Trial Outcomes & Findings for Dose-Finding Safety and Efficacy Trial of Org50081 (Esmirtazapine) in the Treatment of Vasomotor Symptoms (46101/P06459/MK-8265-012) (NCT NCT00560833)

Last Updated: 2019-04-02

Results Overview

Participants recorded the frequency of vasomotor symptoms (hot flushes) on an electronic diary card (LogPad®) on a daily basis during screening and treatment. Frequency score A was based on the number of moderate hot flushes + the number of severe hot flushes in one day. Baseline average was derived from, at most, 7 completely observed pre-treatment days. Weekly averages during treatment were calculated if at least 4 days with non-missing data were completely observed; if less than 4 days were completely observed, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

943 participants

Primary outcome timeframe

Baseline and Week 4

Results posted on

2019-04-02

Participant Flow

942 participants were randomly assigned to treatment in this study, however, one screened participant was given placebo treatment without a randomization assignment. This participant is included in the study placebo population.

Participant milestones

Participant milestones
Measure	Placebo Participants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks	Esmirtazapine 2.25 mg Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 4.5 mg Participants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 9 mg Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 18mg Participants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks
Overall Study STARTED	317	155	160	155	156
Overall Study Treated	317	154	160	155	155
Overall Study COMPLETED	273	129	121	124	114
Overall Study NOT COMPLETED	44	26	39	31	42

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks	Esmirtazapine 2.25 mg Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 4.5 mg Participants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 9 mg Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 18mg Participants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks
Overall Study Adverse Event	16	10	25	23	35
Overall Study Lost to Follow-up	0	0	1	0	0
Overall Study Lack of Efficacy	22	9	6	4	4
Overall Study Participant uncooperative	5	5	4	4	2
Overall Study Other	1	1	3	0	0
Overall Study Never received drug	0	1	0	0	1

Baseline Characteristics

Dose-Finding Safety and Efficacy Trial of Org50081 (Esmirtazapine) in the Treatment of Vasomotor Symptoms (46101/P06459/MK-8265-012)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=317 Participants Participants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks	Esmirtazapine 2.25 mg n=154 Participants Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 4.5 mg n=160 Participants Participants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 9 mg n=155 Participants Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmertazapine 18 mg n=155 Participants Participants receive esmertazapine 18 mg, encapsulated tablet, PO, QD for up to 12 weeks	Total n=941 Participants Total of all reporting groups
Age, Continuous	54.0 Years STANDARD_DEVIATION 4.4 • n=5 Participants	53.4 Years STANDARD_DEVIATION 4.4 • n=7 Participants	54.1 Years STANDARD_DEVIATION 4.2 • n=5 Participants	54.9 Years STANDARD_DEVIATION 4.8 • n=4 Participants	54.1 Years STANDARD_DEVIATION 4.5 • n=21 Participants	54.1 Years STANDARD_DEVIATION 4.4 • n=8 Participants
Sex: Female, Male Female	317 Participants n=5 Participants	154 Participants n=7 Participants	160 Participants n=5 Participants	155 Participants n=4 Participants	155 Participants n=21 Participants	941 Participants n=8 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants

PRIMARY outcome

Timeframe: Baseline and Week 4

Population: The intent-to-treat (ITT) population, defined as all randomized particpants having at least one recorded pre-baseline value of the number of moderate and severe hot flushes.

Outcome measures

Outcome measures
Measure	Placebo n=294 Participants Participants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks	Esmirtazapine 2.25 mg n=138 Participants Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 4.5 mg n=139 Participants Participants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 9 mg n=137 Participants Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 18mg n=138 Participants Participants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks
Change From Baseline in Average Daily Frequency of Vasomotor Symptoms (Frequency Score A) at Week 4	-3.9 Number of events Standard Deviation 4.2	-5.6 Number of events Standard Deviation 3.8	-6.0 Number of events Standard Deviation 3.6	-6.0 Number of events Standard Deviation 4.0	-6.0 Number of events Standard Deviation 4.4

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: The ITT population, defined as all randomized particpants having at least one recorded pre-baseline value of the number of moderate and severe hot flushes.

Participants recorded the frequency of vasomotor symptoms (hot flushes) on a LogPad on a daily basis during screening and treatment. Frequency score A was based on the number of moderate hot flushes + the number of severe hot flushes in one day. Baseline average was derived from, at most, 7 completely observed pre-treatment days. Weekly averages during treatment were calculated if at least 4 days with non-missing data were completely observed; if less than 4 days were completely observed, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.

Outcome measures

Outcome measures
Measure	Placebo n=294 Participants Participants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks	Esmirtazapine 2.25 mg n=138 Participants Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 4.5 mg n=139 Participants Participants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 9 mg n=137 Participants Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 18mg n=138 Participants Participants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks
Change From Baseline in Average Daily Frequency of Vasomotor Symptoms (Frequency Score A) at Week 12	-4.9 number of events Standard Deviation 4.8	-6.2 number of events Standard Deviation 5.1	-6.7 number of events Standard Deviation 3.9	-6.9 number of events Standard Deviation 4.4	-6.5 number of events Standard Deviation 4.4

PRIMARY outcome

Timeframe: Baseline and Week 4

Population: The ITT population, defined as all randomized particpants having at least one recorded pre-baseline value of the number of moderate and severe hot flushes.

Participants recorded the severity of hot flushes on a LogPad on a daily basis during screening and treatment. The severity of hot flushes was defined as: mild (sensation of heat without sweating); moderate (sensation of heat with sweating, able to continue activity); and severe (sensation of heat with sweating, causing cessation of activity). Severity score A was calculated as the number of moderate hot flushes x 2 + the number of severe hot flushes x 3, divided by the total number of moderate and severe hot flushes. If no hot flushes were experienced, this was to be recorded as 'no sensation of heat'. Baseline values were based on, at most, 7 completely observed pre-treatment days. If less than 4 days were completely observed during treatment, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.

Outcome measures

Outcome measures
Measure	Placebo n=294 Participants Participants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks	Esmirtazapine 2.25 mg n=138 Participants Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 4.5 mg n=139 Participants Participants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 9 mg n=137 Participants Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 18mg n=138 Participants Participants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks
Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 4	-0.09 score on a scale Standard Deviation 0.23	-0.11 score on a scale Standard Deviation 0.22	-0.15 score on a scale Standard Deviation 0.25	-0.16 score on a scale Standard Deviation 0.24	-0.15 score on a scale Standard Deviation 0.24

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: The ITT population, defined as all randomized particpants having at least one recorded pre-baseline value of the number of moderate and severe hot flushes.

Outcome measures

Outcome measures
Measure	Placebo n=294 Participants Participants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks	Esmirtazapine 2.25 mg n=138 Participants Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 4.5 mg n=139 Participants Participants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 9 mg n=137 Participants Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 18mg n=138 Participants Participants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks
Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 12	-0.12 score on a scale Standard Deviation 0.28	-0.10 score on a scale Standard Deviation 0.27	-0.15 score on a scale Standard Deviation 0.29	-0.18 score on a scale Standard Deviation 0.26	-0.17 score on a scale Standard Deviation 0.26

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: All participants receiving study drug with diary compliance adequate for this measure.

The WHQ is a 36-item, user-friendly, and rapid way of assessing nine domains of physical and emotional health for mid-aged women. Participants self-administered the WHQ questionnaire; scoring is based on a 4-point scale as follows: 'Yes definitely=1', 'Yes sometimes=2', 'No not much=3' and 'No not at all=4'. Each score is transformed to a value '1' for scores '1' and '2' and to a value '0' for scores '3' and '4'. Vasomotor symptoms encompass Items 19 and 27 of the 36 total items. The transformed sums of items 19+27 are divided by 2 to get the score; therefore, the domain ranges from 0 to 1, where lower values are better.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Participants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks	Esmirtazapine 2.25 mg n=136 Participants Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 4.5 mg n=135 Participants Participants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 9 mg n=133 Participants Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 18mg n=136 Participants Participants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks
Change From Baseline in Vasomotor Symptoms Score Per Women's Health Questionnaire (WHQ) at Week 12 Baseline	0.984 Score on a scale Standard Deviation 0.088	0.993 Score on a scale Standard Deviation 0.060	0.985 Score on a scale Standard Deviation 0.085	0.981 Score on a scale Standard Deviation 0.114	0.985 Score on a scale Standard Deviation 0.085
Change From Baseline in Vasomotor Symptoms Score Per Women's Health Questionnaire (WHQ) at Week 12 Change from baseline	-0.151 Score on a scale Standard Deviation 0.329	-0.235 Score on a scale Standard Deviation 0.355	-0.256 Score on a scale Standard Deviation 0.355	-0.256 Score on a scale Standard Deviation 0.372	-0.246 Score on a scale Standard Deviation 0.385

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 128 other events

Deaths: 0 deaths

Esmirtazapine 2.25 mg

Serious events: 1 serious events

Other events: 93 other events

Deaths: 0 deaths

Esmirtazapine 4.5 mg

Serious events: 3 serious events

Other events: 99 other events

Deaths: 0 deaths

Esmirtazapine 9 mg

Serious events: 2 serious events

Other events: 102 other events

Deaths: 0 deaths

Esmirtazapine 18mg

Serious events: 0 serious events

Other events: 123 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=317 participants at risk Participants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks	Esmirtazapine 2.25 mg n=154 participants at risk Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 4.5 mg n=160 participants at risk Participants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 9 mg n=155 participants at risk Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 18mg n=155 participants at risk Participants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks
Gastrointestinal disorders Appendicitis perforated	0.00% 0/317 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.65% 1/154 • Number of events 1 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/160 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/155 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/155 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.
Gastrointestinal disorders Large intestine perforation	0.00% 0/317 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/154 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.62% 1/160 • Number of events 1 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/155 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/155 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.
General disorders Oedema peripheral	0.00% 0/317 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/154 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/160 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.65% 1/155 • Number of events 1 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/155 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.
Infections and infestations Pyelonephritis	0.32% 1/317 • Number of events 1 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/154 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/160 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/155 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/155 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/317 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/154 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.62% 1/160 • Number of events 1 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/155 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/155 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.
Psychiatric disorders Conversion disorder	0.00% 0/317 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/154 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.62% 1/160 • Number of events 1 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/155 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/155 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.
Reproductive system and breast disorders Vaginal lesion	0.00% 0/317 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/154 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/160 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.65% 1/155 • Number of events 1 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/155 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.
Skin and subcutaneous tissue disorders Scar	0.32% 1/317 • Number of events 1 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/154 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/160 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/155 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	0.00% 0/155 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.

Other adverse events

Other adverse events
Measure	Placebo n=317 participants at risk Participants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks	Esmirtazapine 2.25 mg n=154 participants at risk Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 4.5 mg n=160 participants at risk Participants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 9 mg n=155 participants at risk Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks	Esmirtazapine 18mg n=155 participants at risk Participants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks
Investigations Weight increased	5.7% 18/317 • Number of events 18 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	16.2% 25/154 • Number of events 25 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	15.0% 24/160 • Number of events 24 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	20.6% 32/155 • Number of events 33 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	29.0% 45/155 • Number of events 46 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.
Metabolism and nutrition disorders Increased appetite	4.1% 13/317 • Number of events 14 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	7.8% 12/154 • Number of events 12 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	13.1% 21/160 • Number of events 21 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	9.0% 14/155 • Number of events 16 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	18.1% 28/155 • Number of events 29 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	5.0% 16/317 • Number of events 17 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	3.2% 5/154 • Number of events 5 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	5.6% 9/160 • Number of events 10 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	9.0% 14/155 • Number of events 16 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	3.2% 5/155 • Number of events 5 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.
Gastrointestinal disorders Abdominal distension	2.5% 8/317 • Number of events 8 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	3.2% 5/154 • Number of events 5 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	5.0% 8/160 • Number of events 12 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	1.9% 3/155 • Number of events 4 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	5.8% 9/155 • Number of events 10 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.
Gastrointestinal disorders Dry mouth	1.9% 6/317 • Number of events 6 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	5.8% 9/154 • Number of events 9 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	4.4% 7/160 • Number of events 7 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	11.6% 18/155 • Number of events 21 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	14.2% 22/155 • Number of events 23 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.
Gastrointestinal disorders Nausea	5.4% 17/317 • Number of events 19 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	3.2% 5/154 • Number of events 5 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	3.1% 5/160 • Number of events 5 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	3.9% 6/155 • Number of events 7 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	3.2% 5/155 • Number of events 5 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.
General disorders Fatigue	3.5% 11/317 • Number of events 12 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	12.3% 19/154 • Number of events 24 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	11.9% 19/160 • Number of events 20 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	12.3% 19/155 • Number of events 22 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	12.9% 20/155 • Number of events 23 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.
General disorders Oedema peripheral	2.5% 8/317 • Number of events 10 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	5.8% 9/154 • Number of events 14 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	6.9% 11/160 • Number of events 11 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	4.5% 7/155 • Number of events 10 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	5.8% 9/155 • Number of events 9 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.
Infections and infestations Nasopharyngitis	4.7% 15/317 • Number of events 16 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	6.5% 10/154 • Number of events 10 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	6.9% 11/160 • Number of events 11 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	7.1% 11/155 • Number of events 12 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	6.5% 10/155 • Number of events 11 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.
Nervous system disorders Dizziness	3.8% 12/317 • Number of events 15 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	3.9% 6/154 • Number of events 10 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	7.5% 12/160 • Number of events 15 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	3.9% 6/155 • Number of events 7 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	9.0% 14/155 • Number of events 18 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.
Nervous system disorders Headache	17.0% 54/317 • Number of events 74 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	7.1% 11/154 • Number of events 11 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	8.1% 13/160 • Number of events 18 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	9.0% 14/155 • Number of events 16 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	12.3% 19/155 • Number of events 26 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.
Nervous system disorders Lethargy	0.32% 1/317 • Number of events 1 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	4.5% 7/154 • Number of events 7 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	8.8% 14/160 • Number of events 17 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	3.2% 5/155 • Number of events 6 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	2.6% 4/155 • Number of events 4 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.
Nervous system disorders Somnolence	6.0% 19/317 • Number of events 20 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	21.4% 33/154 • Number of events 43 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	23.1% 37/160 • Number of events 49 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	28.4% 44/155 • Number of events 54 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	32.3% 50/155 • Number of events 63 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.
Psychiatric disorders Insomnia	4.1% 13/317 • Number of events 18 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	3.9% 6/154 • Number of events 6 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	6.2% 10/160 • Number of events 10 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	3.9% 6/155 • Number of events 6 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.	8.4% 13/155 • Number of events 14 • Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60