Trial Outcomes & Findings for 28-Day Daily-dose Crossover Study of the Safety and Tolerability of SB-121 (Lactobacillus Reuteri With Sephadex® and Maltose) in Subjects, Ages 15 to 45 Years, Diagnosed With Autistic Disorder (NCT NCT04944901)

Last Updated: 2024-03-25

Results Overview

Adverse event of special interest (AESIs) and adverse events (AEs) leading to discontinuation from the study are presented. Treatment Period 1: 2 participants reported 4 events in the SB-121 group and 3 participant reported 6 events in the placebo group. Treatment Period 2: 1 participant reported 3 events in the SB-121 group and 1 participant reported 4 events in the placebo group.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

15 participants

Primary outcome timeframe

Approximately 98 days

Results posted on

2024-03-25

Participant Flow

A total of 15 participants were randomized in this crossover study.

Participant milestones

Participant milestones
Measure	Group 1 (SB-121 - Placebo) Treatment Period 1: One oral dose of SB-121 daily for 28 days. Treatment Period 2: One oral dose of placebo daily for 28 days. SB-121: SB-121 is a formulation of L. reuteri	Group 2 (Placebo - SB-121) Treatment Period 1: One dose of oral placebo daily for 28 days. Treatment Period 2: One oral dose of SB-121 daily for 28 days. SB-121: SB-121 is a formulation of L. reuteri
Treatment Period 1 STARTED	7	8
Treatment Period 1 COMPLETED	7	8
Treatment Period 1 NOT COMPLETED	0	0
Treatment Period 2 STARTED	7	8
Treatment Period 2 COMPLETED	7	8
Treatment Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

28-Day Daily-dose Crossover Study of the Safety and Tolerability of SB-121 (Lactobacillus Reuteri With Sephadex® and Maltose) in Subjects, Ages 15 to 45 Years, Diagnosed With Autistic Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1 (SB-121 - Placebo) n=7 Participants Treatment Period 1: One oral dose of SB-121 daily for 28 days. Treatment Period 2: One oral dose of placebo daily for 28 days. SB-121: SB-121 is a formulation of L. reuteri	Group 2 (Placebo - SB-121) n=8 Participants Treatment Period 1: One dose of oral placebo daily for 28 days. Treatment Period 2: One oral dose of SB-121 daily for 28 days. SB-121: SB-121 is a formulation of L. reuteri	Total n=15 Participants Total of all reporting groups
Age, Continuous	20.1 years STANDARD_DEVIATION 1.46 • n=5 Participants	19.9 years STANDARD_DEVIATION 4.09 • n=7 Participants	20.0 years STANDARD_DEVIATION 3.05 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Race/Ethnicity, Customized White	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment United States	7 participants n=5 Participants	8 participants n=7 Participants	15 participants n=5 Participants
Height	177.96 centimeters STANDARD_DEVIATION 6.904 • n=5 Participants	178.54 centimeters STANDARD_DEVIATION 6.280 • n=7 Participants	178.27 centimeters STANDARD_DEVIATION 6.343 • n=5 Participants
Weight	69.67 kilograms STANDARD_DEVIATION 9.725 • n=5 Participants	98.26 kilograms STANDARD_DEVIATION 40.006 • n=7 Participants	84.92 kilograms STANDARD_DEVIATION 32.538 • n=5 Participants
Body mass index	22.11 kilogram/meter squared STANDARD_DEVIATION 3.859 • n=5 Participants	31.29 kilogram/meter squared STANDARD_DEVIATION 14.552 • n=7 Participants	27.01 kilogram/meter squared STANDARD_DEVIATION 11.606 • n=5 Participants
Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) Score	16.0 ADOS-2 Score STANDARD_DEVIATION 4.40 • n=5 Participants	13.6 ADOS-2 Score STANDARD_DEVIATION 3.02 • n=7 Participants	14.7 ADOS-2 Score STANDARD_DEVIATION 3.79 • n=5 Participants
Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5 checklist) Met criteria for Autism Spectrum Disorder	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5 checklist) Not met criteria for Autism Spectrum Disorder	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Drug Abuse Screen via Urine Negative	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Drug Abuse Screen via Urine Positive	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Approximately 98 days

Population: Safety Population

Outcome measures

Outcome measures
Measure	SB-121 n=15 Participants One dose of SB-121 daily for 28 days according to the treatment group to which they are allocated. Administration: Oral SB-121: SB-121 is a formulation of L. reuteri	Placebo n=15 Participants One dose of placebo daily for 28 days according to the treatment group to which they are allocated. Administration: Oral Placebo: Placebo oral formulation
Adverse Event of Special Interest (AESIs) and Adverse Events (AEs) Leading to Discontinuation Treatment Period 2 : Vomiting (AESI)	0 adverse events	1 adverse events
Adverse Event of Special Interest (AESIs) and Adverse Events (AEs) Leading to Discontinuation Treatment Period 1 : Abdominal pain upper (AESI)	2 adverse events	0 adverse events
Adverse Event of Special Interest (AESIs) and Adverse Events (AEs) Leading to Discontinuation Treatment Period 1 : Adverse events leading to discontinuation	0 adverse events	0 adverse events
Adverse Event of Special Interest (AESIs) and Adverse Events (AEs) Leading to Discontinuation Treatment Period 1 : Diarrhoea (AESI)	1 adverse events	2 adverse events
Adverse Event of Special Interest (AESIs) and Adverse Events (AEs) Leading to Discontinuation Treatment Period 1 : Abdominal pain (AESI)	0 adverse events	2 adverse events
Adverse Event of Special Interest (AESIs) and Adverse Events (AEs) Leading to Discontinuation Treatment Period 1 : Nausea (AESI)	1 adverse events	0 adverse events
Adverse Event of Special Interest (AESIs) and Adverse Events (AEs) Leading to Discontinuation Treatment Period 1 : Vomiting (AESI)	0 adverse events	2 adverse events
Adverse Event of Special Interest (AESIs) and Adverse Events (AEs) Leading to Discontinuation Treatment Period 2 : Adverse events leading to discontinuation	0 adverse events	0 adverse events
Adverse Event of Special Interest (AESIs) and Adverse Events (AEs) Leading to Discontinuation Treatment Period 2 : Diarrhoea (AESI)	3 adverse events	3 adverse events
Adverse Event of Special Interest (AESIs) and Adverse Events (AEs) Leading to Discontinuation Treatment Period 2 : Abdominal pain (AESI)	0 adverse events	0 adverse events
Adverse Event of Special Interest (AESIs) and Adverse Events (AEs) Leading to Discontinuation Treatment Period 2 : Abdominal pain upper (AESI)	0 adverse events	0 adverse events
Adverse Event of Special Interest (AESIs) and Adverse Events (AEs) Leading to Discontinuation Treatment Period 2 : Nausea (AESI)	0 adverse events	0 adverse events

PRIMARY outcome

Timeframe: Period 1: Days 1 (pre-dose), 28 and 35; Period 2: Days 28 and 42 (period = 28 days and 14 days wash-out)

Population: Intent-to-Treat Population

The presence of Sephadex microspheres in the stool was assessed. The number of participants with data available at each stage are presented.

Outcome measures

Outcome measures
Measure	SB-121 n=15 Participants One dose of SB-121 daily for 28 days according to the treatment group to which they are allocated. Administration: Oral SB-121: SB-121 is a formulation of L. reuteri	Placebo n=15 Participants One dose of placebo daily for 28 days according to the treatment group to which they are allocated. Administration: Oral Placebo: Placebo oral formulation
Sephadex Microspheres in the Stool Period 1 Day 28 · Sephadex Positive	6 Participants	5 Participants
Sephadex Microspheres in the Stool Period 1 Day 1 · Sephadex Positive	2 Participants	1 Participants
Sephadex Microspheres in the Stool Period 1 Day 1 · Sephadex Negative	1 Participants	2 Participants
Sephadex Microspheres in the Stool Period 1 Day 28 · Sephadex Negative	0 Participants	0 Participants
Sephadex Microspheres in the Stool Period 1 Day 35/Washout · Sephadex Positive	2 Participants	2 Participants
Sephadex Microspheres in the Stool Period 1 Day 35/Washout · Sephadex Negative	1 Participants	2 Participants
Sephadex Microspheres in the Stool Period 2 Day 28/End of treatment · Sephadex Positive	4 Participants	1 Participants
Sephadex Microspheres in the Stool Period 2 Day 28/End of treatment · Sephadex Negative	0 Participants	0 Participants
Sephadex Microspheres in the Stool Period 2 Day 42/Poststudy Washout · Sephadex Positive	0 Participants	1 Participants
Sephadex Microspheres in the Stool Period 2 Day 42/Poststudy Washout · Sephadex Negative	3 Participants	2 Participants

PRIMARY outcome

Timeframe: Approximately 98 days

Population: Intent-to-Treat Population

The presence of symptomatic bacteremia with positive L. reuteri identification was assessed and none of the participants in either group showed any clinical features of suspected bacteremia in this study.

Outcome measures

Outcome measures
Measure	SB-121 n=15 Participants One dose of SB-121 daily for 28 days according to the treatment group to which they are allocated. Administration: Oral SB-121: SB-121 is a formulation of L. reuteri	Placebo n=15 Participants One dose of placebo daily for 28 days according to the treatment group to which they are allocated. Administration: Oral Placebo: Placebo oral formulation
Symptomatic Bacteremia With Positive L. Reuteri Identification	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day -28 to Day 0, Period 1: Day 28; Period 2: Days 1 (pre-dose) and 28 (period = 28 days and 14 days wash-out)

Population: Safety Population. To be noted changes at crossover in N: Treatment Period 1 - SB-121 (N=7) and Placebo (N=8) Treatment Period 2 - SB-121 (N=8) and Placebo (N=7)

Mean (standard deviation) percent changes from baseline in tumor necrosis factor-α

Outcome measures

Outcome measures
Measure	SB-121 n=15 Participants One dose of SB-121 daily for 28 days according to the treatment group to which they are allocated. Administration: Oral SB-121: SB-121 is a formulation of L. reuteri	Placebo n=15 Participants One dose of placebo daily for 28 days according to the treatment group to which they are allocated. Administration: Oral Placebo: Placebo oral formulation
Mean Percent Change From Baseline in Biomarkers: Tumor Necrosis Factor-α changes from baseline to Treatment Period 2 (Day 28/end of treatment)	-1.11 percentage Standard Deviation 16.51	8.77 percentage Standard Deviation 50.41
Mean Percent Change From Baseline in Biomarkers: Tumor Necrosis Factor-α changes from baseline to Treatment Period 1 (Day 28)	37.98 percentage Standard Deviation 57.70	0.27 percentage Standard Deviation 23.23

SECONDARY outcome

Timeframe: Day -28 to Day 0, Period 1: Day 28; Period 2: Days 1 (pre-dose) and 28 (period = 28 days and 14 days wash-out)

Population: Safety Population. To be noted changes at crossover in N: Treatment Period 1 - SB-121 (N=7) and Placebo (N=8) Treatment Period 2 - SB-121 (N=8) and Placebo (N=7)

Mean (standard deviation) percent change from baseline in serum high-sensitivity C-reactive protein (hs-CRP)

Outcome measures

Outcome measures
Measure	SB-121 n=15 Participants One dose of SB-121 daily for 28 days according to the treatment group to which they are allocated. Administration: Oral SB-121: SB-121 is a formulation of L. reuteri	Placebo n=15 Participants One dose of placebo daily for 28 days according to the treatment group to which they are allocated. Administration: Oral Placebo: Placebo oral formulation
Mean Percent Change From Baseline in Biomarkers: Serum High-sensitivity C-reactive Protein (Hs-CRP) changes from baseline to Treatment Period 2 (Day 28/end of treatment)	-13.91 percent Standard Deviation 40.56	-33.13 percent Standard Deviation 30.52
Mean Percent Change From Baseline in Biomarkers: Serum High-sensitivity C-reactive Protein (Hs-CRP) changes from baseline to Treatment Period 1 (Day 28)	173.38 percent Standard Deviation 306.88	45.70 percent Standard Deviation 118.29

SECONDARY outcome

Timeframe: Period 1: Days 1 (pre-dose), 28 and 35; Period 2: Days 28 and 35 (period = 28 days and 14 days wash-out)

Population: Safety Population. To be noted changes at crossover in N: Treatment Period 1 - SB-121 (N=7) and Placebo (N=8) Treatment Period 2 - SB-121 (N=8) and Placebo (N=7)

Mean (standard deviation) percent change from baseline in stool biomarkers, fecal calprotectin. The number of participants with data available are presented.

Outcome measures

Outcome measures
Measure	SB-121 n=15 Participants One dose of SB-121 daily for 28 days according to the treatment group to which they are allocated. Administration: Oral SB-121: SB-121 is a formulation of L. reuteri	Placebo n=15 Participants One dose of placebo daily for 28 days according to the treatment group to which they are allocated. Administration: Oral Placebo: Placebo oral formulation
Mean Percent Change From Baseline in Biomarkers: Stool Biomarkers, Fecal Calprotectin changes from baseline to Treatment Period 1 (Day 28)	76.1 percent Standard Deviation 99.79	2.7 percent Standard Deviation 67.29
Mean Percent Change From Baseline in Biomarkers: Stool Biomarkers, Fecal Calprotectin changes from baseline Treatment Period 2 (Day 28/end of treatment)	-39.9 percent Standard Deviation 25.21	-26.1 percent Standard Deviation 21.78
Mean Percent Change From Baseline in Biomarkers: Stool Biomarkers, Fecal Calprotectin changes from baseline Treatment Period 2 (Day 42/poststudy washout)	-4.2 percent Standard Deviation 35.56	-14.0 percent Standard Deviation 25.43

SECONDARY outcome

Timeframe: Period 1: Days 1 (pre-dose), 28 and 35; Period 2: Days 28 and 35 (period = 28 days and 14 days wash-out)

Population: Safety Population. To be noted changes at crossover in N: Treatment Period 1 - SB-121 (N=7) and Placebo (N=8) Treatment Period 2 - SB-121 (N=8) and Placebo (N=7)

Mean (standard deviation) percent change from baseline in stool biomarkers, fecal lactoferrin. The number of participants with data available are presented.

Outcome measures

Outcome measures
Measure	SB-121 n=15 Participants One dose of SB-121 daily for 28 days according to the treatment group to which they are allocated. Administration: Oral SB-121: SB-121 is a formulation of L. reuteri	Placebo n=15 Participants One dose of placebo daily for 28 days according to the treatment group to which they are allocated. Administration: Oral Placebo: Placebo oral formulation
Mean Percent Change From Baseline in Biomarkers: Stool Biomarkers, Fecal Lactoferrin change from baseline to Treatment Period 1 (Day 28)	NA percent Standard Deviation NA NA = 0.0. The reason these values are "0" is a combination of: 1) There were a lot stool samples missing so most do not have both pre and post sample values, and 2) values below the LLQ parameter are reported as 1.000 which was the case for most samples.	49.40 percent Standard Deviation 110.46
Mean Percent Change From Baseline in Biomarkers: Stool Biomarkers, Fecal Lactoferrin change from baseline to Treatment Period 2 (Day 28/end of treatment)	12.33 percent Standard Deviation 36.63	-42.90 percent Standard Deviation 35.75
Mean Percent Change From Baseline in Biomarkers: Stool Biomarkers, Fecal Lactoferrin change from baseline to Treatment Period 2 (Day 42/poststudy washout)	47.08 percent Standard Deviation 105.57	-40.97 percent Standard Deviation 34.52

SECONDARY outcome

Timeframe: Day -28 to Day 0, Period 1: Day 28; Period 2: Days 1 and 28 (period = 28 days and 14 days wash-out)

Population: Safety Population To be noted changes at crossover in N: Treatment Period 1 - SB-121 (N=7) and Placebo (N=8) Treatment Period 2 - SB-121 (N=8) and Placebo (N=7)

The mean (standard deviation) percent changes from baseline in plasma oxytocin.

Outcome measures

Outcome measures
Measure	SB-121 n=15 Participants One dose of SB-121 daily for 28 days according to the treatment group to which they are allocated. Administration: Oral SB-121: SB-121 is a formulation of L. reuteri	Placebo n=15 Participants One dose of placebo daily for 28 days according to the treatment group to which they are allocated. Administration: Oral Placebo: Placebo oral formulation
Mean Percent Change From Baseline in Biomarkers: Plasma Oxytocin change from baseline to Treatment Period 1 (Day 28)	178.83 percent Standard Deviation 167.54	61.69 percent Standard Deviation 95.04
Mean Percent Change From Baseline in Biomarkers: Plasma Oxytocin change from baseline to Treatment Period 2 (Day 28/end of treatment)	44.43 percent Standard Deviation 118.64	-18.53 percent Standard Deviation 26.92

SECONDARY outcome

Timeframe: Day -28 to Day 0, Period 1: Day 28; Period 2: Days 1 (pre-dose) and 28 (period = 28 days and 14 days wash-out)

Population: Safety Population To be noted changes at crossover in N: Treatment Period 1 - SB-121 (N=7) and Placebo (N=8) Treatment Period 2 - SB-121 (N=8) and Placebo (N=7)

Mean (standard deviation) percent changes from baseline in plasma vasopressin levels

Outcome measures

Outcome measures
Measure	SB-121 n=15 Participants One dose of SB-121 daily for 28 days according to the treatment group to which they are allocated. Administration: Oral SB-121: SB-121 is a formulation of L. reuteri	Placebo n=15 Participants One dose of placebo daily for 28 days according to the treatment group to which they are allocated. Administration: Oral Placebo: Placebo oral formulation
Mean Percent Change From Baseline in Biomarkers: Plasma Vasopressin change from baseline to Treatment Period 1 (Day 28)	55.98 percent Standard Deviation 115.43	16.53 percent Standard Deviation 41.70
Mean Percent Change From Baseline in Biomarkers: Plasma Vasopressin change from baseline to Treatment Period 2 (Day 28/end of treatment)	-10.14 percent Standard Deviation 27.80	21.36 percent Standard Deviation 72.46

Adverse Events

SB-121

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Phoevos Hughes, VP Clinical Operations

Scioto Biosciences

Phone: 866-672-4686

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	SB-121 n=15 participants at risk Includes all participants who received SB-121, whether in Treatment Period 1 or 2.	Placebo n=15 participants at risk Includes all participants who received placebo, whether in Treatment Period 1 or 2.
Blood and lymphatic system disorders Leukocytosis	6.7% 1/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	0.00% 0/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.
Gastrointestinal disorders Diarrhoea	13.3% 2/15 • Number of events 4 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	20.0% 3/15 • Number of events 5 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.
Gastrointestinal disorders Abdominal pain upper	6.7% 1/15 • Number of events 2 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	0.00% 0/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.
Gastrointestinal disorders Nausea	6.7% 1/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	0.00% 0/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.
Gastrointestinal disorders Vomiting	0.00% 0/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	13.3% 2/15 • Number of events 3 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.
Gastrointestinal disorders Abdominal pain	0.00% 0/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	6.7% 1/15 • Number of events 2 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.
General disorders Fatigue	6.7% 1/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	0.00% 0/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.
General disorders Pain	0.00% 0/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	6.7% 1/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.
Infections and infestations Sinusitis	13.3% 2/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	0.00% 0/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.
Infections and infestations COVID-19	0.00% 0/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	6.7% 1/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.
Infections and infestations Tinea infection	0.00% 0/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	6.7% 1/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.
Infections and infestations Upper respiratory tract infection	0.00% 0/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	6.7% 1/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.
Investigations Alanine aminotransferase increased	0.00% 0/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	6.7% 1/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.
Nervous system disorders Headache	6.7% 1/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	13.3% 2/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.
Psychiatric disorders Anxiety	0.00% 0/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	6.7% 1/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.
Psychiatric disorders Depression	0.00% 0/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	6.7% 1/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.
Psychiatric disorders Insomnia	0.00% 0/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	6.7% 1/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.
Renal and urinary disorders Bilirubinuria	0.00% 0/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	6.7% 1/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.
Respiratory, thoracic and mediastinal disorders Cough	13.3% 2/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	0.00% 0/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	6.7% 1/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.	6.7% 1/15 • Any time after informed consent was obtained until 14 days after study treatment, approximately 14 weeks (112 days) The study team recorded all adverse events (AEs) with start dates occurring any time after informed consent was obtained until 14 days after study treatment. At each study visit, the study team asked about the occurrence of AEs since the last visit whether in the clinic or on the phone.