Day 1 through Post Study (286 days total). Part 2: Day 1 through Post Study (479 days total)
Adverse Event Reporting Description

Part 1: All participants who received at least one dose of study treatment during the open-label period (n=15).

Part 2: All randomized participants who received at least one dose of study treatment (n=119). 2 participants were randomized to the Part 2 placebo arm but were not treated.

 
Arm/Group Title Part 1: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: Placebo + Paclitaxel +Carboplatin
Hide Arm/Group Description During the open-label run-in, participants received 225 mg MK-1775 twice daily (BID) starting on Day 1 of Cycle 1 (cycle=21 days) for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (area under the curve [AUC] 5). During Part 2, participants received 225 mg MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received MK-1775 in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5). During Part 2, participants received matched placebo to MK-1775 BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants received placebo in combination with paclitaxel (175 mg/m^2) and carboplatin (AUC 5).
All-Cause Mortality
Part 1: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: Placebo + Paclitaxel +Carboplatin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Part 1: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: Placebo + Paclitaxel +Carboplatin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/15 (60.00%)      24/59 (40.68%)      12/60 (20.00%)    
Blood and lymphatic system disorders       
Anaemia  1  0/15 (0.00%)  0 1/59 (1.69%)  1 0/60 (0.00%)  0
Febrile neutropenia  1  3/15 (20.00%)  3 13/59 (22.03%)  16 2/60 (3.33%)  2
Neutropenia  1  3/15 (20.00%)  3 2/59 (3.39%)  4 1/60 (1.67%)  1
Thrombocytopenia  1  1/15 (6.67%)  1 0/59 (0.00%)  0 1/60 (1.67%)  1
Cardiac disorders       
Sinus tachycardia  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Gastrointestinal disorders       
Abdominal pain  1  0/15 (0.00%)  0 0/59 (0.00%)  0 1/60 (1.67%)  1
Diarrhoea  1  2/15 (13.33%)  2 1/59 (1.69%)  1 1/60 (1.67%)  2
Ileus  1  0/15 (0.00%)  0 1/59 (1.69%)  1 0/60 (0.00%)  0
Intestinal obstruction  1  0/15 (0.00%)  0 1/59 (1.69%)  1 0/60 (0.00%)  0
Nausea  1  0/15 (0.00%)  0 0/59 (0.00%)  0 1/60 (1.67%)  1
Small intestinal obstruction  1  0/15 (0.00%)  0 1/59 (1.69%)  1 0/60 (0.00%)  0
Subileus  1  0/15 (0.00%)  0 1/59 (1.69%)  1 0/60 (0.00%)  0
Vomiting  1  1/15 (6.67%)  1 2/59 (3.39%)  2 1/60 (1.67%)  1
General disorders       
Adverse drug reaction  1  0/15 (0.00%)  0 0/59 (0.00%)  0 1/60 (1.67%)  1
Asthenia  1  0/15 (0.00%)  0 0/59 (0.00%)  0 1/60 (1.67%)  1
General physical health deterioration  1  0/15 (0.00%)  0 2/59 (3.39%)  3 0/60 (0.00%)  0
Influenza like illness  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Multi-organ failure  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Pyrexia  1  0/15 (0.00%)  0 1/59 (1.69%)  1 1/60 (1.67%)  1
Immune system disorders       
Drug hypersensitivity  1  0/15 (0.00%)  0 2/59 (3.39%)  2 2/60 (3.33%)  2
Infections and infestations       
Cellulitis  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Clostridium difficile infection  1  0/15 (0.00%)  0 1/59 (1.69%)  1 0/60 (0.00%)  0
Neutropenic sepsis  1  0/15 (0.00%)  0 1/59 (1.69%)  1 0/60 (0.00%)  0
Pneumonia  1  0/15 (0.00%)  0 1/59 (1.69%)  1 0/60 (0.00%)  0
Urinary tract infection  1  0/15 (0.00%)  0 1/59 (1.69%)  1 1/60 (1.67%)  1
Injury, poisoning and procedural complications       
Transfusion reaction  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Investigations       
Blood magnesium decreased  1  0/15 (0.00%)  0 1/59 (1.69%)  1 0/60 (0.00%)  0
Medical observation  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Platelet count decreased  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Metabolism and nutrition disorders       
Dehydration  1  0/15 (0.00%)  0 0/59 (0.00%)  0 1/60 (1.67%)  3
Hyperglycaemia  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Hyponatraemia  1  1/15 (6.67%)  1 1/59 (1.69%)  1 0/60 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Acute myeloid leukaemia  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Malignant neoplasm progression  1  0/15 (0.00%)  0 1/59 (1.69%)  1 0/60 (0.00%)  0
Nervous system disorders       
Loss of consciousness  1  0/15 (0.00%)  0 1/59 (1.69%)  1 0/60 (0.00%)  0
Syncope  1  0/15 (0.00%)  0 1/59 (1.69%)  1 1/60 (1.67%)  1
Psychiatric disorders       
Mental status changes  1  0/15 (0.00%)  0 1/59 (1.69%)  1 0/60 (0.00%)  0
Renal and urinary disorders       
Haematuria  1  0/15 (0.00%)  0 0/59 (0.00%)  0 1/60 (1.67%)  1
Renal failure acute  1  0/15 (0.00%)  0 0/59 (0.00%)  0 1/60 (1.67%)  3
Respiratory, thoracic and mediastinal disorders       
Cough  1  0/15 (0.00%)  0 1/59 (1.69%)  1 0/60 (0.00%)  0
Pulmonary embolism  1  1/15 (6.67%)  1 2/59 (3.39%)  2 0/60 (0.00%)  0
Skin and subcutaneous tissue disorders       
Acute febrile neutrophilic dermatosis  1  0/15 (0.00%)  0 0/59 (0.00%)  0 1/60 (1.67%)  1
Vascular disorders       
Hypotension  1  0/15 (0.00%)  0 1/59 (1.69%)  1 0/60 (0.00%)  0
Thrombosis  1  0/15 (0.00%)  0 1/59 (1.69%)  1 0/60 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin Part 2: Placebo + Paclitaxel +Carboplatin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/15 (100.00%)      59/59 (100.00%)      57/60 (95.00%)    
Blood and lymphatic system disorders       
Anaemia  1  6/15 (40.00%)  12 31/59 (52.54%)  68 19/60 (31.67%)  36
Leukopenia  1  2/15 (13.33%)  2 9/59 (15.25%)  25 12/60 (20.00%)  23
Lymph node pain  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Neutropenia  1  7/15 (46.67%)  16 24/59 (40.68%)  52 24/60 (40.00%)  58
Thrombocytopenia  1  3/15 (20.00%)  3 21/59 (35.59%)  64 16/60 (26.67%)  31
Cardiac disorders       
Palpitations  1  1/15 (6.67%)  1 3/59 (5.08%)  4 3/60 (5.00%)  3
Sinus tachycardia  1  1/15 (6.67%)  1 3/59 (5.08%)  3 2/60 (3.33%)  2
Tachycardia  1  1/15 (6.67%)  1 5/59 (8.47%)  5 2/60 (3.33%)  2
Ear and labyrinth disorders       
Ear pain  1  1/15 (6.67%)  1 5/59 (8.47%)  5 1/60 (1.67%)  1
Vertigo  1  1/15 (6.67%)  1 2/59 (3.39%)  5 2/60 (3.33%)  2
Eye disorders       
Diplopia  1  1/15 (6.67%)  2 0/59 (0.00%)  0 0/60 (0.00%)  0
Vision blurred  1  0/15 (0.00%)  0 4/59 (6.78%)  4 2/60 (3.33%)  3
Visual acuity reduced  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Gastrointestinal disorders       
Abdominal pain  1  3/15 (20.00%)  3 9/59 (15.25%)  11 14/60 (23.33%)  15
Abdominal pain upper  1  3/15 (20.00%)  3 4/59 (6.78%)  9 2/60 (3.33%)  4
Constipation  1  5/15 (33.33%)  5 17/59 (28.81%)  26 23/60 (38.33%)  29
Diarrhoea  1  13/15 (86.67%)  34 44/59 (74.58%)  138 22/60 (36.67%)  39
Dyspepsia  1  3/15 (20.00%)  5 6/59 (10.17%)  8 4/60 (6.67%)  5
Dysphagia  1  2/15 (13.33%)  2 1/59 (1.69%)  1 1/60 (1.67%)  1
Flatulence  1  1/15 (6.67%)  1 1/59 (1.69%)  1 0/60 (0.00%)  0
Gastric haemorrhage  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Gastrooesophageal reflux disease  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Haemorrhoids  1  3/15 (20.00%)  3 1/59 (1.69%)  2 1/60 (1.67%)  1
Nausea  1  13/15 (86.67%)  27 46/59 (77.97%)  103 36/60 (60.00%)  67
Odynophagia  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Oesophageal pain  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Oral dysaesthesia  1  1/15 (6.67%)  2 0/59 (0.00%)  0 0/60 (0.00%)  0
Proctalgia  1  1/15 (6.67%)  2 0/59 (0.00%)  0 2/60 (3.33%)  2
Rectal haemorrhage  1  1/15 (6.67%)  2 1/59 (1.69%)  2 0/60 (0.00%)  0
Stomatitis  1  1/15 (6.67%)  1 8/59 (13.56%)  9 6/60 (10.00%)  7
Vomiting  1  13/15 (86.67%)  33 37/59 (62.71%)  78 16/60 (26.67%)  19
General disorders       
Asthenia  1  2/15 (13.33%)  2 9/59 (15.25%)  16 2/60 (3.33%)  3
Chills  1  3/15 (20.00%)  5 3/59 (5.08%)  3 4/60 (6.67%)  7
Face oedema  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Fatigue  1  13/15 (86.67%)  17 32/59 (54.24%)  54 33/60 (55.00%)  37
Influenza like illness  1  0/15 (0.00%)  0 3/59 (5.08%)  3 1/60 (1.67%)  1
Injection site granuloma  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Localised oedema  1  1/15 (6.67%)  1 1/59 (1.69%)  1 1/60 (1.67%)  1
Malaise  1  3/15 (20.00%)  4 1/59 (1.69%)  1 4/60 (6.67%)  5
Mucosal inflammation  1  1/15 (6.67%)  1 3/59 (5.08%)  3 3/60 (5.00%)  3
Oedema peripheral  1  1/15 (6.67%)  3 9/59 (15.25%)  12 3/60 (5.00%)  3
Peripheral swelling  1  1/15 (6.67%)  1 3/59 (5.08%)  3 0/60 (0.00%)  0
Pyrexia  1  7/15 (46.67%)  8 6/59 (10.17%)  7 6/60 (10.00%)  6
Immune system disorders       
Drug hypersensitivity  1  2/15 (13.33%)  4 6/59 (10.17%)  16 6/60 (10.00%)  8
Hypersensitivity  1  1/15 (6.67%)  1 3/59 (5.08%)  4 4/60 (6.67%)  5
Infections and infestations       
Fungal skin infection  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Nasopharyngitis  1  2/15 (13.33%)  2 0/59 (0.00%)  0 3/60 (5.00%)  3
Oral herpes  1  1/15 (6.67%)  1 1/59 (1.69%)  1 1/60 (1.67%)  1
Pyelonephritis  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Rhinitis  1  0/15 (0.00%)  0 3/59 (5.08%)  3 1/60 (1.67%)  1
Upper respiratory tract infection  1  0/15 (0.00%)  0 3/59 (5.08%)  3 4/60 (6.67%)  4
Urinary tract infection  1  3/15 (20.00%)  6 7/59 (11.86%)  9 5/60 (8.33%)  7
Injury, poisoning and procedural complications       
Contusion  1  1/15 (6.67%)  1 2/59 (3.39%)  2 3/60 (5.00%)  3
Fall  1  1/15 (6.67%)  1 0/59 (0.00%)  0 1/60 (1.67%)  1
Spinal fracture  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Tooth fracture  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Investigations       
Alanine aminotransferase increased  1  3/15 (20.00%)  3 6/59 (10.17%)  6 3/60 (5.00%)  3
Aspartate aminotransferase increased  1  2/15 (13.33%)  2 4/59 (6.78%)  4 1/60 (1.67%)  1
Blood alkaline phosphatase increased  1  0/15 (0.00%)  0 3/59 (5.08%)  3 0/60 (0.00%)  0
Cardiac murmur  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Electrocardiogram QT prolonged  1  2/15 (13.33%)  2 0/59 (0.00%)  0 0/60 (0.00%)  0
Haemoglobin decreased  1  1/15 (6.67%)  1 1/59 (1.69%)  3 1/60 (1.67%)  2
Lymphocyte count decreased  1  0/15 (0.00%)  0 3/59 (5.08%)  6 0/60 (0.00%)  0
Neutrophil count decreased  1  2/15 (13.33%)  8 12/59 (20.34%)  30 9/60 (15.00%)  34
Platelet count decreased  1  5/15 (33.33%)  9 8/59 (13.56%)  23 6/60 (10.00%)  20
Weight decreased  1  1/15 (6.67%)  1 2/59 (3.39%)  2 1/60 (1.67%)  1
White blood cell count decreased  1  5/15 (33.33%)  9 7/59 (11.86%)  17 6/60 (10.00%)  15
Metabolism and nutrition disorders       
Decreased appetite  1  8/15 (53.33%)  10 11/59 (18.64%)  18 11/60 (18.33%)  17
Dehydration  1  5/15 (33.33%)  6 4/59 (6.78%)  10 3/60 (5.00%)  8
Glucose tolerance impaired  1  5/15 (33.33%)  15 0/59 (0.00%)  0 0/60 (0.00%)  0
Hypocalcaemia  1  2/15 (13.33%)  3 0/59 (0.00%)  0 1/60 (1.67%)  1
Hypokalaemia  1  3/15 (20.00%)  5 8/59 (13.56%)  12 0/60 (0.00%)  0
Hypomagnesaemia  1  6/15 (40.00%)  11 11/59 (18.64%)  16 9/60 (15.00%)  9
Hyponatraemia  1  2/15 (13.33%)  2 3/59 (5.08%)  3 1/60 (1.67%)  1
Musculoskeletal and connective tissue disorders       
Arthralgia  1  5/15 (33.33%)  11 15/59 (25.42%)  20 16/60 (26.67%)  23
Back pain  1  4/15 (26.67%)  5 5/59 (8.47%)  5 2/60 (3.33%)  2
Flank pain  1  0/15 (0.00%)  0 3/59 (5.08%)  3 0/60 (0.00%)  0
Musculoskeletal pain  1  1/15 (6.67%)  1 0/59 (0.00%)  0 1/60 (1.67%)  1
Myalgia  1  1/15 (6.67%)  1 15/59 (25.42%)  20 11/60 (18.33%)  17
Pain in extremity  1  1/15 (6.67%)  2 6/59 (10.17%)  8 5/60 (8.33%)  8
Nervous system disorders       
Dizziness  1  4/15 (26.67%)  4 8/59 (13.56%)  15 7/60 (11.67%)  11
Dysgeusia  1  6/15 (40.00%)  9 9/59 (15.25%)  11 7/60 (11.67%)  15
Headache  1  2/15 (13.33%)  3 10/59 (16.95%)  11 8/60 (13.33%)  11
Neuropathy peripheral  1  2/15 (13.33%)  2 8/59 (13.56%)  9 9/60 (15.00%)  11
Paraesthesia  1  0/15 (0.00%)  0 3/59 (5.08%)  3 7/60 (11.67%)  9
Peripheral sensory neuropathy  1  5/15 (33.33%)  9 12/59 (20.34%)  21 8/60 (13.33%)  9
Polyneuropathy  1  0/15 (0.00%)  0 6/59 (10.17%)  10 4/60 (6.67%)  5
Presyncope  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Restless legs syndrome  1  0/15 (0.00%)  0 3/59 (5.08%)  4 1/60 (1.67%)  1
Syncope  1  0/15 (0.00%)  0 4/59 (6.78%)  5 1/60 (1.67%)  1
Tremor  1  0/15 (0.00%)  0 3/59 (5.08%)  3 1/60 (1.67%)  1
Psychiatric disorders       
Agitation  1  1/15 (6.67%)  1 3/59 (5.08%)  3 2/60 (3.33%)  2
Anxiety  1  2/15 (13.33%)  2 2/59 (3.39%)  3 3/60 (5.00%)  4
Depression  1  3/15 (20.00%)  3 1/59 (1.69%)  1 1/60 (1.67%)  1
Insomnia  1  2/15 (13.33%)  3 10/59 (16.95%)  13 8/60 (13.33%)  8
Restlessness  1  0/15 (0.00%)  0 3/59 (5.08%)  3 1/60 (1.67%)  1
Renal and urinary disorders       
Dysuria  1  2/15 (13.33%)  3 2/59 (3.39%)  4 1/60 (1.67%)  1
Haematuria  1  1/15 (6.67%)  2 0/59 (0.00%)  0 2/60 (3.33%)  2
Pollakiuria  1  2/15 (13.33%)  2 2/59 (3.39%)  2 1/60 (1.67%)  1
Urinary incontinence  1  1/15 (6.67%)  2 0/59 (0.00%)  0 3/60 (5.00%)  3
Urinary tract pain  1  2/15 (13.33%)  3 1/59 (1.69%)  1 0/60 (0.00%)  0
Reproductive system and breast disorders       
Breast oedema  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Breast pain  1  1/15 (6.67%)  2 0/59 (0.00%)  0 0/60 (0.00%)  0
Pelvic pain  1  1/15 (6.67%)  2 1/59 (1.69%)  1 0/60 (0.00%)  0
Vaginal discharge  1  1/15 (6.67%)  1 1/59 (1.69%)  1 0/60 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Bronchospasm  1  1/15 (6.67%)  1 0/59 (0.00%)  0 1/60 (1.67%)  1
Cough  1  3/15 (20.00%)  4 8/59 (13.56%)  10 6/60 (10.00%)  10
Dysphonia  1  0/15 (0.00%)  0 3/59 (5.08%)  3 2/60 (3.33%)  2
Dyspnoea  1  4/15 (26.67%)  6 15/59 (25.42%)  23 8/60 (13.33%)  10
Epistaxis  1  0/15 (0.00%)  0 4/59 (6.78%)  4 4/60 (6.67%)  4
Oropharyngeal pain  1  2/15 (13.33%)  4 4/59 (6.78%)  4 4/60 (6.67%)  5
Skin and subcutaneous tissue disorders       
Alopecia  1  11/15 (73.33%)  11 32/59 (54.24%)  33 40/60 (66.67%)  40
Dermatitis  1  1/15 (6.67%)  1 0/59 (0.00%)  0 0/60 (0.00%)  0
Dermatitis acneiform  1  1/15 (6.67%)  1 0/59 (0.00%)  0 1/60 (1.67%)  1
Dermatitis allergic  1  2/15 (13.33%)  3 0/59 (0.00%)  0 0/60 (0.00%)  0
Hyperhidrosis  1  2/15 (13.33%)  2 1/59 (1.69%)  1 2/60 (3.33%)  3
Pruritus  1  3/15 (20.00%)  5 6/59 (10.17%)  6 7/60 (11.67%)  9
Rash  1  1/15 (6.67%)  2 2/59 (3.39%)  2 5/60 (8.33%)  5
Rash maculo-papular  1  3/15 (20.00%)  8 4/59 (6.78%)  7 4/60 (6.67%)  4
Skin lesion  1  1/15 (6.67%)  2 0/59 (0.00%)  0 0/60 (0.00%)  0
Vascular disorders       
Embolism  1  0/15 (0.00%)  0 3/59 (5.08%)  3 1/60 (1.67%)  1
Flushing  1  4/15 (26.67%)  5 1/59 (1.69%)  3 4/60 (6.67%)  7
Hypertension  1  5/15 (33.33%)  7 2/59 (3.39%)  2 3/60 (5.00%)  8
Hypotension  1  1/15 (6.67%)  1 1/59 (1.69%)  1 1/60 (1.67%)  1
Lymphoedema  1  0/15 (0.00%)  0 3/59 (5.08%)  3 0/60 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
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 must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission. SPONSOR review can be expedited to meet publication timelines.
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: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01357161     History of Changes
Other Study ID Numbers: 1775-004
2011-002803-13 ( EudraCT Number )
First Submitted: May 18, 2011
First Posted: May 20, 2011
Results First Submitted: August 8, 2017
Results First Posted: September 7, 2017
Last Update Posted: August 16, 2018