Trial Outcomes & Findings for Vortioxetine (Lu AA21004) 10 and 20 mg for Treatment of Major Depressive Disorder With Sexual Dysfunction (NCT NCT01364649)

Last Updated: 2014-10-09

Results Overview

The CSFQ-14 is a structured self reported questionnaire designed to measure illness- and medication-related changes in sexual functioning consisting of 14 items that measure sexual functioning as a total score (14 items) and on the subscales of pleasure (1 item), desire/frequency (2 items), desire/interest (3 items), arousal (3 items), and orgasm (3 items), rated on an 5 point scale from 1 to 5 with a total score range from 14 to 70. Higher scores reflect higher sexual functioning. A positive change from Baseline indicates that symptoms have improved. The primary analysis was based on a mixed model for repeated measurements (MMRM) analysis of covariance with treatment, center, week, treatment-by-week interaction as fixed effects, Baseline CSFQ-14 total score-by-week as covariate, and a completely unstructured covariance matrix.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

447 participants

Primary outcome timeframe

Baseline, Week 8

Results posted on

2014-10-09

Participant Flow

Participants took part in the study at 57 sites in the US and 9 sites in Canada from 16 June 12011 to 9 December 2013.

Participants with a diagnosis of major depressive disorder were enrolled equally in 1 of 2 (flexible doses of either vortioxetine (Lu AA21004) 10/20 mg once daily (QD) or escitalopram 10/20 mg QD) treatment groups.

Participant milestones

Participant milestones
Measure	Vortioxetine Vortioxetine 10 mg, tablets, orally, once daily for 1 week, then dose adjustment to a maximum 20 mg tablets, orally, once daily for up to 7 weeks. At week 8, vortioxetine placebo-matching capsules, orally, once daily for 1 week only.	Escitalopram Escitalopram 10 mg, tablets, orally, once daily for 1 week, then escitalopram dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks. At week 8, escitalopram 10 mg, capsules, capsules, orally, once daily for 1 week only
Overall Study STARTED	225	222
Overall Study COMPLETED	169	179
Overall Study NOT COMPLETED	56	43

Reasons for withdrawal

Reasons for withdrawal
Measure	Vortioxetine Vortioxetine 10 mg, tablets, orally, once daily for 1 week, then dose adjustment to a maximum 20 mg tablets, orally, once daily for up to 7 weeks. At week 8, vortioxetine placebo-matching capsules, orally, once daily for 1 week only.	Escitalopram Escitalopram 10 mg, tablets, orally, once daily for 1 week, then escitalopram dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks. At week 8, escitalopram 10 mg, capsules, capsules, orally, once daily for 1 week only
Overall Study Pretreatment Event or Adverse Event	20	14
Overall Study Lack of Efficacy	6	0
Overall Study Non-compliance with Investigational Drug	1	0
Overall Study Protocol Deviations	4	8
Overall Study Withdrawal of Consent	9	7
Overall Study Lost to Follow-up	12	13
Overall Study Other	4	1

Baseline Characteristics

Vortioxetine (Lu AA21004) 10 and 20 mg for Treatment of Major Depressive Disorder With Sexual Dysfunction

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vortioxetine n=225 Participants Vortioxetine 10 mg, tablets, orally, once daily for 1 week, then dose adjustment to a maximum 20 mg tablets, orally, once daily for up to 7 weeks. At week 8, vortioxetine placebo-matching capsules, orally, once daily for 1 week only.	Escitalopram n=222 Participants Escitalopram 10 mg, tablets, orally, once daily for 1 week, then escitalopram dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks. At week 8, escitalopram 10 mg, capsules, capsules, orally, once daily for 1 week only	Total n=447 Participants Total of all reporting groups
Age, Continuous	39.3 years STANDARD_DEVIATION 9.96 • n=99 Participants	40.2 years STANDARD_DEVIATION 10.01 • n=107 Participants	39.8 years STANDARD_DEVIATION 9.98 • n=206 Participants
Age, Customized ≤41 years	122 participants n=99 Participants	112 participants n=107 Participants	234 participants n=206 Participants
Age, Customized >41 years	103 participants n=99 Participants	110 participants n=107 Participants	213 participants n=206 Participants
Sex: Female, Male Female	128 Participants n=99 Participants	135 Participants n=107 Participants	263 Participants n=206 Participants
Sex: Female, Male Male	97 Participants n=99 Participants	87 Participants n=107 Participants	184 Participants n=206 Participants
Race/Ethnicity, Customized Hispanic or Latino	14 participants n=99 Participants	36 participants n=107 Participants	50 participants n=206 Participants
Race/Ethnicity, Customized Non-Hispanic and Non-Latino	211 participants n=99 Participants	186 participants n=107 Participants	397 participants n=206 Participants
Race/Ethnicity, Customized Caucasian (or White, including Hispanic)	178 participants n=99 Participants	181 participants n=107 Participants	359 participants n=206 Participants
Race/Ethnicity, Customized Black of African American	41 participants n=99 Participants	35 participants n=107 Participants	76 participants n=206 Participants
Race/Ethnicity, Customized Asian	4 participants n=99 Participants	3 participants n=107 Participants	7 participants n=206 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 participants n=99 Participants	3 participants n=107 Participants	4 participants n=206 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants
Region of Enrollment North America	225 participants n=99 Participants	222 participants n=107 Participants	447 participants n=206 Participants
Height	169.6 cm STANDARD_DEVIATION 9.73 • n=99 Participants	170.3 cm STANDARD_DEVIATION 8.81 • n=107 Participants	169.9 cm STANDARD_DEVIATION 9.28 • n=206 Participants
Weight	79.62 kg STANDARD_DEVIATION 16.202 • n=99 Participants	81.22 kg STANDARD_DEVIATION 16.012 • n=107 Participants	80.41 kg STANDARD_DEVIATION 16.110 • n=206 Participants
Body Mass Index (BMI)	27.54 kg/m^2 STANDARD_DEVIATION 4.352 • n=99 Participants	27.90 kg/m^2 STANDARD_DEVIATION 4.440 • n=107 Participants	27.72 kg/m^2 STANDARD_DEVIATION 4.395 • n=206 Participants
Waist Circumference	90.85 cm STANDARD_DEVIATION 13.274 • n=99 Participants	93.31 cm STANDARD_DEVIATION 13.074 • n=107 Participants	92.07 cm STANDARD_DEVIATION 13.218 • n=206 Participants
Smoking Classification Never smoked	112 participants n=99 Participants	126 participants n=107 Participants	238 participants n=206 Participants
Smoking Classification Current smoker	69 participants n=99 Participants	55 participants n=107 Participants	124 participants n=206 Participants
Smoking Classification Ex-smoker	44 participants n=99 Participants	41 participants n=107 Participants	85 participants n=206 Participants
Alcohol Consumption Never	65 participants n=99 Participants	65 participants n=107 Participants	130 participants n=206 Participants
Alcohol Consumption Once monthly or less often	86 participants n=99 Participants	82 participants n=107 Participants	168 participants n=206 Participants
Alcohol Consumption Once a week	40 participants n=99 Participants	37 participants n=107 Participants	77 participants n=206 Participants
Alcohol Consumption 2 to 6 times per week	33 participants n=99 Participants	36 participants n=107 Participants	69 participants n=206 Participants
Alcohol Consumption Daily	1 participants n=99 Participants	2 participants n=107 Participants	3 participants n=206 Participants
Changes in Sexual Functioning Questionnaire Short-Form (CSFQ-14) Total Score	36.5 scores on a scale STANDARD_DEVIATION 5.81 • n=99 Participants	36.3 scores on a scale STANDARD_DEVIATION 5.62 • n=107 Participants	36.4 scores on a scale STANDARD_DEVIATION 5.71 • n=206 Participants
Montgomery Åsberg Depression Rating Scale (MADRS) total score	7.9 scores on a scale STANDARD_DEVIATION 6.28 • n=99 Participants	8.3 scores on a scale STANDARD_DEVIATION 6.53 • n=107 Participants	8.1 scores on a scale STANDARD_DEVIATION 6.40 • n=206 Participants
Clinical Global Impression - Severity scale (CGI-S) score	2.0 scores on a scale STANDARD_DEVIATION 0.81 • n=99 Participants	2.0 scores on a scale STANDARD_DEVIATION 0.84 • n=107 Participants	2.0 scores on a scale STANDARD_DEVIATION 0.82 • n=206 Participants
Profile of Mood States (POMS) Brief Total Score	18.8 scores on a scale STANDARD_DEVIATION 19.36 • n=99 Participants	19.7 scores on a scale STANDARD_DEVIATION 19.45 • n=107 Participants	19.2 scores on a scale STANDARD_DEVIATION 19.39 • n=206 Participants

PRIMARY outcome

Timeframe: Baseline, Week 8

Population: Participants from the Full Analysis Set (FAS), defined as all participants who were randomized and received at least 1 dose of study drug, who had data available for this outcome measure.

Outcome measures

Outcome measures
Measure	Vortioxetine n=165 Participants Vortioxetine 10 mg, tablets, orally, once daily for 1 week, then dose adjustment to a maximum 20 mg tablets, orally, once daily for up to 7 weeks. At week 8, vortioxetine placebo-matching capsules, orally, once daily for 1 week only.	Escitalopram n=173 Participants Escitalopram 10 mg, tablets, orally, once daily for 1 week, then escitalopram dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks. At week 8, escitalopram 10 mg, capsules, capsules, orally, once daily for 1 week only
Change From Baseline in the Changes in Sexual Functioning Questionnaire Short-Form (CSFQ-14) Total Score at Week 8	8.8 scores on a scale Standard Error 0.64	6.6 scores on a scale Standard Error 0.64

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 4 and 6

Population: Participants from the FAS, defined as all participants who were randomized and received at least 1 dose of study drug, who had data available for this outcome measure.

Outcome measures

Outcome measures
Measure	Vortioxetine n=217 Participants Vortioxetine 10 mg, tablets, orally, once daily for 1 week, then dose adjustment to a maximum 20 mg tablets, orally, once daily for up to 7 weeks. At week 8, vortioxetine placebo-matching capsules, orally, once daily for 1 week only.	Escitalopram n=207 Participants Escitalopram 10 mg, tablets, orally, once daily for 1 week, then escitalopram dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks. At week 8, escitalopram 10 mg, capsules, capsules, orally, once daily for 1 week only
Change From Baseline in the CSFQ-14 Total Score at All Other Time Points Assessed Week 1 (n=213, 206)	2.5 scores on a scale Standard Error 0.39	2.2 scores on a scale Standard Error 0.40
Change From Baseline in the CSFQ-14 Total Score at All Other Time Points Assessed Week 2 (n=203, 200)	4.9 scores on a scale Standard Error 0.46	3.7 scores on a scale Standard Error 0.47
Change From Baseline in the CSFQ-14 Total Score at All Other Time Points Assessed Week 4 (n=187, 188)	7.0 scores on a scale Standard Error 0.55	4.8 scores on a scale Standard Error 0.55
Change From Baseline in the CSFQ-14 Total Score at All Other Time Points Assessed Week 6 (n=175, 176)	8.0 scores on a scale Standard Error 0.59	6.4 scores on a scale Standard Error 0.60

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 4, 6 and 8

Population: Participants from the FAS, defined as all participants who were randomized and received at least 1 dose of study drug, who had data available for this outcome measure. Last observation carried forward.

The CSFQ-14 is a structured self reported questionnaire designed to measure illness- and medication-related changes in sexual functioning consisting of 14 items that measure sexual functioning as a total score (14 items) and on the subscales of pleasure (1 item), desire/frequency (2 items), desire/interest (3 items), arousal (3 items), and orgasm (3 items), rated on an 5 point scale from 1 to 5 with a total score range from 14 to 70. Higher scores reflect higher sexual functioning. Normal sexual functioning is defined as a CSFQ-14 total score of \>41 for women and \>47 for men. Abnormal sexual functioning is defined as a CSFQ-14 total score of ≤41 for women and ≤47 for men. All subjects entered the study with abnormal sexual functioning. A shift to normal indicates that symptoms have improved.

Outcome measures

Outcome measures
Measure	Vortioxetine n=217 Participants Vortioxetine 10 mg, tablets, orally, once daily for 1 week, then dose adjustment to a maximum 20 mg tablets, orally, once daily for up to 7 weeks. At week 8, vortioxetine placebo-matching capsules, orally, once daily for 1 week only.	Escitalopram n=207 Participants Escitalopram 10 mg, tablets, orally, once daily for 1 week, then escitalopram dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks. At week 8, escitalopram 10 mg, capsules, capsules, orally, once daily for 1 week only
Number of Participants With Shifts in the CSFQ-14 From Abnormal to Normal at Each Week Assessed Week 4 (n=217, 206)	93 number of participants	84 number of participants
Number of Participants With Shifts in the CSFQ-14 From Abnormal to Normal at Each Week Assessed Week 1 (n=213, 205)	48 number of participants	36 number of participants
Number of Participants With Shifts in the CSFQ-14 From Abnormal to Normal at Each Week Assessed Week 2 (n=217, 206)	81 number of participants	63 number of participants
Number of Participants With Shifts in the CSFQ-14 From Abnormal to Normal at Each Week Assessed Week 6 (n=217, 206)	112 number of participants	93 number of participants
Number of Participants With Shifts in the CSFQ-14 From Abnormal to Normal at Each Week Assessed Week 8 (n=217, 206)	113 number of participants	91 number of participants

Adverse Events

Vortioxetine

Serious events: 3 serious events

Other events: 90 other events

Deaths: 0 deaths

Escitalopram

Serious events: 1 serious events

Other events: 60 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Vortioxetine n=224 participants at risk Vortioxetine 10 mg, tablets, orally, once daily for 1 week, then dose adjustment to a maximum 20 mg tablets, orally, once daily for up to 7 weeks. At week 8, vortioxetine placebo-matching capsules, orally, once daily for 1 week only.	Escitalopram n=221 participants at risk Escitalopram 10 mg, tablets, orally, once daily for 1 week, then escitalopram dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks. At week 8, escitalopram 10 mg, capsules, capsules, orally, once daily for 1 week only
Cardiac disorders Angina pectoris	0.45% 1/224 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.	0.00% 0/221 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.
Gastrointestinal disorders Mesenteric vein thrombosis	0.00% 0/224 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.	0.45% 1/221 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.
Psychiatric disorders Depression	0.89% 2/224 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.	0.00% 0/221 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.
Psychiatric disorders Anxiety	0.45% 1/224 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.	0.00% 0/221 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.
Renal and urinary disorders Nephrolithiasis	0.45% 1/224 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.	0.00% 0/221 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.

Other adverse events

Other adverse events
Measure	Vortioxetine n=224 participants at risk Vortioxetine 10 mg, tablets, orally, once daily for 1 week, then dose adjustment to a maximum 20 mg tablets, orally, once daily for up to 7 weeks. At week 8, vortioxetine placebo-matching capsules, orally, once daily for 1 week only.	Escitalopram n=221 participants at risk Escitalopram 10 mg, tablets, orally, once daily for 1 week, then escitalopram dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks. At week 8, escitalopram 10 mg, capsules, capsules, orally, once daily for 1 week only
Gastrointestinal disorders Nausea	25.0% 56/224 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.	5.4% 12/221 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.
General disorders Irritability	4.9% 11/224 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.	7.2% 16/221 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.
General disorders Fatigue	4.5% 10/224 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.	5.4% 12/221 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.
Nervous system disorders Headache	9.4% 21/224 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.	7.7% 17/221 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.
Nervous system disorders Dizziness	8.0% 18/224 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.	5.0% 11/221 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.
Psychiatric disorders Anxiety	1.8% 4/224 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.	5.4% 12/221 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.
Skin and subcutaneous tissue disorders Pruritus generalised	5.8% 13/224 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.	0.00% 0/221 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Up to 12 weeks). 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. Safety analysis set included all participants who received study drug.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

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