Trial Outcomes & Findings for A Long Term Safety Study of Suvorexant in Participants With Primary Insomnia (MK-4305-009 AM3) (NCT NCT01021813)
NCT ID: NCT01021813
Last Updated: 2018-09-21
Results Overview
Cataplexy is defined as a sudden loss of muscle tone while awake which prevents voluntary movement.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
781 participants
Primary outcome timeframe
From the first day of study treatment up to 12 months
Results posted on
2018-09-21
Participant Flow
Of the 781 participants randomized into the Treatment Phase, 522 were randomized to suvorexant and 259 were randomized to placebo. Two participants were randomized, but not treated (one from each treatment group); therefore, the total number of participants evaluated for safety was 779.
Participant milestones
| Measure |
Suvorexant
After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to \<65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the double-blind (DB) Treatment Phase.
|
Placebo
After a 1-week single-blind placebo run-in, participants received dose-matched placebo to suvorexant (administered according to age) daily before bedtime for 12 months during the DB Treatment Phase.
|
Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation)
Following treatment with suvorexant during the 12-Month DB Treatment Phase, participants received their same dose of suvorexant during a 2-month DB Randomized Discontinuation Phase.
|
Suvorexant (DB Treatment)/Placebo (DB Discontinuation)
Following treatment with suvorexant during the 12-Month DB Treatment Phase, participants received dose-matched placebo to suvorexant during a 2-month DB Randomized Discontinuation Phase.
|
Placebo (DB Treatment)/Placebo (DB Discontinuation)
Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Phase, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Randomized Discontinuation Phase.
|
|---|---|---|---|---|---|
|
DB Treatment Phase
STARTED
|
522
|
259
|
0
|
0
|
0
|
|
DB Treatment Phase
Treated
|
521
|
258
|
0
|
0
|
0
|
|
DB Treatment Phase
COMPLETED
|
322
|
162
|
0
|
0
|
0
|
|
DB Treatment Phase
NOT COMPLETED
|
200
|
97
|
0
|
0
|
0
|
|
DB Randomized Discontinuation Phase
STARTED
|
0
|
0
|
156
|
166
|
162
|
|
DB Randomized Discontinuation Phase
COMPLETED
|
0
|
0
|
152
|
161
|
157
|
|
DB Randomized Discontinuation Phase
NOT COMPLETED
|
0
|
0
|
4
|
5
|
5
|
Reasons for withdrawal
| Measure |
Suvorexant
After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to \<65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the double-blind (DB) Treatment Phase.
|
Placebo
After a 1-week single-blind placebo run-in, participants received dose-matched placebo to suvorexant (administered according to age) daily before bedtime for 12 months during the DB Treatment Phase.
|
Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation)
Following treatment with suvorexant during the 12-Month DB Treatment Phase, participants received their same dose of suvorexant during a 2-month DB Randomized Discontinuation Phase.
|
Suvorexant (DB Treatment)/Placebo (DB Discontinuation)
Following treatment with suvorexant during the 12-Month DB Treatment Phase, participants received dose-matched placebo to suvorexant during a 2-month DB Randomized Discontinuation Phase.
|
Placebo (DB Treatment)/Placebo (DB Discontinuation)
Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Phase, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Randomized Discontinuation Phase.
|
|---|---|---|---|---|---|
|
DB Treatment Phase
Adverse Event
|
60
|
22
|
0
|
0
|
0
|
|
DB Treatment Phase
Lack of Efficacy
|
44
|
28
|
0
|
0
|
0
|
|
DB Treatment Phase
Lost to Follow-up
|
14
|
12
|
0
|
0
|
0
|
|
DB Treatment Phase
Physician Decision
|
17
|
8
|
0
|
0
|
0
|
|
DB Treatment Phase
Pregnancy
|
1
|
0
|
0
|
0
|
0
|
|
DB Treatment Phase
Protocol Violation
|
4
|
3
|
0
|
0
|
0
|
|
DB Treatment Phase
Withdrawal by Subject
|
60
|
24
|
0
|
0
|
0
|
|
DB Randomized Discontinuation Phase
Adverse Event
|
0
|
0
|
0
|
3
|
1
|
|
DB Randomized Discontinuation Phase
Lack of Efficacy
|
0
|
0
|
0
|
1
|
0
|
|
DB Randomized Discontinuation Phase
Lost to Follow-up
|
0
|
0
|
0
|
0
|
1
|
|
DB Randomized Discontinuation Phase
Protocol Violation
|
0
|
0
|
1
|
0
|
0
|
|
DB Randomized Discontinuation Phase
Withdrawal by Subject
|
0
|
0
|
3
|
1
|
3
|
Baseline Characteristics
A Long Term Safety Study of Suvorexant in Participants With Primary Insomnia (MK-4305-009 AM3)
Baseline characteristics by cohort
| Measure |
Suvorexant
n=521 Participants
After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to \<65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the double-blind (DB) Treatment Phase.
|
Placebo
n=258 Participants
After a 1-week single-blind placebo run-in, participants received dose-matched placebo to suvorexant (administered according to age) daily before bedtime for 12 months during the DB Treatment Phase.
|
Total
n=779 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
61.3 years
STANDARD_DEVIATION 14.5 • n=5 Participants
|
62.0 years
STANDARD_DEVIATION 14.6 • n=7 Participants
|
61.5 years
STANDARD_DEVIATION 14.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
287 Participants
n=5 Participants
|
149 Participants
n=7 Participants
|
436 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
234 Participants
n=5 Participants
|
109 Participants
n=7 Participants
|
343 Participants
n=5 Participants
|
|
Mean Subjective Total Sleep Time (sTSTm)
|
320.4 minutes
STANDARD_DEVIATION 76.1 • n=5 Participants
|
329.9 minutes
STANDARD_DEVIATION 79.4 • n=7 Participants
|
323.5 minutes
STANDARD_DEVIATION 77.3 • n=5 Participants
|
|
Mean Subjective Time to Sleep Onset in minutes (sTSOm)
|
65.9 minutes
STANDARD_DEVIATION 63.8 • n=5 Participants
|
65.0 minutes
STANDARD_DEVIATION 60.6 • n=7 Participants
|
65.6 minutes
STANDARD_DEVIATION 62.7 • n=5 Participants
|
PRIMARY outcome
Timeframe: From the first day of study treatment up to 12 monthsPopulation: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
Cataplexy is defined as a sudden loss of muscle tone while awake which prevents voluntary movement.
Outcome measures
| Measure |
Suvorexant
n=521 Participants
After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to \<65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the double-blind (DB) Treatment Phase.
|
Placebo
n=258 Participants
After a 1-week single-blind placebo run-in, participants received dose-matched placebo to suvorexant (administered according to age) daily before bedtime for 12 months during the DB Treatment Phase.
|
Placebo (DB Treatment)/Placebo (DB Discontinuation)
Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Period, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Discontinuation Period.
|
|---|---|---|---|
|
Percentage of Participants Who Experienced Cataplexy Adverse Events (AEs) During the Double-Blind (DB) Treatment Phase
|
0.0 percentage of participants
|
0.0 percentage of participants
|
—
|
PRIMARY outcome
Timeframe: From the first day of study treatment up to 12 monthsPopulation: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment
Sleep paralysis was defined as the inability to perform voluntary muscle movements during sleep. Sleep paralysis adverse events included sleep-onset paralysis (paralysis as one is falling asleep).
Outcome measures
| Measure |
Suvorexant
n=521 Participants
After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to \<65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the double-blind (DB) Treatment Phase.
|
Placebo
n=258 Participants
After a 1-week single-blind placebo run-in, participants received dose-matched placebo to suvorexant (administered according to age) daily before bedtime for 12 months during the DB Treatment Phase.
|
Placebo (DB Treatment)/Placebo (DB Discontinuation)
Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Period, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Discontinuation Period.
|
|---|---|---|---|
|
Percentage of Participants Who Experienced Sleep Paralysis AEs During the DB Treatment Phase
|
0.4 percentage of participants
|
0.0 percentage of participants
|
—
|
PRIMARY outcome
Timeframe: From the first day of study treatment up to 12 monthsPopulation: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
Complex sleep-related behaviors were reported as ECIs and were characterized by patients engaging in specific activities while asleep (e.g., eating, drinking, preparing meals, making phone calls, having sex, driving, and sleep walking).
Outcome measures
| Measure |
Suvorexant
n=521 Participants
After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to \<65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the double-blind (DB) Treatment Phase.
|
Placebo
n=258 Participants
After a 1-week single-blind placebo run-in, participants received dose-matched placebo to suvorexant (administered according to age) daily before bedtime for 12 months during the DB Treatment Phase.
|
Placebo (DB Treatment)/Placebo (DB Discontinuation)
Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Period, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Discontinuation Period.
|
|---|---|---|---|
|
Percentage of Participants Who Experienced Complex Sleep-related Behaviors AEs During the DB Treatment Phase
any complex sleep-related behaviors
|
0.2 percentage of participants
|
0.0 percentage of participants
|
—
|
|
Percentage of Participants Who Experienced Complex Sleep-related Behaviors AEs During the DB Treatment Phase
somnambulism
|
0.2 percentage of participants
|
0.0 percentage of participants
|
—
|
PRIMARY outcome
Timeframe: From the first day of study treatment up to 12 monthsPopulation: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
Falls were adjudicated (to establish whether a fall event was due to cataplexy).
Outcome measures
| Measure |
Suvorexant
n=521 Participants
After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to \<65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the double-blind (DB) Treatment Phase.
|
Placebo
n=258 Participants
After a 1-week single-blind placebo run-in, participants received dose-matched placebo to suvorexant (administered according to age) daily before bedtime for 12 months during the DB Treatment Phase.
|
Placebo (DB Treatment)/Placebo (DB Discontinuation)
Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Period, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Discontinuation Period.
|
|---|---|---|---|
|
Percentage of Participants Who Experienced Falls AEs During the DB Treatment Phase
|
2.3 percentage of participants
|
3.1 percentage of participants
|
—
|
PRIMARY outcome
Timeframe: From the first day of study treatment up to 12 monthsPopulation: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
Suicidal ideation included suicidal plans, suicidal tendency, death wishes, life weariness, and suicidal intention. Suicidal behaviors included suicide attempts, suicide gesture, and self-injurious behaviour. Suicidal ideation and/or behavior was reported as an AE and considered an ECI.
Outcome measures
| Measure |
Suvorexant
n=521 Participants
After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to \<65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the double-blind (DB) Treatment Phase.
|
Placebo
n=258 Participants
After a 1-week single-blind placebo run-in, participants received dose-matched placebo to suvorexant (administered according to age) daily before bedtime for 12 months during the DB Treatment Phase.
|
Placebo (DB Treatment)/Placebo (DB Discontinuation)
Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Period, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Discontinuation Period.
|
|---|---|---|---|
|
Percentage of Participants Who Experienced Suicidal Ideation and/or Behavior AEs During the DB Treatment Phase
|
0.8 percentage of participants
|
0.0 percentage of participants
|
—
|
PRIMARY outcome
Timeframe: From the first day of study treatment up to 12 monthsPopulation: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
Perceptual distortions associated with transitions between wakefulness and sleep were termed as hypnagogic (occurring during the onset of sleep) or hypnopompic (occurring during onset of wakefulness) hallucinations.
Outcome measures
| Measure |
Suvorexant
n=521 Participants
After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to \<65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the double-blind (DB) Treatment Phase.
|
Placebo
n=258 Participants
After a 1-week single-blind placebo run-in, participants received dose-matched placebo to suvorexant (administered according to age) daily before bedtime for 12 months during the DB Treatment Phase.
|
Placebo (DB Treatment)/Placebo (DB Discontinuation)
Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Period, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Discontinuation Period.
|
|---|---|---|---|
|
Percentage of Participants Who Experienced Hypnagogic/Hypnopompic Hallucinations AEs During the DB Treatment Phase
Hypnopompic hallucination
|
0.2 percentage of participants
|
0.0 percentage of participants
|
—
|
|
Percentage of Participants Who Experienced Hypnagogic/Hypnopompic Hallucinations AEs During the DB Treatment Phase
Any hypnagogic/hypnopompic hallucinations AEs
|
0.8 percentage of participants
|
0.0 percentage of participants
|
—
|
|
Percentage of Participants Who Experienced Hypnagogic/Hypnopompic Hallucinations AEs During the DB Treatment Phase
Hypnagogic hallucination
|
0.6 percentage of participants
|
0.0 percentage of participants
|
—
|
PRIMARY outcome
Timeframe: From the first day of study treatment up to 12 monthsPopulation: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
The pre-specified terms which were suggestive of abuse potential on this study included depersonalization (feeling of watching oneself act, while having no control over a situation), derealization (alteration in the perception or experience of the external world so that it seems unreal), dissociation (includes a wide array of experiences from mild detachment from immediate surroundings to more severe detachment from physical and emotional experience), euphoric mood (exaggerated feeling of physical and emotional well-being and optimism not consonant with apparent stimuli or events), mania (state of abnormally elevated or irritable mood, arousal, and/or energy levels), hallucination (perception in the absence of a stimulus which has qualities of real perception), and potential study medication misuse.
Outcome measures
| Measure |
Suvorexant
n=521 Participants
After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to \<65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the double-blind (DB) Treatment Phase.
|
Placebo
n=258 Participants
After a 1-week single-blind placebo run-in, participants received dose-matched placebo to suvorexant (administered according to age) daily before bedtime for 12 months during the DB Treatment Phase.
|
Placebo (DB Treatment)/Placebo (DB Discontinuation)
Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Period, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Discontinuation Period.
|
|---|---|---|---|
|
Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase
any selected AE of potential abuse
|
3.5 percentage of participants
|
3.9 percentage of participants
|
—
|
|
Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase
Drug maladministration
|
2.3 percentage of participants
|
3.9 percentage of participants
|
—
|
|
Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase
Derealisation
|
0.2 percentage of participants
|
0.0 percentage of participants
|
—
|
|
Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase
Hallucination, auditory
|
0.2 percentage of participants
|
0.0 percentage of participants
|
—
|
|
Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase
Hallucination, visual
|
0.2 percentage of participants
|
0.0 percentage of participants
|
—
|
|
Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase
Hypnagogic hallucination
|
0.6 percentage of participants
|
0.0 percentage of participants
|
—
|
|
Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase
Hypnopompic hallucination
|
0.2 percentage of participants
|
0.0 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Evening of Month 12 visit and next 3 consecutive days (Night 1, 2, and 3 of Discontinuation Phase [otherwise known as the Run-out])Population: Participants in the APaT population who completed the entire DB Treatment Phase, had at least one measurement at the end of the DB Treatment Phase (Month 12), had taken at least one dose of Run-out study medication, and had a measurement on at least one of the nights of the DB Run-out Phase.
Withdrawal effects assessed using Tyrer WSQ, which evaluated the presence/absence and severity of withdrawal symptoms with 20 items (i.e. sensitivity to noise, light, smell, touch, feeling unreal, etc). The Tyrer WSQ was completed as part of the evening e-diary prior to dosing on the Month 12 visit and on the 3 consecutive evenings of the DB Run-out Phase (first 3 nights of DB Discontinuation Phase). Responses rated 0 (No), 1 (Yes-moderate), or 2 (Yes-severe); range from 0 (no withdrawal) to 40 (severe withdrawal). A participant was defined to have a withdrawal symptom if an item during any of the 3 DB Run-out days had emerged for the first time, or had worsened compared to the measurement obtained at the end of the Treatment phase (Month 12). For single night analysis, a patient was defined to have withdrawal effects if the number of withdrawal symptoms (emergent or worsening) was ≥3. For across night analysis, withdrawal was defined as a total of ≥3 symptoms across the 3 nights.
Outcome measures
| Measure |
Suvorexant
n=129 Participants
After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to \<65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the double-blind (DB) Treatment Phase.
|
Placebo
n=129 Participants
After a 1-week single-blind placebo run-in, participants received dose-matched placebo to suvorexant (administered according to age) daily before bedtime for 12 months during the DB Treatment Phase.
|
Placebo (DB Treatment)/Placebo (DB Discontinuation)
n=136 Participants
Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Period, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Discontinuation Period.
|
|---|---|---|---|
|
Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ)
Withdrawal Symptoms on Night 1 (n=121, 122, 131)
|
0.8 percentage of participants
|
1.6 percentage of participants
|
1.5 percentage of participants
|
|
Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ)
Withdrawal Symptoms on Night 2 (n=121, 124, 125)
|
0.8 percentage of participants
|
3.2 percentage of participants
|
2.4 percentage of participants
|
|
Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ)
Withdrawal Symptoms on Night 3 (n=116, 120, 128)
|
1.7 percentage of participants
|
2.5 percentage of participants
|
0.8 percentage of participants
|
|
Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ)
Symptoms Across Nights 1, 2, & 3 (n=129, 129, 136)
|
6.2 percentage of participants
|
6.2 percentage of participants
|
5.1 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline (Month 1) and first 3 days of Randomized Discontinuation Phase (otherwise known as the Run-out, Month 13)Population: Participants in the APaT population who completed the entire DB Treatment Phase, had a baseline measurement, had taken at least one dose of DB Run-out study medication, and had a measurement on at least one of the nights of the DB Run-out Phase.
Rebound insomnia was defined as insomnia that occurred following discontinuation of a sedative substance taken to relieve primary insomnia, and was assessed based on subjective total sleep time (sTST) as recorded in the participant's morning e-diary. A strict categorical analysis method (Yes/No) was used in which a participant was considered to have potentially experienced rebound (Yes) if the Morning Diary participant-reported sTST value (in minutes) on any of the 3 nights of the Run-out Phase (first 3 nights of the Discontinuation Phase) occurring after one year of treatment (Month 13) was less than the last value at baseline one year earlier (Month 1).
Outcome measures
| Measure |
Suvorexant
n=152 Participants
After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to \<65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the double-blind (DB) Treatment Phase.
|
Placebo
n=157 Participants
After a 1-week single-blind placebo run-in, participants received dose-matched placebo to suvorexant (administered according to age) daily before bedtime for 12 months during the DB Treatment Phase.
|
Placebo (DB Treatment)/Placebo (DB Discontinuation)
n=152 Participants
Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Period, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Discontinuation Period.
|
|---|---|---|---|
|
Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase
Rebound on Night 1 (n=137, 142, 139)
|
17.5 percentage of participants
|
33.8 percentage of participants
|
28.8 percentage of participants
|
|
Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase
Rebound on Night 2 (n=138, 146, 145)
|
19.6 percentage of participants
|
35.6 percentage of participants
|
26.9 percentage of participants
|
|
Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase
Rebound on Night 3 (n=131, 146, 139)
|
16.8 percentage of participants
|
37.7 percentage of participants
|
31.7 percentage of participants
|
|
Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase
Rebound on Nights 1, 2 or 3 (n=152, 157, 152)
|
28.9 percentage of participants
|
51.0 percentage of participants
|
40.1 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline (Month 1) and first 3 days of Randomized Discontinuation Phase (otherwise known as the Run-out, Month 13)Population: Participants in the APaT population who completed the entire DB Treatment Phase, had a baseline measurement, had taken at least one dose of DB Run-out study medication, and had a measurement on at least one of the nights of the DB Run-out Phase.
Rebound insomnia was defined as insomnia that occurred following discontinuation of a sedative substance taken to relieve primary insomnia, and was assessed based on subjective time to sleep onset (sTSO) as recorded in the participant's morning e-diary. A strict categorical analysis method (Yes/No) was used in which a participant was considered to have potentially experienced rebound (Yes) if the Morning Diary participant-reported sTSO value (in minutes) on any of the first 3 nights of the Run-out Phase occurring after one year of treatment (Month 13) was greater than the last value at baseline one year earlier (Month 1).
Outcome measures
| Measure |
Suvorexant
n=152 Participants
After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to \<65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the double-blind (DB) Treatment Phase.
|
Placebo
n=157 Participants
After a 1-week single-blind placebo run-in, participants received dose-matched placebo to suvorexant (administered according to age) daily before bedtime for 12 months during the DB Treatment Phase.
|
Placebo (DB Treatment)/Placebo (DB Discontinuation)
n=152 Participants
Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Period, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Discontinuation Period.
|
|---|---|---|---|
|
Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase
Rebound on Night 1 (n=137, 142, 139)
|
16.8 percentage of participants
|
26.8 percentage of participants
|
22.3 percentage of participants
|
|
Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase
Rebound on Night 2 (n=138, 146, 145)
|
18.8 percentage of participants
|
30.1 percentage of participants
|
24.8 percentage of participants
|
|
Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase
Rebound on Night 3 (n=131, 146, 139)
|
19.1 percentage of participants
|
30.1 percentage of participants
|
25.2 percentage of participants
|
|
Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase
Rebound on Nights 1, 2 or 3 (n=152, 157, 152)
|
31.6 percentage of participants
|
40.8 percentage of participants
|
36.2 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Week 1, Week 2, Week 3, and Week 4Population: Full Analysis Set (FAS)-Efficacy; all randomized participants who had ≥1 post-randomization observation for the analysis endpoint subsequent to ≥1 dose of study treatment, and baseline data for those analyses that required baseline data. The number included in the FAS may vary across endpoints due to the degree of missing data for each endpoint.
The sTSTm was defined as the average over time of daily e-diary values for a participant's report of the total amount of time spent asleep before waking for the day (measured in minutes). Weekly sTSTm values (Week 1, Week 2, etc.) were the average of the daily e-diary values for the week. A summary value of this measure for Month 1 was obtained by taking the average of weekly sTSTm values for Weeks 1 through 4; (Week 1 + Week 2 + Week 3 + Week 4) ÷ 4. LS Mean Change from Baseline in sTSTm was then calculated at Week 1, Week 2, Week 3, Week 4, and Month 1.
Outcome measures
| Measure |
Suvorexant
n=517 Participants
After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to \<65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the double-blind (DB) Treatment Phase.
|
Placebo
n=254 Participants
After a 1-week single-blind placebo run-in, participants received dose-matched placebo to suvorexant (administered according to age) daily before bedtime for 12 months during the DB Treatment Phase.
|
Placebo (DB Treatment)/Placebo (DB Discontinuation)
Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Period, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Discontinuation Period.
|
|---|---|---|---|
|
Least Squares (LS) Mean Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) During First Month of Treatment Phase
Change From BL at Week 1 (N=508, 252)
|
41.1 minutes
Interval 36.9 to 45.3
|
14.1 minutes
Interval 8.2 to 20.1
|
—
|
|
Least Squares (LS) Mean Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) During First Month of Treatment Phase
Change From BL at Week 2 (N=495, 248)
|
32.4 minutes
Interval 28.1 to 36.7
|
14.7 minutes
Interval 8.6 to 20.8
|
—
|
|
Least Squares (LS) Mean Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) During First Month of Treatment Phase
Change From BL at Week 3 (N=488, 241)
|
39.6 minutes
Interval 35.3 to 44.0
|
16.4 minutes
Interval 10.3 to 22.6
|
—
|
|
Least Squares (LS) Mean Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) During First Month of Treatment Phase
Change From BL at Week 4 (N=473, 238)
|
41.6 minutes
Interval 37.1 to 46.1
|
18.7 minutes
Interval 12.3 to 25.1
|
—
|
|
Least Squares (LS) Mean Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) During First Month of Treatment Phase
Change From BL at Month 1 Average (N=517, 254)
|
38.7 minutes
Interval 35.0 to 42.3
|
16.0 minutes
Interval 10.8 to 21.2
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 1, Week 2, Week 3, and Week 4Population: Full Analysis Set (FAS)-Efficacy; all randomized participants who had ≥1 post-randomization observation for the analysis endpoint subsequent to ≥1 dose of study treatment, and baseline data for those analyses that required baseline data. The number included in the FAS may vary across endpoints due to the degree of missing data for each endpoint.
The sTSOm was defined as the average over time of daily e-diary values for a participant's report of the time he or she required to fall asleep (measured in minutes). Weekly sTSOm values (Week 1, Week 2, etc.) were the average of the daily e-diary values for the week. A summary value of this measure for Month 1 was obtained by taking the average of weekly sTSTm values for Weeks 1 through 4; (Week 1 + Week 2 + Week 3 + Week 4) ÷ 4. LS Mean Change from Baseline in sTSOm was then calculated at Week 1, Week 2, Week 3, Week 4, and Month 1.
Outcome measures
| Measure |
Suvorexant
n=517 Participants
After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to \<65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the double-blind (DB) Treatment Phase.
|
Placebo
n=254 Participants
After a 1-week single-blind placebo run-in, participants received dose-matched placebo to suvorexant (administered according to age) daily before bedtime for 12 months during the DB Treatment Phase.
|
Placebo (DB Treatment)/Placebo (DB Discontinuation)
Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Period, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Discontinuation Period.
|
|---|---|---|---|
|
Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase
Change From BL at Week 4 (N=473, 238)
|
-19.9 minutes
Interval -23.1 to -16.6
|
-9.4 minutes
Interval -14.1 to -4.8
|
—
|
|
Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase
Change From BL at Week 1 (N=508, 252)
|
-17.7 minutes
Interval -20.9 to -14.5
|
-6.8 minutes
Interval -11.4 to -2.3
|
—
|
|
Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase
Change From BL at Week 2 (N=495, 248)
|
-15.7 minutes
Interval -19.2 to -12.2
|
-7.5 minutes
Interval -12.4 to -2.6
|
—
|
|
Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase
Change From BL at Week 3 (N=488, 241)
|
-18.7 minutes
Interval -22.2 to -15.2
|
-10.0 minutes
Interval -14.9 to -5.0
|
—
|
|
Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase
Change From BL at Month 1 Average (N=517, 254)
|
-18.0 minutes
Interval -20.9 to -15.1
|
-8.4 minutes
Interval -12.5 to -4.3
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From the first day of study treatment through study follow-up (up to 14 months)Population: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
Suicidal ideation and/or behavior that occurred on study was also assessed using the C-SSRS, a rater-administered questionnaire used to prospectively assess suicidal ideation and suicidal behavior. C-SSRS assessment was based upon a clinician's interpretation of the participant's responses to the C-SSRS questions, not by a numbered scale. Suicidal ideation and/or behaviors identified on the C-SSRS may not have been considered an adverse event, based on the investigator's judgment.
Outcome measures
| Measure |
Suvorexant
n=521 Participants
After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to \<65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the double-blind (DB) Treatment Phase.
|
Placebo
n=258 Participants
After a 1-week single-blind placebo run-in, participants received dose-matched placebo to suvorexant (administered according to age) daily before bedtime for 12 months during the DB Treatment Phase.
|
Placebo (DB Treatment)/Placebo (DB Discontinuation)
Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Period, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Discontinuation Period.
|
|---|---|---|---|
|
Number of Participants Who Reported Suicidal Ideation and/or Behavior On Study Based on Responses to the Columbia Suicide Severity Rating Scale (C-SSRS)
|
6 participants
|
0 participants
|
—
|
Adverse Events
Suvorexant
Serious events: 27 serious events
Other events: 184 other events
Deaths: 0 deaths
Placebo
Serious events: 17 serious events
Other events: 63 other events
Deaths: 0 deaths
Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation)
Serious events: 3 serious events
Other events: 7 other events
Deaths: 0 deaths
Suvorexant (DB Treatment)/Placebo (DB Discontinuation)
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Placebo (DB Treatment)/Placebo (DB Discontinuation)
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
Suvorexant (DB Treatment)/Suvorexant (DB Run-out)/Follow-up
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Suvorexant (DB Treatment)/Placebo (DB Run-out)/Follow-up
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Placebo (DB Treatment)/Placebo (DB Run-out)/Follow-up
Serious events: 2 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Suvorexant
n=521 participants at risk
After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to \<65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the double-blind (DB) Treatment Phase.
|
Placebo
n=258 participants at risk
After a 1-week single-blind placebo run-in, participants received dose-matched placebo to suvorexant (administered according to age) daily before bedtime for 12 months during the DB Treatment Phase.
|
Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation)
n=156 participants at risk
Following treatment with suvorexant during the 12-Month DB Treatment Phase, participants received their same dose of suvorexant during a 2-month DB Randomized Discontinuation Phase.
|
Suvorexant (DB Treatment)/Placebo (DB Discontinuation)
n=166 participants at risk
Following treatment with suvorexant during the 12-Month DB Treatment Phase, participants received dose-matched placebo to suvorexant during a 2-month DB Randomized Discontinuation Phase.
|
Placebo (DB Treatment)/Placebo (DB Discontinuation)
n=162 participants at risk
Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Phase, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Randomized Discontinuation Phase.
|
Suvorexant (DB Treatment)/Suvorexant (DB Run-out)/Follow-up
n=260 participants at risk
Following treatment with suvorexant during both the 12-Month DB Treatment Period and the DB Run-out period, participants entered a Follow-up Phase which concluded with a follow-up phone call 14 days after the last dose of study medication (or 14 days after the Discontinuation visit, whichever time point was later) to report AEs.
|
Suvorexant (DB Treatment)/Placebo (DB Run-out)/Follow-up
n=261 participants at risk
Following treatment with suvorexant during the 12-Month DB Treatment Period and treatment with dose-matched placebo during the DB the Run-out period, participants entered a Follow-up Phase which concluded with a follow-up phone call 14 days after the last dose of study medication (or 14 days after the Discontinuation visit, whichever time point was later) to report AEs.
|
Placebo (DB Treatment)/Placebo (DB Run-out)/Follow-up
n=258 participants at risk
Following treatment with dose-matched placebo during both the 12-Month DB Treatment Period and the DB Run-out period, participants entered a Follow-up Phase which concluded with a follow-up phone call 14 days after the last dose of study medication (or 14 days after the Discontinuation visit, whichever time point was later) to report AEs.
|
|---|---|---|---|---|---|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
1.2%
3/258 • Number of events 3 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Cardiac disorders
Coronary artery disease
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Ear and labyrinth disorders
Vertigo positional
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.64%
1/156 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/521 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.39%
1/258 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/521 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.39%
1/258 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Infections and infestations
Abdominal infection
|
0.00%
0/521 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.39%
1/258 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Infections and infestations
Cellulitis
|
0.00%
0/521 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.64%
1/156 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Infections and infestations
Diverticulitis
|
0.38%
2/521 • Number of events 2 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.39%
1/258 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Infections and infestations
Erysipelas
|
0.00%
0/521 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.39%
1/258 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Infections and infestations
Pneumonia
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Infections and infestations
Postoperative wound infection
|
0.00%
0/521 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.39%
1/258 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Infections and infestations
Urinary tract infection
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.39%
1/258 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Injury, poisoning and procedural complications
Concussion
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.00%
0/521 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.39%
1/258 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/521 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.39%
1/258 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Musculoskeletal and connective tissue disorders
Meniscal degeneration
|
0.00%
0/521 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.39%
1/258 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Musculoskeletal and connective tissue disorders
Spinal column stenosis
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Musculoskeletal and connective tissue disorders
Spondylitis
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.38%
2/521 • Number of events 2 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.78%
2/258 • Number of events 2 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.62%
1/162 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer in situ
|
0.00%
0/521 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.60%
1/166 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hodgkin's disease
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
0.00%
0/521 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.39%
1/258 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm skin
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.39%
1/258 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.64%
1/156 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine cancer
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/521 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.39%
1/258 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Nervous system disorders
Cervicobrachial syndrome
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Nervous system disorders
Headache
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Nervous system disorders
Migraine
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Nervous system disorders
Transient ischaemic attack
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.00%
0/521 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.38%
1/260 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Psychiatric disorders
Suicidal ideation
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Renal and urinary disorders
Calculus ureteric
|
0.00%
0/521 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.39%
1/258 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/521 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.39%
1/258 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Reproductive system and breast disorders
Vaginal prolapse
|
0.00%
0/521 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.39%
1/258 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Vascular disorders
Hypertension
|
0.00%
0/521 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.39%
1/258 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
General disorders
Non-cardiac chest pain
|
0.19%
1/521 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
Other adverse events
| Measure |
Suvorexant
n=521 participants at risk
After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to \<65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the double-blind (DB) Treatment Phase.
|
Placebo
n=258 participants at risk
After a 1-week single-blind placebo run-in, participants received dose-matched placebo to suvorexant (administered according to age) daily before bedtime for 12 months during the DB Treatment Phase.
|
Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation)
n=156 participants at risk
Following treatment with suvorexant during the 12-Month DB Treatment Phase, participants received their same dose of suvorexant during a 2-month DB Randomized Discontinuation Phase.
|
Suvorexant (DB Treatment)/Placebo (DB Discontinuation)
n=166 participants at risk
Following treatment with suvorexant during the 12-Month DB Treatment Phase, participants received dose-matched placebo to suvorexant during a 2-month DB Randomized Discontinuation Phase.
|
Placebo (DB Treatment)/Placebo (DB Discontinuation)
n=162 participants at risk
Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Phase, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Randomized Discontinuation Phase.
|
Suvorexant (DB Treatment)/Suvorexant (DB Run-out)/Follow-up
n=260 participants at risk
Following treatment with suvorexant during both the 12-Month DB Treatment Period and the DB Run-out period, participants entered a Follow-up Phase which concluded with a follow-up phone call 14 days after the last dose of study medication (or 14 days after the Discontinuation visit, whichever time point was later) to report AEs.
|
Suvorexant (DB Treatment)/Placebo (DB Run-out)/Follow-up
n=261 participants at risk
Following treatment with suvorexant during the 12-Month DB Treatment Period and treatment with dose-matched placebo during the DB the Run-out period, participants entered a Follow-up Phase which concluded with a follow-up phone call 14 days after the last dose of study medication (or 14 days after the Discontinuation visit, whichever time point was later) to report AEs.
|
Placebo (DB Treatment)/Placebo (DB Run-out)/Follow-up
n=258 participants at risk
Following treatment with dose-matched placebo during both the 12-Month DB Treatment Period and the DB Run-out period, participants entered a Follow-up Phase which concluded with a follow-up phone call 14 days after the last dose of study medication (or 14 days after the Discontinuation visit, whichever time point was later) to report AEs.
|
|---|---|---|---|---|---|---|---|---|
|
General disorders
Fatigue
|
6.5%
34/521 • Number of events 40 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
1.9%
5/258 • Number of events 5 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.62%
1/162 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Infections and infestations
Nasopharyngitis
|
8.1%
42/521 • Number of events 53 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
7.8%
20/258 • Number of events 25 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
3.2%
5/156 • Number of events 5 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
1.2%
2/166 • Number of events 2 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
2.5%
4/162 • Number of events 4 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.77%
2/260 • Number of events 2 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.39%
1/258 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Infections and infestations
Upper respiratory tract infection
|
5.4%
28/521 • Number of events 32 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
4.3%
11/258 • Number of events 13 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.64%
1/156 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
1.2%
2/166 • Number of events 3 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.62%
1/162 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Nervous system disorders
Dizziness
|
4.6%
24/521 • Number of events 29 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
6.2%
16/258 • Number of events 19 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.62%
1/162 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Nervous system disorders
Headache
|
8.3%
43/521 • Number of events 66 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
8.5%
22/258 • Number of events 25 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
1.3%
2/156 • Number of events 2 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/166 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
1.2%
2/162 • Number of events 2 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.38%
1/261 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/258 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
|
Nervous system disorders
Somnolence
|
13.2%
69/521 • Number of events 76 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
2.7%
7/258 • Number of events 7 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/156 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.60%
1/166 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/162 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/260 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.00%
0/261 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
0.39%
1/258 • Number of events 1 • AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
|
Additional Information
Vice President, Late Stage Development Group Leader
Merck Sharp & Dohme Corp
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER