Trial Outcomes & Findings for Exposure, D-Cycloserine Enhancement, and Genetic Modulators in Panic Disorder (NCT NCT00790868)

Last Updated: 2018-03-07

Results Overview

The percent change in PDSS score from baseline to the relevant assessment points is the continuous primary outcome measure. The PDSS consists of seven items, each rated on a 0 to 4 scale (0 denoting none, and higher ratings reflecting greater degrees of symptom severity; for a possible range in scores from 0 to 28). In the tabular data below we present the total scores (sum of items).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

180 participants

Primary outcome timeframe

baseline, mid-TX, post-TX, follow-up visits 1-4

Results posted on

2018-03-07

Participant Flow

Participants were recruited and enrolled at Boston University (n = 68), the Institute of Living in Hartford, Connecticut (n = 59), and a combined site of Massachusetts General Hospital and Rush University Medical Center (n = 53). Results presented here are for all sites.

293 individuals completed baseline evaluations. Of these, 98 were deemed ineligible (e.g., other primary diagnosis, medication exclusion) at the initial screening visit. An additional 15 participants were not randomized due to withdrawal (n = 4), lost to follow-up (n = 10), and changes to medication (n = 1). 180 participants were randomized.

Participant milestones

Participant milestones
Measure	D-cycloserine DCS-augmented CBT D-cycloserine: 50mg	Placebo Placebo-augmented CBT Placebo: 50mg
Overall Study STARTED	88	92
Overall Study COMPLETED	82	75
Overall Study NOT COMPLETED	6	17

Reasons for withdrawal

Reasons for withdrawal
Measure	D-cycloserine DCS-augmented CBT D-cycloserine: 50mg	Placebo Placebo-augmented CBT Placebo: 50mg
Overall Study Withdrawal by Subject	4	5
Overall Study Lost to Follow-up	2	12

Baseline Characteristics

Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: baseline, mid-TX, post-TX, follow-up visits 1-4

Population: Seventeen subjects out of 92 (five during treatment and 12 during follow-up, 20% total) in the control group compared to six out of 88 (four during treatment and two during follow-up, 10% total) in the DCS group dropped out.

Outcome measures

Outcome measures
Measure	D-cycloserine n=88 Participants DCS-augmented CBT D-cycloserine: 50mg	Placebo n=92 Participants Placebo-augmented CBT Placebo: 50mg
Panic Disorder Severity Scale (PDSS) Baseline	13.30 units on a scale Standard Deviation 4.50	13.37 units on a scale Standard Deviation 3.39
Panic Disorder Severity Scale (PDSS) TX Midpoint	7.98 units on a scale Standard Deviation 3.92	8.32 units on a scale Standard Deviation 4.19
Panic Disorder Severity Scale (PDSS) TX Endpoint	5.30 units on a scale Standard Deviation 3.52	6.43 units on a scale Standard Deviation 4.63
Panic Disorder Severity Scale (PDSS) Follow-Up 1	4.76 units on a scale Standard Deviation 3.82	5.84 units on a scale Standard Deviation 4.36
Panic Disorder Severity Scale (PDSS) Follow-Up 2	4.38 units on a scale Standard Deviation 3.50	4.53 units on a scale Standard Deviation 4.03
Panic Disorder Severity Scale (PDSS) Follow-Up 3	4.46 units on a scale Standard Deviation 3.76	4.35 units on a scale Standard Deviation 4.07
Panic Disorder Severity Scale (PDSS) Follow-Up 4	3.85 units on a scale Standard Deviation 3.44	3.45 units on a scale Standard Deviation 3.78

PRIMARY outcome

Timeframe: Pre-treatment, Post-Treatment, and each follow-up sessions

Population: Full sample of 180 randomized participants

Remission status will be used as the primary categorical outcome variable. The CGI-S was used in determining whether patients met the "CGI-S of 1 or 2" component of the "remission status" criteria (i.e., zero panic attacks and CGI-S of 1 or 2 at endpoint). No values are missing because remission must be confirmed; missing status is assigned to disorder status. Hence results are for the full randomized sample.

Outcome measures

Outcome measures
Measure	D-cycloserine n=88 Participants DCS-augmented CBT D-cycloserine: 50mg	Placebo n=92 Participants Placebo-augmented CBT Placebo: 50mg
Remission Status Mid-Treatment	8 Participants	4 Participants
Remission Status Tx Endpoint	23 Participants	26 Participants
Remission Status Follow Up-1	42 Participants	34 Participants
Remission Status Follow Up-2	47 Participants	49 Participants
Remission Status Follow Up-3	48 Participants	52 Participants
Remission Status Follow Up-4	54 Participants	63 Participants

SECONDARY outcome

Timeframe: Baseline, Tx Endpoint, Each of 4 follow-up assessments

Population: Randomized participants with panic disorder

Depression severity was assessed with the MADRS, with scores ranging from 0 to 60. Higher scores indicate greater depression.

Outcome measures

Outcome measures
Measure	D-cycloserine n=88 Participants DCS-augmented CBT D-cycloserine: 50mg	Placebo n=92 Participants Placebo-augmented CBT Placebo: 50mg
Depression Severity Baseline	11.4 units on a scale Standard Deviation 8.5	11.4 units on a scale Standard Deviation 8.8
Depression Severity Treatment Endpoint	6.9 units on a scale Standard Deviation 6.8	7.8 units on a scale Standard Deviation 8.5
Depression Severity Follow Up-1	7.5 units on a scale Standard Deviation 7.5	8.1 units on a scale Standard Deviation 8.3
Depression Severity Follow Up-2	7.4 units on a scale Standard Deviation 7.4	7.1 units on a scale Standard Deviation 8.4
Depression Severity Follow Up-3	7.0 units on a scale Standard Deviation 7.6	6.1 units on a scale Standard Deviation 7.8
Depression Severity Follow Up-4	6.1 units on a scale Standard Deviation 6.5	6.7 units on a scale Standard Deviation 6.7

SECONDARY outcome

Timeframe: Baseline, Tx Endpoint, Each of 4 follow-up assessments

Population: Randomized participants

Quality of life as assessed by the Q-LES-Q. Scores range from 14-70 for total raw score, higher scores indicate higher quality of life ratings.

Outcome measures

Outcome measures
Measure	D-cycloserine n=88 Participants DCS-augmented CBT D-cycloserine: 50mg	Placebo n=92 Participants Placebo-augmented CBT Placebo: 50mg
Quality of Life Ratings Baseline	47.2 units on a scale Standard Deviation 9.3	47.1 units on a scale Standard Deviation 9.9
Quality of Life Ratings TX - Endpoint	54.4 units on a scale Standard Deviation 7.7	52.7 units on a scale Standard Deviation 9.2
Quality of Life Ratings Follow Up-1	53.9 units on a scale Standard Deviation 7.8	52.2 units on a scale Standard Deviation 9.4
Quality of Life Ratings Follow Up-2	54.3 units on a scale Standard Deviation 7.8	53.4 units on a scale Standard Deviation 9.2
Quality of Life Ratings Follow Up-3	54.6 units on a scale Standard Deviation 8.4	55.1 units on a scale Standard Deviation 8.6
Quality of Life Ratings Follow Up-4	55.6 units on a scale Standard Deviation 7.9	54.7 units on a scale Standard Deviation 8.7

SECONDARY outcome

Timeframe: Baseline, Tx Endpoint, Each of 4 follow-up assessments

Population: Randomized sample

LIFE-RIFT. For this clinician-rated measure, total scores range from 0 to 20, with higher scores indicating greater impairment

Outcome measures

Outcome measures
Measure	D-cycloserine n=88 Participants DCS-augmented CBT D-cycloserine: 50mg	Placebo n=92 Participants Placebo-augmented CBT Placebo: 50mg
Role Functioning Baseline	9.7 units on a scale Standard Deviation 3.5	9.8 units on a scale Standard Deviation 3.0
Role Functioning TX - Endpoint	7.7 units on a scale Standard Deviation 2.8	8.2 units on a scale Standard Deviation 2.8
Role Functioning Follow Up-1	7.6 units on a scale Standard Deviation 2.8	7.9 units on a scale Standard Deviation 2.7
Role Functioning Follow Up-2	7.4 units on a scale Standard Deviation 2.8	7.5 units on a scale Standard Deviation 2.6
Role Functioning Follow Up-3	7.2 units on a scale Standard Deviation 2.7	6.8 units on a scale Standard Deviation 2.4
Role Functioning Follow Up-4	7.1 units on a scale Standard Deviation 2.7	7.2 units on a scale Standard Deviation 2.6

Adverse Events

D-cycloserine

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	D-cycloserine n=88 participants at risk DCS-augmented CBT D-cycloserine: 50mg	Placebo n=92 participants at risk Placebo-augmented CBT Placebo: 50mg
Endocrine disorders Pancreatitis	1.1% 1/88 • Number of events 1 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	0.00% 0/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.
Endocrine disorders Appendicitis	0.00% 0/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	1.1% 1/92 • Number of events 1 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.
Renal and urinary disorders Kidney Infection	0.00% 0/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	0.00% 0/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.

Other adverse events

Additional Information

Michael W. Otto, Ph.D.

BostonUCRC

Phone: (617)353-9610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	D-cycloserine n=88 Participants DCS-augmented CBT D-cycloserine: 50mg	Placebo n=92 Participants Placebo-augmented CBT Placebo: 50mg	Total n=180 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=87 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.	0 Participants n=91 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.	0 Participants n=178 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.
Age, Categorical Between 18 and 65 years	85 Participants n=87 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.	90 Participants n=91 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.	175 Participants n=178 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.
Age, Categorical >=65 years	2 Participants n=87 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.	1 Participants n=91 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.	3 Participants n=178 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.
Age, Continuous	35.75 Years STANDARD_DEVIATION 11.59 • n=87 Participants • Measure Analysis Population Description: Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.	35.18 Years STANDARD_DEVIATION 12.84 • n=91 Participants • Measure Analysis Population Description: Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.	35.4 Years STANDARD_DEVIATION 12.1 • n=178 Participants • Measure Analysis Population Description: Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.
Sex: Female, Male Female	49 Participants n=88 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.	58 Participants n=92 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.	107 Participants n=180 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.
Sex: Female, Male Male	39 Participants n=88 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.	34 Participants n=92 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.	73 Participants n=180 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=88 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).	12 Participants n=92 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).	19 Participants n=180 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).
Ethnicity (NIH/OMB) Not Hispanic or Latino	81 Participants n=88 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).	79 Participants n=92 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).	160 Participants n=180 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=88 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).	1 Participants n=92 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).	1 Participants n=180 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=88 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).	0 Participants n=92 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).	0 Participants n=180 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).
Race (NIH/OMB) Asian	1 Participants n=88 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).	1 Participants n=92 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).	2 Participants n=180 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=88 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).	0 Participants n=92 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).	0 Participants n=180 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).
Race (NIH/OMB) Black or African American	4 Participants n=88 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).	5 Participants n=92 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).	9 Participants n=180 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).
Race (NIH/OMB) White	81 Participants n=88 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).	85 Participants n=92 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).	166 Participants n=180 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).
Race (NIH/OMB) More than one race	1 Participants n=88 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).	1 Participants n=92 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).	2 Participants n=180 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=88 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).	0 Participants n=92 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).	1 Participants n=180 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants (with 1 subject missing ethnicity, and 1 subject missing race due to confused reporting of these terms).
Region of Enrollment United States · Boston University	33 Participants n=88 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.	35 Participants n=92 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.	68 Participants n=180 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.
Region of Enrollment United States · Institute of Living in Hartford, Connecticut	29 Participants n=88 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.	30 Participants n=92 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.	59 Participants n=180 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.
Region of Enrollment United States · Massachusetts General Hospital/Rush	26 Participants n=88 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.	27 Participants n=92 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.	53 Participants n=180 Participants • Complete demographic information was collected for 178 participants. Some or all demographic information is missing for the remaining 2 participants.

Measure	D-cycloserine n=88 participants at risk DCS-augmented CBT D-cycloserine: 50mg	Placebo n=92 participants at risk Placebo-augmented CBT Placebo: 50mg
Gastrointestinal disorders Nausea/vomiting	6.8% 6/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	7.6% 7/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.
Gastrointestinal disorders Gastrointestinal distress	2.3% 2/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	3.3% 3/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.
General disorders Headache	4.5% 4/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	3.3% 3/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.
General disorders Fatigue	12.5% 11/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	3.3% 3/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.
General disorders Sedation	5.7% 5/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	3.3% 3/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.
General disorders Jitteriness/tremor	3.4% 3/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	1.1% 1/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.
General disorders Agitation/restlessness	2.3% 2/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	0.00% 0/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.
General disorders Dizziness/lightheadedness	5.7% 5/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	10.9% 10/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.
Psychiatric disorders Anxiety/panic	2.3% 2/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	0.00% 0/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.
Psychiatric disorders Impaired concentration	1.1% 1/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	1.1% 1/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.
General disorders Dry mouth	4.5% 4/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	1.1% 1/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.
Eye disorders Blurred vision	1.1% 1/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	1.1% 1/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.
Cardiac disorders Tachycardia	2.3% 2/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	0.00% 0/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.
General disorders Paresthesias	1.1% 1/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	4.3% 4/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.
Respiratory, thoracic and mediastinal disorders Shortness of breath	4.5% 4/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	2.2% 2/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.
Skin and subcutaneous tissue disorders Itching	2.3% 2/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	0.00% 0/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.
General disorders Chills	1.1% 1/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	0.00% 0/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.
Psychiatric disorders Derealization	1.1% 1/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	1.1% 1/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.
Reproductive system and breast disorders Menstrual irregularity	1.1% 1/88 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.	1.1% 1/92 • Adverse events were monitored and elicited by open questioning of the study clinician, assessing adverse events occurring over the last hour as well as during the week following the last dose of DCS. AEs and SAEs were informally assessed up to the 6-month follow-up.