Trial Outcomes & Findings for Efficacy and Safety Study of Vortioxetine (Lu AA21004) for Treatment of Major Depressive Disorder (NCT NCT01255787)

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 were from an Analysis of Covariance (ANCOVA) model with treatment as a fixed factor and the Baseline value as a covariate.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

600 participants

Primary outcome timeframe

Baseline and Week 8

Results posted on

2013-12-18

Participant Flow

Participants took part in the study at 90 investigative sites in Japan, Europe and Asia/Oceania from 18 November 2010 to 25 April 2012.

Participants with a diagnosis of major depressive disorder were enrolled equally in 1 of 4 treatment groups, once a day placebo, 5 mg, 10 mg, or 20 mg vortioxetine.

Participant milestones

Participant milestones
Measure	Placebo Vortioxetine placebo-matching tablets, orally, once daily for up to 10 weeks.	Vortioxetine 5 mg Vortioxetine 5 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.	Vortioxetine 10 mg Vortioxetine 10 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.	Vortioxetine 20 mg Vortioxetine 10 mg, tablets, orally, once daily for 1 week, followed by vortioxetine 20 mg, tablets, orally, once daily for 7 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily, for 2 weeks.
Overall Study STARTED	152	144	150	154
Overall Study Treated	152	144	148	150
Overall Study COMPLETED	136	127	132	132
Overall Study NOT COMPLETED	16	17	18	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Vortioxetine placebo-matching tablets, orally, once daily for up to 10 weeks.	Vortioxetine 5 mg Vortioxetine 5 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.	Vortioxetine 10 mg Vortioxetine 10 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.	Vortioxetine 20 mg Vortioxetine 10 mg, tablets, orally, once daily for 1 week, followed by vortioxetine 20 mg, tablets, orally, once daily for 7 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily, for 2 weeks.
Overall Study Pretreatment Event or Adverse Event (AE)	6	2	9	9
Overall Study Major Protocol Deviation	1	1	0	4
Overall Study Lost to Follow-up	1	2	4	2
Overall Study Withdrawal of Consent	3	9	3	4
Overall Study Pregnancy	0	0	0	1
Overall Study Lack of Efficacy	2	2	2	2
Overall Study Noncompliance with Study Drug	3	1	0	0

Baseline Characteristics

Efficacy and Safety Study of Vortioxetine (Lu AA21004) for Treatment of Major Depressive Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=152 Participants Vortioxetine placebo-matching tablets, orally, once daily for up to 10 weeks.	Vortioxetine 5 mg n=144 Participants Vortioxetine 5 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.	Vortioxetine 10 mg n=150 Participants Vortioxetine 10 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.	Vortioxetine 20 mg n=154 Participants Vortioxetine 10 mg, tablets, orally, once daily for 1 week, followed by vortioxetine 20 mg, tablets, orally, once daily for 7 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily, for 2 weeks.	Total n=600 Participants Total of all reporting groups
Age Continuous	43.6 years STANDARD_DEVIATION 11.57 • n=5 Participants	44.2 years STANDARD_DEVIATION 11.89 • n=7 Participants	45.7 years STANDARD_DEVIATION 10.90 • n=5 Participants	44.0 years STANDARD_DEVIATION 11.79 • n=4 Participants	44.4 years STANDARD_DEVIATION 11.54 • n=21 Participants
Sex: Female, Male Female	91 Participants n=5 Participants	98 Participants n=7 Participants	93 Participants n=5 Participants	93 Participants n=4 Participants	375 Participants n=21 Participants
Sex: Female, Male Male	61 Participants n=5 Participants	46 Participants n=7 Participants	57 Participants n=5 Participants	61 Participants n=4 Participants	225 Participants n=21 Participants
Race/Ethnicity, Customized Caucasian (or White, including Hispanic)	104 participants n=5 Participants	101 participants n=7 Participants	104 participants n=5 Participants	105 participants n=4 Participants	414 participants n=21 Participants
Race/Ethnicity, Customized Asian	48 participants n=5 Participants	43 participants n=7 Participants	46 participants n=5 Participants	49 participants n=4 Participants	186 participants n=21 Participants
Region of Enrollment Croatia	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants	3 participants n=21 Participants
Region of Enrollment Finland	5 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants	5 participants n=4 Participants	20 participants n=21 Participants
Region of Enrollment Germany	50 participants n=5 Participants	50 participants n=7 Participants	50 participants n=5 Participants	49 participants n=4 Participants	199 participants n=21 Participants
Region of Enrollment India	3 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	2 participants n=4 Participants	11 participants n=21 Participants
Region of Enrollment Japan	33 participants n=5 Participants	32 participants n=7 Participants	31 participants n=5 Participants	33 participants n=4 Participants	129 participants n=21 Participants
Region of Enrollment Latvia	3 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	3 participants n=4 Participants	10 participants n=21 Participants
Region of Enrollment Malaysia	2 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants	4 participants n=21 Participants
Region of Enrollment Philippines	4 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants	3 participants n=4 Participants	13 participants n=21 Participants
Region of Enrollment Poland	20 participants n=5 Participants	18 participants n=7 Participants	20 participants n=5 Participants	21 participants n=4 Participants	79 participants n=21 Participants
Region of Enrollment Romania	5 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants	3 participants n=4 Participants	18 participants n=21 Participants
Region of Enrollment Russia	13 participants n=5 Participants	13 participants n=7 Participants	12 participants n=5 Participants	13 participants n=4 Participants	51 participants n=21 Participants
Region of Enrollment Serbia	2 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants	2 participants n=4 Participants	9 participants n=21 Participants
Region of Enrollment South Korea	6 participants n=5 Participants	6 participants n=7 Participants	7 participants n=5 Participants	8 participants n=4 Participants	27 participants n=21 Participants
Region of Enrollment Ukraine	6 participants n=5 Participants	6 participants n=7 Participants	7 participants n=5 Participants	8 participants n=4 Participants	27 participants n=21 Participants
Height	167.1 cm STANDARD_DEVIATION 8.75 • n=5 Participants	167.2 cm STANDARD_DEVIATION 9.64 • n=7 Participants	167.5 cm STANDARD_DEVIATION 9.40 • n=5 Participants	167.5 cm STANDARD_DEVIATION 9.61 • n=4 Participants	167.3 cm STANDARD_DEVIATION 9.33 • n=21 Participants
Weight	69.70 kg STANDARD_DEVIATION 16.901 • n=5 Participants	70.57 kg STANDARD_DEVIATION 18.214 • n=7 Participants	73.37 kg STANDARD_DEVIATION 19.014 • n=5 Participants	70.21 kg STANDARD_DEVIATION 18.189 • n=4 Participants	70.95 kg STANDARD_DEVIATION 18.095 • n=21 Participants
Body Mass Index (BMI)	24.82 kg/m^2 STANDARD_DEVIATION 5.129 • n=5 Participants	25.06 kg/m^2 STANDARD_DEVIATION 5.432 • n=7 Participants	25.93 kg/m^2 STANDARD_DEVIATION 5.462 • n=5 Participants	24.82 kg/m^2 STANDARD_DEVIATION 5.206 • n=4 Participants	25.15 kg/m^2 STANDARD_DEVIATION 5.313 • n=21 Participants
Smoking Classification Current smoker	51 participants n=5 Participants	50 participants n=7 Participants	50 participants n=5 Participants	56 participants n=4 Participants	207 participants n=21 Participants
Smoking Classification Ex-smoker	22 participants n=5 Participants	19 participants n=7 Participants	21 participants n=5 Participants	11 participants n=4 Participants	73 participants n=21 Participants
Smoking Classification Never smoked	79 participants n=5 Participants	75 participants n=7 Participants	79 participants n=5 Participants	87 participants n=4 Participants	320 participants n=21 Participants
History of Alcohol Consumption Never	58 participants n=5 Participants	62 participants n=7 Participants	54 participants n=5 Participants	56 participants n=4 Participants	230 participants n=21 Participants
History of Alcohol Consumption Once monthly or less often	52 participants n=5 Participants	41 participants n=7 Participants	54 participants n=5 Participants	53 participants n=4 Participants	200 participants n=21 Participants
History of Alcohol Consumption Once a week	17 participants n=5 Participants	22 participants n=7 Participants	22 participants n=5 Participants	22 participants n=4 Participants	83 participants n=21 Participants
History of Alcohol Consumption 2 to 6 times per week	14 participants n=5 Participants	9 participants n=7 Participants	10 participants n=5 Participants	13 participants n=4 Participants	46 participants n=21 Participants
History of Alcohol Consumption Daily	11 participants n=5 Participants	10 participants n=7 Participants	10 participants n=5 Participants	10 participants n=4 Participants	41 participants n=21 Participants
Status of Major Depressive Episode (MDE) Single episode	51 participants n=5 Participants	55 participants n=7 Participants	49 participants n=5 Participants	49 participants n=4 Participants	204 participants n=21 Participants
Status of Major Depressive Episode (MDE) Recurrent episode	101 participants n=5 Participants	89 participants n=7 Participants	101 participants n=5 Participants	105 participants n=4 Participants	396 participants n=21 Participants
Pharmacotherapy for Current Major Depressive Episode Yes	73 participants n=5 Participants	60 participants n=7 Participants	69 participants n=5 Participants	75 participants n=4 Participants	277 participants n=21 Participants
Pharmacotherapy for Current Major Depressive Episode No	79 participants n=5 Participants	84 participants n=7 Participants	81 participants n=5 Participants	79 participants n=4 Participants	323 participants n=21 Participants
Montgomery Åsberg Depression Rating Scale (MADRS) Total Score	31.6 scores on a scale STANDARD_DEVIATION 3.56 • n=5 Participants	31.6 scores on a scale STANDARD_DEVIATION 3.67 • n=7 Participants	31.8 scores on a scale STANDARD_DEVIATION 4.02 • n=5 Participants	31.7 scores on a scale STANDARD_DEVIATION 3.73 • n=4 Participants	31.7 scores on a scale STANDARD_DEVIATION 3.74 • n=21 Participants
Clinical Global Impression - Severity scale score	4.7 scores on a scale STANDARD_DEVIATION 0.66 • n=5 Participants	4.7 scores on a scale STANDARD_DEVIATION 0.65 • n=7 Participants	4.7 scores on a scale STANDARD_DEVIATION 0.66 • n=5 Participants	4.7 scores on a scale STANDARD_DEVIATION 0.65 • n=4 Participants	4.70 scores on a scale STANDARD_DEVIATION 0.65 • n=21 Participants
Sheehan Disability Scale (SDS) - Total score	18.2 scores on a scale STANDARD_DEVIATION 5.28 • n=5 Participants	17.9 scores on a scale STANDARD_DEVIATION 6.27 • n=7 Participants	18.5 scores on a scale STANDARD_DEVIATION 5.42 • n=5 Participants	18.2 scores on a scale STANDARD_DEVIATION 5.70 • n=4 Participants	18.2 scores on a scale STANDARD_DEVIATION 5.65 • n=21 Participants
Hamilton Anxiety Scale Total Score	18.6 scores on a scale STANDARD_DEVIATION 6.83 • n=5 Participants	18.9 scores on a scale STANDARD_DEVIATION 6.55 • n=7 Participants	18.8 scores on a scale STANDARD_DEVIATION 6.66 • n=5 Participants	18.5 scores on a scale STANDARD_DEVIATION 6.12 • n=4 Participants	18.7 scores on a scale STANDARD_DEVIATION 6.53 • n=21 Participants

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full analysis set included all randomized participants who received at least 1 dose of study drug. One patient in the placebo arm was excluded from all datasets due to enrollment in another clinical study. Only participants with Baseline and at least 1 post-baseline value are included. Last observation carried forward (LOCF) was used.

Outcome measures

Outcome measures
Measure	Placebo n=150 Participants Vortioxetine placebo-matching tablets, orally, once daily for up to 10 weeks.	Vortioxetine 5 mg n=142 Participants Vortioxetine 5 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.	Vortioxetine 10 mg n=147 Participants Vortioxetine 10 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.	Vortioxetine 20 mg n=149 Participants Vortioxetine 10 mg, tablets, orally, once daily for 1 week, followed by vortioxetine 20 mg, tablets, orally, once daily for 7 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily, for 2 weeks.
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score	-13.99 scores on a scale Standard Error 0.783	-14.61 scores on a scale Standard Error 0.805	-15.68 scores on a scale Standard Error 0.791	-15.82 scores on a scale Standard Error 0.786

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set, only participants with Baseline and at least 1 post-baseline value are included. LOCF 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

Outcome measures
Measure	Placebo n=150 Participants Vortioxetine placebo-matching tablets, orally, once daily for up to 10 weeks.	Vortioxetine 5 mg n=142 Participants Vortioxetine 5 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.	Vortioxetine 10 mg n=147 Participants Vortioxetine 10 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.	Vortioxetine 20 mg n=149 Participants Vortioxetine 10 mg, tablets, orally, once daily for 1 week, followed by vortioxetine 20 mg, tablets, orally, once daily for 7 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily, for 2 weeks.
Percentage of Participants With a MADRS Response at Week 8	39.3 percentage of participants	49.3 percentage of participants	54.4 percentage of participants	51.0 percentage of participants

SECONDARY outcome

Timeframe: Week 8

Population: Full analysis set, only participants with Baseline and at least 1 post-baseline value are included. LOCF 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

Outcome measures
Measure	Placebo n=150 Participants Vortioxetine placebo-matching tablets, orally, once daily for up to 10 weeks.	Vortioxetine 5 mg n=142 Participants Vortioxetine 5 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.	Vortioxetine 10 mg n=147 Participants Vortioxetine 10 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.	Vortioxetine 20 mg n=149 Participants Vortioxetine 10 mg, tablets, orally, once daily for 1 week, followed by vortioxetine 20 mg, tablets, orally, once daily for 7 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily, for 2 weeks.
Percentage of Participants in MADRS Remission at Week 8	26.7 percentage of participants	24.6 percentage of participants	29.3 percentage of participants	30.9 percentage of participants

SECONDARY outcome

Timeframe: Week 8

Population: Full analysis set, only participants with Baseline and at least 1 post-baseline value are included. LOCF was used.

The Clinical Global Impression - Global Improvement scale 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 an ANCOVA model with treatment as a fixed factor and the Baseline Clinical Global Impression-Severity of Illness (CGI-S) score as a covariate.

Outcome measures

Outcome measures
Measure	Placebo n=150 Participants Vortioxetine placebo-matching tablets, orally, once daily for up to 10 weeks.	Vortioxetine 5 mg n=142 Participants Vortioxetine 5 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.	Vortioxetine 10 mg n=148 Participants Vortioxetine 10 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.	Vortioxetine 20 mg n=150 Participants Vortioxetine 10 mg, tablets, orally, once daily for 1 week, followed by vortioxetine 20 mg, tablets, orally, once daily for 7 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily, for 2 weeks.
Mean Clinical Global Impression Scale - Improvement (CGI-I) Score at Week 8	2.54 scores on a scale Standard Error 0.087	2.37 scores on a scale Standard Error 0.089	2.27 scores on a scale Standard Error 0.088	2.36 scores on a scale Standard Error 0.087

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set, only participants with Baseline and at least 1 post-baseline value are included. LOCF was used.

The Sheehan Disability Scale assesses functional impairment in 3 domains: work/school, social life or leisure activities, and family life or home 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 an ANCOVA model with treatment as a fixed factor and the Baseline value as a covariate.

Outcome measures

Outcome measures
Measure	Placebo n=126 Participants Vortioxetine placebo-matching tablets, orally, once daily for up to 10 weeks.	Vortioxetine 5 mg n=109 Participants Vortioxetine 5 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.	Vortioxetine 10 mg n=114 Participants Vortioxetine 10 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.	Vortioxetine 20 mg n=118 Participants Vortioxetine 10 mg, tablets, orally, once daily for 1 week, followed by vortioxetine 20 mg, tablets, orally, once daily for 7 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily, for 2 weeks.
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8	-6.20 scores on a scale Standard Error 0.602	-6.38 scores on a scale Standard Error 0.647	-7.97 scores on a scale Standard Error 0.633	-7.26 scores on a scale Standard Error 0.622

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 97 other events

Deaths: 0 deaths

Vortioxetine 5 mg

Serious events: 2 serious events

Other events: 96 other events

Deaths: 0 deaths

Vortioxetine 10 mg

Serious events: 2 serious events

Other events: 93 other events

Deaths: 0 deaths

Vortioxetine 20 mg

Serious events: 3 serious events

Other events: 106 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=151 participants at risk Vortioxetine placebo-matching tablets, orally, once daily for up to 10 weeks.	Vortioxetine 5 mg n=144 participants at risk Vortioxetine 5 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.	Vortioxetine 10 mg n=148 participants at risk Vortioxetine 10 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.	Vortioxetine 20 mg n=150 participants at risk Vortioxetine 10 mg, tablets, orally, once daily for 1 week, followed by vortioxetine 20 mg, tablets, orally, once daily for 7 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily, for 2 weeks.
Infections and infestations Gastroenteritis	0.00% 0/151 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.00% 0/144 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.68% 1/148 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.00% 0/150 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.
Infections and infestations Pyelonephritis	0.00% 0/151 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.00% 0/144 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.00% 0/148 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.67% 1/150 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.
Nervous system disorders Syncope	0.00% 0/151 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.69% 1/144 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.00% 0/148 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.00% 0/150 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.
Pregnancy, puerperium and perinatal conditions Abortion missed	0.00% 0/151 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.00% 0/144 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.00% 0/148 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.67% 1/150 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.
Psychiatric disorders Suicide attempt	0.66% 1/151 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.00% 0/144 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.00% 0/148 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.67% 1/150 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.
Psychiatric disorders Depression	0.00% 0/151 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.00% 0/144 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.68% 1/148 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.00% 0/150 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.
Psychiatric disorders Suicidal ideation	0.00% 0/151 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.00% 0/144 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.00% 0/148 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.67% 1/150 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.
Renal and urinary disorders Renal colic	0.00% 0/151 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.69% 1/144 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.00% 0/148 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.	0.00% 0/150 • A treatment-emergent adverse event is defined as any AE whose onset occurs or intensity increases after the first dose of double-blind study medication through 2 weeks after the last dose of double-blind study medication. The safety analysis set included all patients who received at least 1 dose of study drug. One patient in the placebo arm was excluded due to enrollment in another clinical study. Any event spontaneously reported by the patient or observed by the investigator was recorded, irrespective of relation to study drug.

Other adverse events

Additional Information

Medical Director, Clinical Science

Takeda

Phone: 800-778-2860

Email: [email protected]

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