Trial Outcomes & Findings for Safety and Efficacy Study of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder (NCT NCT01179516)

NCT ID: NCT01179516

Last Updated: 2013-12-18

Results Overview

The MADRS is a depression rating scale consisting of 10 items, each rated 0 (normal) to 6 (most abnormal). The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). A decrease in the total score or on individual items indicates improvement. Least squares (LS) means are from a mixed model for repeated measurements (MMRM) analysis of covariance (ANCOVA) with treatment, center, week, treatment-by-week interaction, Baseline MADRS total score-by-week as fixed effects.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 469 participants
• Primary outcome timeframe: Baseline and Week 8
• Results posted on: 2013-12-18

Participant Flow

Participants took part in the study at 65 investigative sites in the United States from 11 August 2010 to 04 June 2012.

Participants with a diagnosis of major depressive disorder were enrolled equally in 1 of 3 treatment groups, once a day placebo, 10 mg, or 15 mg vortioxetine.

Participant milestones

Measure	Placebo Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 15 mg Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Overall Study STARTED	160	157	152
Overall Study Treated	160	154	151
Overall Study COMPLETED	133	131	121
Overall Study NOT COMPLETED	27	26	31

Reasons for withdrawal

Measure	Placebo Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 15 mg Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Overall Study Pretreatment Event or Adverse Event	6	8	12
Overall Study Lack of Efficacy	4	2	0
Overall Study Noncompliance with Study Drug	2	0	1
Overall Study Protocol Deviations	4	3	3
Overall Study Withdrawal of Consent	2	6	10
Overall Study Lost to Follow-up	7	7	3
Overall Study Other	2	0	2

Baseline Characteristics

Safety and Efficacy Study of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder

Baseline characteristics by cohort

Measure	Placebo n=160 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg n=157 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 15 mg n=152 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks.	Total n=469 Participants Total of all reporting groups
Age Continuous	46.2 years STANDARD_DEVIATION 11.79 • n=5 Participants	45.2 years STANDARD_DEVIATION 11.94 • n=7 Participants	43.8 years STANDARD_DEVIATION 13.51 • n=5 Participants	45.1 years STANDARD_DEVIATION 12.44 • n=4 Participants
Age, Customized ≤55 years	122 participants n=5 Participants	129 participants n=7 Participants	120 participants n=5 Participants	371 participants n=4 Participants
Age, Customized >55 years	38 participants n=5 Participants	28 participants n=7 Participants	32 participants n=5 Participants	98 participants n=4 Participants
Sex: Female, Male Female	108 Participants n=5 Participants	113 Participants n=7 Participants	108 Participants n=5 Participants	329 Participants n=4 Participants
Sex: Female, Male Male	52 Participants n=5 Participants	44 Participants n=7 Participants	44 Participants n=5 Participants	140 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	20 participants n=5 Participants	16 participants n=7 Participants	18 participants n=5 Participants	54 participants n=4 Participants
Race/Ethnicity, Customized Non-Hispanic and non-Latino	140 participants n=5 Participants	141 participants n=7 Participants	134 participants n=5 Participants	415 participants n=4 Participants
Race/Ethnicity, Customized Caucasian (White, including Hispanic)	124 participants n=5 Participants	115 participants n=7 Participants	109 participants n=5 Participants	348 participants n=4 Participants
Race/Ethnicity, Customized Black	35 participants n=5 Participants	39 participants n=7 Participants	38 participants n=5 Participants	112 participants n=4 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants	6 participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Region of Enrollment United States	160 participants n=5 Participants	157 participants n=7 Participants	152 participants n=5 Participants	469 participants n=4 Participants
Height	168.85 cm STANDARD_DEVIATION 10.407 • n=5 Participants	167.35 cm STANDARD_DEVIATION 9.523 • n=7 Participants	167.52 cm STANDARD_DEVIATION 9.789 • n=5 Participants	167.92 cm STANDARD_DEVIATION 9.920 • n=4 Participants
Weight	89.14 kg STANDARD_DEVIATION 24.010 • n=5 Participants	87.74 kg STANDARD_DEVIATION 23.914 • n=7 Participants	86.49 kg STANDARD_DEVIATION 23.154 • n=5 Participants	87.81 kg STANDARD_DEVIATION 23.678 • n=4 Participants
Body Mass Index (BMI)	31.14 kg/m^2 STANDARD_DEVIATION 7.533 • n=5 Participants	31.29 kg/m^2 STANDARD_DEVIATION 8.063 • n=7 Participants	30.78 kg/m^2 STANDARD_DEVIATION 7.752 • n=5 Participants	31.07 kg/m^2 STANDARD_DEVIATION 7.771 • n=4 Participants
Waist Circumference	99.93 cm STANDARD_DEVIATION 17.820 • n=5 Participants	100.02 cm STANDARD_DEVIATION 16.762 • n=7 Participants	97.93 cm STANDARD_DEVIATION 17.536 • n=5 Participants	99.31 cm STANDARD_DEVIATION 17.370 • n=4 Participants
Smoking Classification Never smoked	83 participants n=5 Participants	86 participants n=7 Participants	62 participants n=5 Participants	231 participants n=4 Participants
Smoking Classification Current smoker	46 participants n=5 Participants	40 participants n=7 Participants	52 participants n=5 Participants	138 participants n=4 Participants
Smoking Classification Ex-smoker	31 participants n=5 Participants	31 participants n=7 Participants	38 participants n=5 Participants	100 participants n=4 Participants
Alcohol Consumption Never	49 participants n=5 Participants	54 participants n=7 Participants	51 participants n=5 Participants	154 participants n=4 Participants
Alcohol Consumption Once monthly or less often	60 participants n=5 Participants	56 participants n=7 Participants	62 participants n=5 Participants	178 participants n=4 Participants
Alcohol Consumption Once per week	26 participants n=5 Participants	20 participants n=7 Participants	21 participants n=5 Participants	67 participants n=4 Participants
Alcohol Consumption 2 to 6 times per week	24 participants n=5 Participants	22 participants n=7 Participants	14 participants n=5 Participants	60 participants n=4 Participants
Alcohol Consumption Daily	1 participants n=5 Participants	5 participants n=7 Participants	4 participants n=5 Participants	10 participants n=4 Participants
Montgomery Åsberg Depression Rating Scale (MADRS) Total Score	33.4 scores on a scale STANDARD_DEVIATION 4.53 • n=5 Participants	34.1 scores on a scale STANDARD_DEVIATION 4.07 • n=7 Participants	33.7 scores on a scale STANDARD_DEVIATION 4.51 • n=5 Participants	33.7 scores on a scale STANDARD_DEVIATION 4.37 • n=4 Participants
Hamilton Anxiety Scale Total Score	20.0 scores on a scale STANDARD_DEVIATION 6.14 • n=5 Participants	20.1 scores on a scale STANDARD_DEVIATION 5.77 • n=7 Participants	19.5 scores on a scale STANDARD_DEVIATION 5.42 • n=5 Participants	19.9 scores on a scale STANDARD_DEVIATION 5.78 • n=4 Participants
Clinical Global Impression - Severity scale score	4.7 sores on a scale STANDARD_DEVIATION 0.61 • n=5 Participants	4.7 sores on a scale STANDARD_DEVIATION 0.56 • n=7 Participants	4.6 sores on a scale STANDARD_DEVIATION 0.59 • n=5 Participants	4.7 sores on a scale STANDARD_DEVIATION 0.59 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full analysis set (FAS) included all randomized patients who received at least 1 dose of study drug, and had at least 1 valid post-baseline value for assessment of primary efficacy. A mixed model for repeated measurements (MMRM) based on observed cases was used.

The MADRS is a depression rating scale consisting of 10 items, each rated 0 (normal) to 6 (most abnormal). The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). A decrease in the total score or on individual items indicates improvement. Least squares (LS) means are from a mixed model for repeated measurements (MMRM) analysis of covariance (ANCOVA) with treatment, center, week, treatment-by-week interaction, Baseline MADRS total score-by-week as fixed effects.

Outcome measures

Measure	Placebo n=126 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg n=123 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 15 mg n=113 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score	-12.87 scores on a scale Standard Error 1.043	-13.66 scores on a scale Standard Error 1.064	-13.36 scores on a scale Standard Error 1.087

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set, last observation carried forward was used.

Response is defined as a participant with a ≥50% decrease in Montgomery Åsberg Depression Rating Scale (MADRS) total score from Baseline. The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.

Outcome measures

Measure	Placebo n=149 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg n=143 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 15 mg n=142 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Percentage of Participants With a MADRS Response at Week 8	32.9 percentage of participants	37.8 percentage of participants	37.3 percentage of participants

SECONDARY outcome

Timeframe: Week 8

Population: The Full Analysis Set. A mixed model for repeated measurements (MMRM) based on observed cases was used.

The Clinical Global Impression - global improvement assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. LS means were from a mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline Clinical Global Impression Scale-Severity of Illness (CGI-S) score-by-week as fixed effects.

Outcome measures

Measure	Placebo n=127 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg n=123 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 15 mg n=114 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Mean Clinical Global Impression Scale - Improvement (CGI-I) Score at Week 8	2.65 scores on a scale Standard Error 0.105	2.56 scores on a scale Standard Error 0.107	2.60 scores on a scale Standard Error 0.110

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set patients with a HAM-A Baseline score ≥ 20. A mixed model for repeated measurements (MMRM) based on observed cases was used.

The MADRS is a depression rating scale consisting of 10 items, each rated 0 (normal) to 6 (most abnormal). The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). A decrease in the total score or on individual items indicates improvement. LS means are from a mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline MADRS total score-by-week as fixed effects.

HAM-A is a 14 item rating scale to quantify anxiety severity rated on a 5-point scale from 0 (not present) to 4 (severe) with a total score range from 0 to 56, where lower scores indicate mild severity.

Outcome measures

Measure	Placebo n=60 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg n=57 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 15 mg n=56 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Change From Baseline in MADRS Total Score at Week 8 in Participants With Baseline Hamilton Anxiety Scale (HAM-A) Total Score ≥ 20	-14.11 scores on a scale Standard Error 1.611	-15.07 scores on a scale Standard Error 1.650	-12.37 scores on a scale Standard Error 1.689

SECONDARY outcome

Timeframe: Week 8

Population: Full analysis set, last observation carried forward was used.

Remission is defined as a participant with a Montgomery Åsberg Depression Rating Scale (MADRS) total score ≤10. The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.

Outcome measures

Measure	Placebo n=149 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg n=143 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 15 mg n=142 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Percentage of Participants in MADRS Remission at Week 8	22.1 percentage of participants	26.6 percentage of participants	23.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set. A mixed model for repeated measurements (MMRM) based on observed cases was used.

The Sheehan Disability Scale assesses functional impairment in 3 domains: work/school, social life or leisure activities, and home life or family responsibilities. The participant rates the extent to which each aspect is impaired on a 10-point visual analog scale, from 0 (not at all) to 10 (extremely). The 3 scores are added together to calculate the total score, which ranges from 0 to 30, with higher scores indicating more impairment. LS means were from mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline SDS total score-by-week as fixed effects.

Outcome measures

Measure	Placebo n=77 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg n=74 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 15 mg n=62 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Change From Baseline in Sheehan Disability Scale (SDS) Total Score	-9.38 scores on a scale Standard Error 0.877	-10.30 scores on a scale Standard Error 0.959	-8.69 scores on a scale Standard Error 0.990

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 92 other events

Deaths: 0 deaths

Vortioxetine 10 mg

Serious events: 1 serious events

Other events: 99 other events

Deaths: 0 deaths

Vortioxetine 15 mg

Serious events: 0 serious events

Other events: 96 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=160 participants at risk Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg n=154 participants at risk Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 15 mg n=151 participants at risk Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Nervous system disorders Lumbar radiculopathy	0.62% 1/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Suicidal ideation	0.00% 0/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.65% 1/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Measure	Placebo n=160 participants at risk Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg n=154 participants at risk Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 15 mg n=151 participants at risk Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Vascular disorders Hot flush	3.8% 6/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.66% 1/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders Vision blurred	0.62% 1/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.65% 1/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.6% 4/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Nausea	10.6% 17/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	30.5% 47/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.8% 51/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Dry mouth	6.9% 11/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	15.6% 24/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.3% 8/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Vomiting	2.5% 4/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.5% 7/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	11.9% 18/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Constipation	3.8% 6/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	10.4% 16/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	9.3% 14/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Diarrhoea	6.2% 10/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.5% 10/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	9.9% 15/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Flatulence	2.5% 4/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.5% 10/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.3% 5/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Dyspepsia	3.1% 5/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.9% 3/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.0% 3/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Fatigue	5.0% 8/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.2% 5/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.6% 4/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Irritability	3.1% 5/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 2/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 2/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Pain	2.5% 4/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.65% 1/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.66% 1/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Nasopharyngitis	5.0% 8/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.9% 6/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.0% 3/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Influenza	4.4% 7/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.9% 3/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.66% 1/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Viral upper respiratory tract infection	4.4% 7/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.2% 5/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.0% 3/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Upper respiratory tract infection	3.1% 5/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 2/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.0% 3/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Bronchitis	2.5% 4/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 2/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 2/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 6/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Myalgia	2.5% 4/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 2/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 2/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Headache	18.1% 29/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	15.6% 24/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.6% 25/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dizziness	9.4% 15/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.9% 6/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.9% 12/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Tension headache	1.9% 3/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.5% 7/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.0% 3/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Somnolence	1.2% 2/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.6% 4/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 6/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Insomnia	2.5% 4/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.6% 4/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 6/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Anxiety	0.62% 1/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.65% 1/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.6% 4/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.5% 4/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.6% 4/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Muscle strain	3.8% 6/160 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/154 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.66% 1/151 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director, Clinical Science

Takeda

Phone: 800-778-2860

Email: clinicaltrialregistry@tpna.com

Results disclosure agreements

• Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
• Publication restrictions are in place

Restriction type: OTHER