A Study of Adavosertib (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)

• ClinicalTrials.gov Identifier: NCT01357161
• Recruitment Status: Completed
• First Posted: May 20, 2011
• Results First Posted: September 7, 2017
• Last Update Posted: September 21, 2023
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Ovarian Cancer
• Interventions: Drug: adavosertib; Drug: Placebo; Drug: paclitaxel; Drug: carboplatin
• Enrollment: 136

Participant Flow

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
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.

Baseline Characteristics

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
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
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%

Outcome Measures

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
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

Outcome Measure Data

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
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)

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 (legacy)
	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)
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)

Outcome Measure Data

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
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)
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)

Outcome Measure Data

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
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

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 (legacy)
	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
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)

Outcome Measure Data

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
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

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 (legacy)
	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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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)

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 (legacy)
	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
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

Outcome Measure Data

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
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)

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 (legacy)
	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
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

Outcome Measure Data

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
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

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 (legacy)
	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]

Adverse Events

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
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	--/--		--/--		--/--
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
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

Limitations and Caveats

[Not Specified]

More Information

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

• Name/Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.
• Phone: 1-800-672-6372
• EMail: ClinicalTrialsDisclosure@merck.com

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT01357161
• 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: September 21, 2023