Trial Outcomes & Findings for Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism (NCT NCT01337700)

Last Updated: 2020-02-27

Results Overview

Change will be measured in each subject's score on the Conners Adults Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale from baseline through study end (week 12).Higher values represent a worse outcome. The raw scores are converted to T-scores for each scale and sub-scale which are then compared against the mean. Higher values represent a worse outcome. A T-score of 50 is the mean of a relevant reference population. A T-score above 65 indicates a moderate to severe problem. For example, Row 1 is the mean of baseline T-scores for the Inattention/ Memory subscale and Row 2 is the mean of week 12 T-scores for the Inattention/ Memory subscale. The difference between these two means is used to measure the change from baseline through week 12 for both the groups.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

10 participants

Primary outcome timeframe

Baseline and Week 12 scores

Results posted on

2020-02-27

Participant Flow

Participant milestones

Participant milestones
Measure	Milnacipran Milnacipran: Patients will receive a titrated dose of milnacipran increasing to a maximum of 100mg a day over the 12 week study period. Dosing will be based on a fixed schedule that will be monitored using a side effect profile.	Placebo Placebo: Subjects will be given placebo tablets at dosing corresponding to the fixed schedule between 12.5mg and 100mg.
Overall Study STARTED	5	5
Overall Study COMPLETED	5	5
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Milnacipran n=5 Participants Milnacipran: Patients will receive a titrated dose of milnacipran increasing to a maximum of 100mg a day over the 12 week study period. Dosing will be based on a fixed schedule that will be monitored using a side effect profile.	Placebo n=5 Participants Placebo: Subjects will be given placebo tablets at dosing corresponding to the fixed schedule between 12.5mg and 100mg.	Total n=10 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	25 years STANDARD_DEVIATION 3.391 • n=5 Participants	25.2 years STANDARD_DEVIATION 9.149 • n=7 Participants	25.10 years STANDARD_DEVIATION 6.506 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Severity of Illness	4 units on a scale n=5 Participants	5 units on a scale n=7 Participants	4.5 units on a scale n=5 Participants
Aberrant Behavior Checklist - Hyperactivity Scale (ABC-H)	19 units on a scale n=5 Participants	9.8 units on a scale n=7 Participants	14.4 units on a scale n=5 Participants
CAARS Inattention/Memory T Score	68.6 T score n=5 Participants	71.8 T score n=7 Participants	70.2 T score n=5 Participants
CAARS Hyperactivity/Restlessness T Score	55 T score n=5 Participants	50.8 T score n=7 Participants	52.9 T score n=5 Participants
CAARS Impulsivity/Emotional Labiality T Score	55.2 T score n=5 Participants	49.2 T score n=7 Participants	52.2 T score n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12 scores

Outcome measures

Outcome measures
Measure	Milnacipran n=5 Participants Milnacipran: Patients will receive a titrated dose of milnacipran increasing to a maximum of 200mg a day over the 12 week study period. Dosing will be based on a fixed schedule that will be monitored using a side effect profile.	Placebo n=5 Participants Placebo: Subjects will be given placebo tablets at dosing corresponding to the fixed schedule between 12.5mg and 100mg.
Change in Score on Conners Adults Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale Baseline: T-SCORES- Inattention/Memory	68.6 T-score Standard Deviation 14.83	71.8 T-score Standard Deviation 5.81
Change in Score on Conners Adults Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale Week 12: T-SCORES- Inattention/Memory	53.4 T-score Standard Deviation 13.05	57 T-score Standard Deviation 20.22
Change in Score on Conners Adults Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale Baseline: T-SCORES- Hyperactivity/Restlessness	55 T-score Standard Deviation 12.63	50.8 T-score Standard Deviation 8.76
Change in Score on Conners Adults Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale Week 12:T-SCORES -Hyperactivity/Restlessness	44.8 T-score Standard Deviation 8.76	39.8 T-score Standard Deviation 7.56
Change in Score on Conners Adults Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale Baseline: T-SCORES- Impulsivity/Emotional Lability	55.2 T-score Standard Deviation 7.66	49.2 T-score Standard Deviation 5.89
Change in Score on Conners Adults Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale Week 12: T-SCORES- Impulsivity/Emotional Lability	47.8 T-score Standard Deviation 6.22	43.6 T-score Standard Deviation 13.90

PRIMARY outcome

Timeframe: Baseline to Endpoint - 12 weeks

The Aberrant Behavior Checklist is an informant-based questionnaire consisting of 58 items subdivided amongst 5 scales: irritability, lethargy and social withdrawal, stereotypic behavior, hyperactivity/non-compliance, and inappropriate speech \[34\]. A score for each item ranges from 0 indicating "no problem" to 3 indicating "severe problem". Scale scores are calculated by summing the items within that scale. Higher scores indicate greater impairment.Reported Data is for change in ABC-H from baseline to endpoint (week 0 to week 12).This data is specifically looking at the hyperactivity scale which is 16 items with each item ranging from 0-3 making total scores 0-48.

Outcome measures

Outcome measures
Measure	Milnacipran n=5 Participants Milnacipran: Patients will receive a titrated dose of milnacipran increasing to a maximum of 200mg a day over the 12 week study period. Dosing will be based on a fixed schedule that will be monitored using a side effect profile.	Placebo n=5 Participants Placebo: Subjects will be given placebo tablets at dosing corresponding to the fixed schedule between 12.5mg and 100mg.
Change in Hyperactivity as Measured by Aberrant Behavior Checklist - Hyperactivity Scale	-10.4 units on a scale Standard Deviation 12.46	-4.2 units on a scale Standard Deviation 7.26

SECONDARY outcome

Timeframe: screening, baseline, weeks 2,4,6,8,10,12

The CGI-I reflects the rater's impression of the subject's current autism severity on a 7-point scale ranging from Much Improved (1) to Much worse (5).

Outcome measures

Outcome measures
Measure	Milnacipran n=5 Participants Milnacipran: Patients will receive a titrated dose of milnacipran increasing to a maximum of 200mg a day over the 12 week study period. Dosing will be based on a fixed schedule that will be monitored using a side effect profile.	Placebo n=5 Participants Placebo: Subjects will be given placebo tablets at dosing corresponding to the fixed schedule between 12.5mg and 100mg.
Change in Autism Severity Levels Based on the Clinical Global Impressions Scale Much Improved	1 Participants	1 Participants
Change in Autism Severity Levels Based on the Clinical Global Impressions Scale Minimally Improved	1 Participants	1 Participants
Change in Autism Severity Levels Based on the Clinical Global Impressions Scale No Change	3 Participants	2 Participants
Change in Autism Severity Levels Based on the Clinical Global Impressions Scale Minimally Worse	0 Participants	1 Participants
Change in Autism Severity Levels Based on the Clinical Global Impressions Scale Much Worse	0 Participants	0 Participants

SECONDARY outcome

Timeframe: baseline, weeks 2,4,6,8,10,12

This scale has been shown to be a sensitive outcome measure in autism trials of repetitive behaviors. Data for secondary outcome not analyzed due to lack of significance in primary outcomes measured. * scale range: 0 - 40 total, 0 - 7 subclinical, 8-15 mild, 16 - 23 moderate, 24 - 31 severe, 32 - 40 extreme * score interpretation: Higher overall scores reflect increasing symptom severity.

Outcome measures

Outcome measures
Measure	Milnacipran n=5 Participants Milnacipran: Patients will receive a titrated dose of milnacipran increasing to a maximum of 200mg a day over the 12 week study period. Dosing will be based on a fixed schedule that will be monitored using a side effect profile.	Placebo n=5 Participants Placebo: Subjects will be given placebo tablets at dosing corresponding to the fixed schedule between 12.5mg and 100mg.
Change in Repetitive Behaviors Using YBOCS-Compulsion and Rigidity Subscale Week 12	12.4 score on a scale Standard Deviation 4.41	12 score on a scale Standard Deviation 3.03
Change in Repetitive Behaviors Using YBOCS-Compulsion and Rigidity Subscale Week 4	11.6 score on a scale Standard Deviation 5.08	13.2 score on a scale Standard Deviation 3.12
Change in Repetitive Behaviors Using YBOCS-Compulsion and Rigidity Subscale Week 6	11.8 score on a scale Standard Deviation 4.12	12 score on a scale Standard Deviation 1.79
Change in Repetitive Behaviors Using YBOCS-Compulsion and Rigidity Subscale Baseline	12.2 score on a scale Standard Deviation 5.45	12 score on a scale Standard Deviation 2.75
Change in Repetitive Behaviors Using YBOCS-Compulsion and Rigidity Subscale Week 2	10 score on a scale Standard Deviation 6.16	12.2 score on a scale Standard Deviation 1.32
Change in Repetitive Behaviors Using YBOCS-Compulsion and Rigidity Subscale Week 8	10.4 score on a scale Standard Deviation 3.93	9.8 score on a scale Standard Deviation 4.99
Change in Repetitive Behaviors Using YBOCS-Compulsion and Rigidity Subscale Week 10	11.6 score on a scale Standard Deviation 4.03	12.8 score on a scale Standard Deviation 1.17

SECONDARY outcome

Timeframe: baseline, weeks 2,4,6,8,10,12

This scale is shown to be sensitive to change in adults with autism, and related to amygdala function. Higher scores mean a better outcome.A clinical tool measuring emotion recognition through facial expression, voice and posture. 1. Child faces 2 (range 0 - 100, higher values reflecting higher % of errors) 2. Adult faces 2 (range 0 - 100, higher values reflecting higher % of errors) 3. Child paralanguage 2 (range 0 - 100, higher values reflecting higher % of errors) 4. Adult paralanguage 2 (range 0 - 100, higher values reflecting higher % of errors) Errors are counted and organized by pre-determined affect and intensity. Subtests considered separately.

Outcome measures

Outcome measures
Measure	Milnacipran n=5 Participants Milnacipran: Patients will receive a titrated dose of milnacipran increasing to a maximum of 200mg a day over the 12 week study period. Dosing will be based on a fixed schedule that will be monitored using a side effect profile.	Placebo n=5 Participants Placebo: Subjects will be given placebo tablets at dosing corresponding to the fixed schedule between 12.5mg and 100mg.
Change in Diagnostic Analysis of Nonverbal Activity-2 ADULT FACIAL EXPRESSIONS: (DANVA2-AF) Baseline	16.5 score on a scale Standard Deviation 2.18	18.5 score on a scale Standard Deviation 3.5
Change in Diagnostic Analysis of Nonverbal Activity-2 ADULT FACIAL EXPRESSIONS: (DANVA2-AF) Week 2	19.25 score on a scale Standard Deviation 1.48	19 score on a scale Standard Deviation 2.2
Change in Diagnostic Analysis of Nonverbal Activity-2 ADULT FACIAL EXPRESSIONS: (DANVA2-AF) Week 4	19.6 score on a scale Standard Deviation 3.5	19.6 score on a scale Standard Deviation 2.06
Change in Diagnostic Analysis of Nonverbal Activity-2 ADULT FACIAL EXPRESSIONS: (DANVA2-AF) Week 6	19.4 score on a scale Standard Deviation 4.08	20 score on a scale Standard Deviation 1.41
Change in Diagnostic Analysis of Nonverbal Activity-2 ADULT FACIAL EXPRESSIONS: (DANVA2-AF) Week 8	17 score on a scale Standard Deviation 3.74	19.2 score on a scale Standard Deviation 1.94
Change in Diagnostic Analysis of Nonverbal Activity-2 ADULT FACIAL EXPRESSIONS: (DANVA2-AF) Week 10	17.25 score on a scale Standard Deviation 3.77	20 score on a scale Standard Deviation 0.81
Change in Diagnostic Analysis of Nonverbal Activity-2 ADULT FACIAL EXPRESSIONS: (DANVA2-AF) Week 12	18 score on a scale Standard Deviation 2.83	18.8 score on a scale Standard Deviation 2.78

Adverse Events

Milnacipran

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Eric Hollander, MD

Montefiore Medical Center, Albert Eins

Phone: 7189204287

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Milnacipran n=5 participants at risk Milnacipran: Patients will receive a titrated dose of milnacipran increasing to a maximum of 100mg a day over the 12 week study period. Dosing will be based on a fixed schedule that will be monitored using a side effect profile.	Placebo n=5 participants at risk Placebo: Subjects will be given placebo tablets at dosing corresponding to the fixed schedule between 12.5mg and 100mg.
General disorders Fatigue	40.0% 2/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.	0.00% 0/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
General disorders Headache	40.0% 2/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.	40.0% 2/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
General disorders Nightmares	0.00% 0/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.	40.0% 2/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
General disorders Weight loss	20.0% 1/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.	0.00% 0/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
General disorders Abdominal Cramping	20.0% 1/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.	0.00% 0/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
Gastrointestinal disorders Anal Fissure	20.0% 1/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.	0.00% 0/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
General disorders Dizziness	20.0% 1/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.	0.00% 0/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
Gastrointestinal disorders Gastroenteritis	20.0% 1/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.	0.00% 0/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
General disorders Gum Pain	20.0% 1/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.	0.00% 0/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
General disorders Hemorrhoids	20.0% 1/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.	0.00% 0/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
General disorders Insomnia	20.0% 1/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.	0.00% 0/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
General disorders Lethargy	0.00% 0/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.	20.0% 1/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
General disorders Lightheadedness	0.00% 0/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.	20.0% 1/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
General disorders Menstrual Cramps	0.00% 0/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.	20.0% 1/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
General disorders Nausea	20.0% 1/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.	0.00% 0/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
General disorders Sleep Disruption	20.0% 1/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.	0.00% 0/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
General disorders Stomachache	0.00% 0/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.	20.0% 1/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
General disorders Somnolence	20.0% 1/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.	0.00% 0/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
Infections and infestations Upper Respiratory Infection	60.0% 3/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.	20.0% 1/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
General disorders Vomiting	0.00% 0/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.	20.0% 1/5 • Adverse event data was collected from baseline to endpoint, for 12 weeks total. By definition, serious Adverse Events includes adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.