Trial Outcomes & Findings for Neurophysiological and Acute Pharmacological Studies in FXS Patients (NCT NCT02998151)

NCT ID: NCT02998151

Last Updated: 2021-11-26

Results Overview

EEG relative gamma power at rest was calculated as the percent of power in the gamma frequencies relative to the sum of power in all frequency bands, averaged across electrodes, and calculated separately at pre-dose and post-dose timepoints. To assess the impact of drug, the pre-dose relative gamma power was subtracted from post-dose relative gamma power. Higher numbers indicate more relative gamma power post-dose; lower numbers indicate more relative gamma power pre-dose.

• Recruitment status: COMPLETED
• Study phase: EARLY_PHASE1
• Target enrollment: 29 participants
• Primary outcome timeframe: Pre-dose, 4-hour post-dose
• Results posted on: 2021-11-26

Participant Flow

Participants engaged in a baseline visit to gather preliminary data and ensure study compliance. Participants were then randomly assigned to different sequences for receiving acamprosate, lovastatin, minocycline, baclofen, and placebo. There was a 2-week washout period between visits.

Participant milestones

Measure	All Study Participants This study was designed as a 4-intervention crossover, with all study participants receiving all possible interventions. These were originally placebo, acamprosate, minocycline, and lovastatin. Midway through the study (n=16) it was determined that acamprosate was undetectable in serum and this arm was replaced by baclofen. Remaining participants (n=13) received baclofen and 5 participants were re-enrolled to receive baclofen.
Overall Study STARTED	29
Overall Study Placebo	27
Overall Study Acamprosate	16
Overall Study Lovastatin	29
Overall Study Minocycline	27
Overall Study Baclofen	18
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	24

Reasons for withdrawal

Measure	All Study Participants This study was designed as a 4-intervention crossover, with all study participants receiving all possible interventions. These were originally placebo, acamprosate, minocycline, and lovastatin. Midway through the study (n=16) it was determined that acamprosate was undetectable in serum and this arm was replaced by baclofen. Remaining participants (n=13) received baclofen and 5 participants were re-enrolled to receive baclofen.
Overall Study Withdrawal by Subject	3
Overall Study Participant declined to re-enroll for baclofen	8
Overall Study Participant was not offered acamprosate; acamprosate was discontinued and replaced with baclofen	13

Baseline Characteristics

One participant did not complete the Woodcock Johnson.

Baseline characteristics by cohort

Measure	All Study Participants n=29 Participants Participants received, in random order, a single dose of placebo, acamprosate, lovastatin, minocycline, or baclofen, with a two-week washout period between doses. Midway through the study (n=16) it was determined that acamprosate was undetectable in serum and this intervention was replaced by baclofen. Remaining participants (n=13) received baclofen and 5 participants were re-enrolled to receive baclofen or a second round of placebo, so investigators and participants would remain blinded to drug status during the baclofen visit. The second round of placebo was not analyzed.
Age, Categorical <=18 years	0 Participants n=29 Participants
Age, Categorical Between 18 and 65 years	29 Participants n=29 Participants
Age, Categorical >=65 years	0 Participants n=29 Participants
Age, Continuous	24.71 years STANDARD_DEVIATION 8.56 • n=29 Participants
Sex: Female, Male Female	9 Participants n=29 Participants
Sex: Female, Male Male	20 Participants n=29 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=29 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=29 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=29 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=29 Participants
Race (NIH/OMB) Asian	0 Participants n=29 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=29 Participants
Race (NIH/OMB) Black or African American	2 Participants n=29 Participants
Race (NIH/OMB) White	25 Participants n=29 Participants
Race (NIH/OMB) More than one race	1 Participants n=29 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=29 Participants
Region of Enrollment United States	29 participants n=29 Participants
Woodcock Johnson Test of Cognitive Abilities - Auditory Attention Task	30.89 scores on a scale STANDARD_DEVIATION 4.92 • n=28 Participants • One participant did not complete the Woodcock Johnson.

PRIMARY outcome

Timeframe: Pre-dose, 4-hour post-dose

Population: Missing 1 placebo, 1 lovastatin who contributed data with excessive movement or other artifact, or were unable to complete the task.

EEG relative gamma power at rest was calculated as the percent of power in the gamma frequencies relative to the sum of power in all frequency bands, averaged across electrodes, and calculated separately at pre-dose and post-dose timepoints. To assess the impact of drug, the pre-dose relative gamma power was subtracted from post-dose relative gamma power. Higher numbers indicate more relative gamma power post-dose; lower numbers indicate more relative gamma power pre-dose.

Outcome measures

Measure	Placebo n=26 Participants Placebo: placebo pill	Acamprosate n=16 Participants Acamprosate: two 666mg pills	Lovastatin n=28 Participants Lovastatin: two 20mg pills	Minocycline n=27 Participants Minocycline: two 135mg pills	Baclofen n=18 Participants Baclofen: one 30mg pill
Change in EEG Relative Gamma Power	0.0024 percent of power in gamma frequencies Standard Deviation .0265	-0.0077 percent of power in gamma frequencies Standard Deviation 0.0252	-0.0039 percent of power in gamma frequencies Standard Deviation 0.0225	0.0019 percent of power in gamma frequencies Standard Deviation 0.0235	-0.0160 percent of power in gamma frequencies Standard Deviation 0.0346

PRIMARY outcome

Timeframe: 4-hour post-dose

Population: CGI-I was not collected for one participant on their minocycline day and another participant on their baclofen day.

The Clinical Global Impressions - Improvement (CGI-I) requires the clinician to assess how much the patient's illness has changed relative to pre-dose, from 1 (very much improved) to 7 (very much worse).

Outcome measures

Measure	Placebo n=27 Participants Placebo: placebo pill	Acamprosate n=16 Participants Acamprosate: two 666mg pills	Lovastatin n=29 Participants Lovastatin: two 20mg pills	Minocycline n=26 Participants Minocycline: two 135mg pills	Baclofen n=17 Participants Baclofen: one 30mg pill
Clinical Global Impressions-Improvement	3.70 score on a scale Standard Deviation .61	3.88 score on a scale Standard Deviation .62	3.97 score on a scale Standard Deviation .50	3.81 score on a scale Standard Deviation .49	3.94 score on a scale Standard Deviation .43

SECONDARY outcome

Timeframe: 4-hour post-dose

Population: Data is missing from 2 placebo, 1 acamprosate, 1 lovastatin, 2 minocycline, and 1 baclofen.

Woodcock Johnson Test of Cognitive Abilities III Auditory Attention subscale. Participants must identify orally presented words amid increasingly intense background noise. The scores for this subtask range from 0-50, with higher scores indicating a better outcome. Raw scores for this subscale are reported (rather than standard scores, or age- or grade-equivalents).

Outcome measures

Measure	Placebo n=25 Participants Placebo: placebo pill	Acamprosate n=15 Participants Acamprosate: two 666mg pills	Lovastatin n=28 Participants Lovastatin: two 20mg pills	Minocycline n=25 Participants Minocycline: two 135mg pills	Baclofen n=17 Participants Baclofen: one 30mg pill
Woodcock Johnson Test of Cognitive Abilities - Auditory Attention Task	32.84 score on a scale Standard Deviation 5.77	33.07 score on a scale Standard Deviation 5.48	32.93 score on a scale Standard Deviation 5.31	33.24 score on a scale Standard Deviation 6.04	33 score on a scale Standard Deviation 5.17

SECONDARY outcome

Timeframe: Pre-dose, 4-hour post dose

Population: One participant is missing from placebo, acamprosate, lovastatin, and minocycline conditions due to being unable to repeat list words back to experimenter (nonverbal). Baclofen and placebo are each additionally missing one participant who did not complete the pre-dose or post-dose task.

Four 10-item lists of unrelated words were presented orally to the examinee who was then required to immediately recall words presented, at both pre-dose and post-dose timepoints. The impact of drug was assessed by subtracting the number of words remembered post-dose from the number of words remembered pre-dose. Lower numbers indicate more words remembered post-dose; higher numbers indicate more words remembered pre-dose.

Outcome measures

Measure	Placebo n=25 Participants Placebo: placebo pill	Acamprosate n=15 Participants Acamprosate: two 666mg pills	Lovastatin n=28 Participants Lovastatin: two 20mg pills	Minocycline n=26 Participants Minocycline: two 135mg pills	Baclofen n=17 Participants Baclofen: one 30mg pill
Change From Pre-dose in the Repeatable Battery for the Assessment of Neuropsychological Status at 4 Hours Post Dose	-.20 number of words remembered Standard Deviation 4.23	-1.47 number of words remembered Standard Deviation 5.17	-1.25 number of words remembered Standard Deviation 3.85	-.69 number of words remembered Standard Deviation 5.58	-.88 number of words remembered Standard Deviation 3.35

SECONDARY outcome

Timeframe: Predose, 4-hour post-dose

Population: One participant is missing from the placebo, acamprosate, lovastatin, and minocycline conditions due to being unable to participate in the task. An additional one participant each is missing from placebo, acamprosate, and lovastatin conditions due to uncollected data at either the pre-dose or post-dose timepoint.

Computerized task where an examinee is required to push a key when a target stimulus is presented on the screen. Scores are presented as change in median reaction time (RT), in milliseconds.

Outcome measures

Measure	Placebo n=25 Participants Placebo: placebo pill	Acamprosate n=14 Participants Acamprosate: two 666mg pills	Lovastatin n=27 Participants Lovastatin: two 20mg pills	Minocycline n=26 Participants Minocycline: two 135mg pills	Baclofen n=18 Participants Baclofen: one 30mg pill
Test of Attentional Performance for Children (KiTAP) Test of Alertness	13.76 change in median RT in milliseconds Standard Deviation 188.37	-28.64 change in median RT in milliseconds Standard Deviation 137.21	18.59 change in median RT in milliseconds Standard Deviation 169.39	26.85 change in median RT in milliseconds Standard Deviation 226.69	-31.44 change in median RT in milliseconds Standard Deviation 171.91

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Acamprosate

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Lovastatin

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Minocycline

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Baclofen

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=27 participants at risk Placebo: placebo pill	Acamprosate n=16 participants at risk Acamprosate: two 666mg pills	Lovastatin n=29 participants at risk Lovastatin: two 20mg pills	Minocycline n=27 participants at risk Minocycline: two 135mg pills	Baclofen n=18 participants at risk Baclofen: one 30mg pill
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	0.00% 0/27 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	12.5% 2/16 • Number of events 2 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/29 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/27 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/18 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.
Gastrointestinal disorders Nausea	0.00% 0/27 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/16 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/29 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/27 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	5.6% 1/18 • Number of events 1 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.
Gastrointestinal disorders Stomach pain	3.7% 1/27 • Number of events 1 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	6.2% 1/16 • Number of events 1 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	3.4% 1/29 • Number of events 1 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	7.4% 2/27 • Number of events 2 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/18 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.
Nervous system disorders Headache	0.00% 0/27 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	18.8% 3/16 • Number of events 3 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/29 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	11.1% 3/27 • Number of events 3 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/18 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.
Nervous system disorders Somnolence	3.7% 1/27 • Number of events 1 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	6.2% 1/16 • Number of events 1 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	3.4% 1/29 • Number of events 1 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/27 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/18 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.
Gastrointestinal disorders Diarrhea	0.00% 0/27 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	6.2% 1/16 • Number of events 1 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	3.4% 1/29 • Number of events 1 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	3.7% 1/27 • Number of events 1 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/18 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.
Psychiatric disorders Irritability	0.00% 0/27 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	6.2% 1/16 • Number of events 1 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	3.4% 1/29 • Number of events 1 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/27 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	11.1% 2/18 • Number of events 2 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.
Psychiatric disorders Confusion	0.00% 0/27 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	6.2% 1/16 • Number of events 1 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/29 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/27 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/18 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.
Eye disorders Blurred vision	0.00% 0/27 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	6.2% 1/16 • Number of events 1 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/29 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/27 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/18 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.
Psychiatric disorders Mania	7.4% 2/27 • Number of events 2 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/16 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	3.4% 1/29 • Number of events 1 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/27 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	5.6% 1/18 • Number of events 1 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.
Respiratory, thoracic and mediastinal disorders Sore throat	0.00% 0/27 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/16 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/29 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/27 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	5.6% 1/18 • Number of events 1 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/27 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/16 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/29 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	0.00% 0/27 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.	5.6% 1/18 • Number of events 1 • Adverse events were collected up to four weeks after the final dosing visit. Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.

Additional Information

Dr. Craig Erickson

Cincinnati Children's Hospital Medical Center

Phone: 513-636-0523

Email: craig.erickson@cchmc.org

Results disclosure agreements

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