Trial Outcomes & Findings for Nepicastat for Posttraumatic Stress Disorder (PTSD) in OIF/OEF Veterans (NCT NCT00659230)

NCT ID: NCT00659230

Last Updated: 2017-10-13

Results Overview

The Clinician Administered PTSD Scale subscore D (CAPS-D) measures the hyperarousal cluster for PTSD symptoms (5 items). Higher scores indicate greater severity. Range for CAPS-D is zero to 40. The CAPS has acceptable test-retest reliability (0.98), sensitivity (0.84), specificity (0.95), internal consistency (0.76-0.88) and validity (κ=0.78).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 100 participants
• Primary outcome timeframe: Baseline, week 2, 4 and 6
• Results posted on: 2017-10-13

Participant Flow

Participant milestones

Measure	Placebo Arm 1 Placebo: 100-800mg placebo	Nepicastat Arm 2 Nepicastat: 100-800mg
Overall Study STARTED	51	49
Overall Study COMPLETED	42	37
Overall Study NOT COMPLETED	9	12

Reasons for withdrawal

Measure	Placebo Arm 1 Placebo: 100-800mg placebo	Nepicastat Arm 2 Nepicastat: 100-800mg
Overall Study Lost to Follow-up	2	5
Overall Study Lost source documentation	5	4
Overall Study Did not return post-randomization	2	3

Baseline Characteristics

Nepicastat for Posttraumatic Stress Disorder (PTSD) in OIF/OEF Veterans

Baseline characteristics by cohort

Measure	Placebo n=46 Participants Arm 1 Placebo: 100-800mg placebo	Nepicastat n=45 Participants Arm 2 Nepicastat: 100-800mg	Total n=91 Participants Total of all reporting groups
Age, Continuous	36.61 years STANDARD_DEVIATION 10.49 • n=5 Participants	39.33 years STANDARD_DEVIATION 11.01 • n=7 Participants	37.96 years STANDARD_DEVIATION 10.88 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants	44 Participants n=7 Participants	86 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	44 Participants n=5 Participants	40 Participants n=7 Participants	84 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	22 Participants n=5 Participants	22 Participants n=7 Participants	44 Participants n=5 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants	16 Participants n=7 Participants	37 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	7 Participants n=7 Participants	10 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
Region of Enrollment United States	46 participants n=5 Participants	45 participants n=7 Participants	91 participants n=5 Participants
CAPS-D Score (primary outcome)	25.59 units on a scale STANDARD_DEVIATION 6.17 • n=5 Participants	26.07 units on a scale STANDARD_DEVIATION 6.01 • n=7 Participants	25.82 units on a scale STANDARD_DEVIATION 6.06 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, week 2, 4 and 6

Population: Participants who returned for at least one post-randomization visit and had source documentation (in placebo group 2 did not return and the source documentation for 5 participants was lost; for nepicastat group 3 did not return and the source documentation for 4 participants was lost).

The Clinician Administered PTSD Scale subscore D (CAPS-D) measures the hyperarousal cluster for PTSD symptoms (5 items). Higher scores indicate greater severity. Range for CAPS-D is zero to 40. The CAPS has acceptable test-retest reliability (0.98), sensitivity (0.84), specificity (0.95), internal consistency (0.76-0.88) and validity (κ=0.78).

Outcome measures

Measure	Placebo n=44 Participants Arm 1 Placebo: 100-800mg placebo	Nepicastat n=42 Participants Arm 2 Nepicastat: 100-800mg
Clinician Administered PTSD Scale Subscore D (Hyperarousal) Baseline	25.59 units on a scale Standard Deviation 6.17	26.07 units on a scale Standard Deviation 6.01
Clinician Administered PTSD Scale Subscore D (Hyperarousal) Week 2	21.20 units on a scale Standard Deviation 7.59	22.07 units on a scale Standard Deviation 7.95
Clinician Administered PTSD Scale Subscore D (Hyperarousal) Week 4	19.78 units on a scale Standard Deviation 8.27	21.15 units on a scale Standard Deviation 8.13
Clinician Administered PTSD Scale Subscore D (Hyperarousal) Week 6	19.57 units on a scale Standard Deviation 8.55	21.62 units on a scale Standard Deviation 9.17

SECONDARY outcome

Timeframe: Baseline, week 2,4, and 6

Population: Participants who returned for at least one post-randomization visit and had source documentation (in placebo group 2 did not return and the source documentation for 5 participants was lost; for nepicastat group 3 did not return and the source documentation for 4 participants was lost).

The Clinician Administered PTSD Scale (CAPS) measures the full spectrum of PTSD symptoms. Higher scores indicate greater severity. Range for CAPS is zero to 136. The CAPS has acceptable test-retest reliability (0.98), sensitivity (0.84), specificity (0.95), internal consistency (0.76-0.88) and validity (κ=0.78).

Outcome measures

Measure	Placebo n=44 Participants Arm 1 Placebo: 100-800mg placebo	Nepicastat n=42 Participants Arm 2 Nepicastat: 100-800mg
Clinician Administered PTSD Scale Total Score Baseline	74.52 units on a scale Standard Deviation 16.73	77.18 units on a scale Standard Deviation 16.55
Clinician Administered PTSD Scale Total Score Week 2	61.82 units on a scale Standard Deviation 25.02	60.17 units on a scale Standard Deviation 24.72
Clinician Administered PTSD Scale Total Score Week 4	52.61 units on a scale Standard Deviation 27.17	60.26 units on a scale Standard Deviation 27.59
Clinician Administered PTSD Scale Total Score Week 6	58.22 units on a scale Standard Deviation 28.37	52.95 units on a scale Standard Deviation 25.81

SECONDARY outcome

Timeframe: 6 weeks

Population: Participants who returned for at least one post-randomization visit and had source documentation (in placebo group 2 did not return and the source documentation for 5 participants was lost; for nepicastat group 3 did not return and the source documentation for 4 participants was lost).

The Clinician Administered PTSD Subscale B (CAPS-B) measures the re-experiencing cluster of PTSD symptoms. Higher scores indicate greater severity. Range for CAPS-B is zero to 40. The CAPS has acceptable test-retest reliability (0.98), sensitivity (0.84), specificity (0.95), internal consistency (0.76-0.88) and validity (κ=0.78). Blake, D.D., Weathers, F.W., Nagy, L.M., Kaloupek, D.G., Gusman, F.D., Charney, D.S., Kean, T.M., 1995, The development of a clinician-administered PTSD scale. Journal of Traumatic Stress, 8:75-90.

Outcome measures

Measure	Placebo n=44 Participants Arm 1 Placebo: 100-800mg placebo	Nepicastat n=42 Participants Arm 2 Nepicastat: 100-800mg
Clinician Administered PTSD Scale Subscale B Score Baseline	20.37 units on a scale Standard Deviation 7.26	20.41 units on a scale Standard Deviation 8.46
Clinician Administered PTSD Scale Subscale B Score Week 2	16.95 units on a scale Standard Deviation 9.77	14.14 units on a scale Standard Deviation 8.97
Clinician Administered PTSD Scale Subscale B Score Week 4	11.51 units on a scale Standard Deviation 10.02	14.59 units on a scale Standard Deviation 9.75
Clinician Administered PTSD Scale Subscale B Score Week 6	12.64 units on a scale Standard Deviation 10.04	15.27 units on a scale Standard Deviation 10.27

SECONDARY outcome

Timeframe: Baseline, week 2, 4, and 6

Population: Participants who returned for at least one post-randomization visit and had source documentation (in placebo group 2 did not return and the source documentation for 5 participants was lost; for nepicastat group 3 did not return and the source documentation for 4 participants was lost).

The Clinician Administered PTSD Subscale C (CAPS-C) measures the Avoidance and emotional numbing cluster of PTSD symptoms. Higher scores indicate greater severity. Range for CAPS-C is zero to 56. The CAPS has acceptable test-retest reliability (0.98), sensitivity (0.84), specificity (0.95), internal consistency (0.76-0.88) and validity (κ=0.78).

Outcome measures

Measure	Placebo n=44 Participants Arm 1 Placebo: 100-800mg placebo	Nepicastat n=42 Participants Arm 2 Nepicastat: 100-800mg
Clinician Administered PTSD Scale Subscale C Score Week 4	21.32 units on a scale Standard Deviation 12.82	24.51 units on a scale Standard Deviation 13.06
Clinician Administered PTSD Scale Subscale C Score Baseline	29.02 units on a scale Standard Deviation 8.03	30.70 units on a scale Standard Deviation 7.37
Clinician Administered PTSD Scale Subscale C Score Week 2	23.66 units on a scale Standard Deviation 12.18	24.39 units on a scale Standard Deviation 11.41
Clinician Administered PTSD Scale Subscale C Score Week 6	20.74 units on a scale Standard Deviation 12.21	21.32 units on a scale Standard Deviation 12.11

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 25 other events

Deaths: 0 deaths

Nepicastat

Serious events: 2 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=46 participants at risk Arm 1 Placebo: 100-800mg placebo	Nepicastat n=45 participants at risk Arm 2 Nepicastat: 100-800mg
Cardiac disorders Chest Pain	2.2% 1/46 • Number of events 2 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	2.2% 1/45 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Psychiatric disorders Psychiatric Inpatient	4.3% 2/46 • Number of events 2 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	2.2% 1/45 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.

Other adverse events

Measure	Placebo n=46 participants at risk Arm 1 Placebo: 100-800mg placebo	Nepicastat n=45 participants at risk Arm 2 Nepicastat: 100-800mg
Ear and labyrinth disorders Ear Pain	0.00% 0/46 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	2.2% 1/45 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Eye disorders Eye Pain	2.2% 1/46 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	2.2% 1/45 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Gastrointestinal disorders Diarrhea	6.5% 3/46 • Number of events 3 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	15.6% 7/45 • Number of events 7 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Eye disorders Dry Eye	0.00% 0/46 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	2.2% 1/45 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Gastrointestinal disorders Gastroesophageal Reflux	4.3% 2/46 • Number of events 2 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	0.00% 0/45 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Gastrointestinal disorders Nausea	6.5% 3/46 • Number of events 3 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	2.2% 1/45 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Gastrointestinal disorders Vomitting	2.2% 1/46 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	0.00% 0/45 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Gastrointestinal disorders Stomach Pain	4.3% 2/46 • Number of events 2 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	2.2% 1/45 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Gastrointestinal disorders Dental Caries	2.2% 1/46 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	4.4% 2/45 • Number of events 2 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Gastrointestinal disorders Dry Mouth	6.5% 3/46 • Number of events 3 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	0.00% 0/45 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
General disorders Edema Face	0.00% 0/46 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	2.2% 1/45 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
General disorders Fatigue	6.5% 3/46 • Number of events 3 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	2.2% 1/45 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Infections and infestations Gastroenteritis	4.3% 2/46 • Number of events 2 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	0.00% 0/45 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Infections and infestations Flu-like	10.9% 5/46 • Number of events 5 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	8.9% 4/45 • Number of events 5 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Infections and infestations sinusitis	2.2% 1/46 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	4.4% 2/45 • Number of events 2 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Infections and infestations MRSA staphylococcal infection	0.00% 0/46 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	2.2% 1/45 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Injury, poisoning and procedural complications injury to extremity	2.2% 1/46 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	2.2% 1/45 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Musculoskeletal and connective tissue disorders muscle twitch	2.2% 1/46 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	0.00% 0/45 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Musculoskeletal and connective tissue disorders muscle spasm	2.2% 1/46 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	0.00% 0/45 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Musculoskeletal and connective tissue disorders arthralgia	4.3% 2/46 • Number of events 2 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	8.9% 4/45 • Number of events 4 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Nervous system disorders headache	15.2% 7/46 • Number of events 7 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	20.0% 9/45 • Number of events 9 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Nervous system disorders dysgeusia (taste changes)	2.2% 1/46 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	0.00% 0/45 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Nervous system disorders paraesthesia	0.00% 0/46 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	2.2% 1/45 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Nervous system disorders memory problems	0.00% 0/46 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	2.2% 1/45 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Psychiatric disorders insomnia	2.2% 1/46 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	0.00% 0/45 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Respiratory, thoracic and mediastinal disorders shortness of breath	2.2% 1/46 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	0.00% 0/45 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Respiratory, thoracic and mediastinal disorders epistaxis	0.00% 0/46 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	2.2% 1/45 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Skin and subcutaneous tissue disorders rash acneiform	2.2% 1/46 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	4.4% 2/45 • Number of events 2 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Skin and subcutaneous tissue disorders rash	2.2% 1/46 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	2.2% 1/45 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Skin and subcutaneous tissue disorders pruritus	0.00% 0/46 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	2.2% 1/45 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Surgical and medical procedures tongue lesion removed	2.2% 1/46 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	0.00% 0/45 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Vascular disorders superficial thrombophlebitis	2.2% 1/46 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	0.00% 0/45 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Vascular disorders hypertension	0.00% 0/46 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	2.2% 1/45 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.
Vascular disorders hot flash	0.00% 0/46 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.	2.2% 1/45 • Number of events 1 • During six-week placebo-controlled phase. Adverse events were defined the same as clinicaltrials.gov. Adverse events were systematically assessed at each research visit for type of adverse event, length of time, severity, action taken, and relatedness to study medication. The source documentation was lost for 9 participants at one site (5 placebo and 4 nepicastat) and were not included in safety analysis.

Additional Information

Lori L. Davis, MD

Tuscaloosa VA Medical Center

Phone: 205-554-2000

Email: lori.davis@va.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place