Evaluation of Viloxazine and Its Metabolite 5-Hydroxy-viloxazine Glucuronide Into Breast Milk in Healthy Lactating Women

Evaluation of the Excretion of Viloxazine and Its Metabolite 5-Hydroxy-viloxazine Glucuronide Into Breast Milk Following Multiple Doses of SPN-812 (600mg, QD) in Healthy Lactating Women

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06259331

Acronym

SPN-812

Enrollment

Registered

2024-02-14

Start date

2023-05-23

Completion date

2023-09-20

Last updated

2024-06-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy Lactating Women

Keywords

Healthy Lactating Women, Healthy Pregnancy

Brief summary

This is an open label, single treatment, multiple doses lactation study of SPN-812 in healthy lactating women. The study is designed to assess the excretion of viloxazine and its major metabolite 5-HVLX-gluc into breast milk following repeated administration of SPN-812 600 mg, QD. This study is comprised of Screening, Inpatient Admission, Treatment Period and End of Study (EOS). The total duration of the study is up to 32 days including Screening up to 28 days and 4 days of Treatment Period. Subjects will remain in the inpatient unit for 5 days, including the day of admission to the inpatient unit (Day -1), 3 days of dosing SM (Days 1-3), and the day of discharge (Day 4).

Detailed description

This is an open label, single treatment, multiple doses, lactation study of SPN-812 at steady state in healthy lactating women. The study is designed to assess the excretion of viloxazine and its major metabolite 5-HVLX-gluc into breast milk following repeated administration of SPN-812 600 mg daily for 3 days. The study is designed to assess the excretion of viloxazine and its major metabolite 5-HVLX-gluc into breast milk following repeated administration of SPN-812 600 mg, QD. This study is comprised of Screening, Inpatient Admission, Treatment Period, End of Study (EOS) with FU phone call. The total duration of the study is up to 32 days including Screening up to 28 days and 4 days of Treatment Period. Subjects will remain in the inpatient unit for 5 days, including the day of admission to the inpatient unit (Day -1), 3 days of dosing SM (Days 1-3), and the day of discharge (Day 4). Subjects will complete the screening visit, after informed consent is obtained, within 28 days prior to dose initiation. Inclusion/exclusion criteria will be reviewed to determine the subject's eligibility at Screening. A lactation consultant will be available to provide lactation support to subjects once they are enrolled. Since the mother's infant cannot receive breast milk for 7 consecutive days (Day-1 to Day 6), the mother will be reminded at Screening to make plans to have their infant fed 7 consecutive days with either (a) formula or (b) stored breast milk (e.g., breast milk pumped and stored in the freezer during the screening period between the screening visit and the day of admission to inpatient unit). Subjects will be admitted to the inpatient unit on Day -1 to confirm eligibility. Subjects will receive 600 mg SPN-812 in the morning of Days 1, 2 and 3 after completion of safety assessments. SM should be administered at the same time in the morning (±30 min) of dosing days. Breast milk and blood sample for PK analysis will then be collected on Day 3 per schedule. Non-PK breast milk expressed on Days -1, 1, and 2 will be collected over the time intervals and these samples will not be analyzed for drug concentrations. The volume and the start and end times of the collection of each non-PK and PK breast milk sample will be recorded. The end of study (EOS) procedures will be conducted prior to discharge on Day 4 following the last breast milk and blood sample collection. If subject discontinues early, all EOS procedures will be conducted.

Interventions

DRUGSPN-812 (600mg, QD)

Viloxazine ER

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to 45 Years

Healthy volunteers

Yes

Inclusion criteria

1. Healthy lactating females, 18 to 45 years of age, who are actively breastfeeding (including baby to breast, bottle feeding mother's expressed breast milk) and are at least 12 weeks postpartum of a healthy term newborn infant (no medical complications) and not more than 2 years postpartum. Lactation must be well established and the mother is exclusively breast feeding her baby (not providing supplemental formula) prior to the day of admission to inpatient unit. 2. Has a body mass index between 18 to 35 kg/m2, included. 3. Is considered medically healthy by the Investigator via assessment of physical examination (neurological examinations included), medical history, clinical laboratory tests, vital signs, Columbia-Suicide Severity Rating Scale (C-SSRS) and electrocardiogram (ECG). 4. Is willing to temporarily discontinue breastfeeding their infant and discard all their breast milk for 7 consecutive days, including day of admission to inpatient unit (Day -1), 3 consecutive days of dosing SM while in the inpatient unit (Days 1 to 3), and 3 consecutive days after last dose of SM (including day of discharge from the inpatient unit and 2 days at home; Days 4 to 6); and willing to store sufficient amount of breast milk (e.g., breast milk pumped and stored in freezer before the day of admission), and/or infant formula to feed infant during these 7 consecutive days. 5. Is either sexually inactive (abstinent) or, if sexually active, must agree to use/practice one of the following acceptable birth control methods beginning during the screening period prior to the first dose of SM, throughout the inpatient study, and for 3 days following the last dose of SM (Day 3): * intra-uterine contraceptive device; * barrier method: condom with spermicidal foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; * is surgically sterile or male partner is surgically sterile; * established use of a patch, vaginal ring, oral, injected or implanted hormonal methods of contraception that can be used in lactating women; * Essure® procedure performed at least 6 months prior to Screening and had hysterosalpingogram after the Essure procedure to document tubal occlusion prior to screening. 6. Must not be in the process of weaning before admission and have maintained an adequate breast milk supply with regularly pumping or routine breastfeeding (e.g., pumping or feeding 3-4 times a day) at admission. 7. Is currently a non-smoker who has not used tobacco or nicotine-containing products (chewed or smoked) or replacement products, including electronic cigarettes, within 3 months prior to screening and a negative cotinine test result at Screening. 8. Agrees to use only the emollient or nipple cream recommended by the investigator for use during the sampling period, if needed. 9. Able to voluntarily provide written informed consent to participate in the study. 10. Able to understand and willing to comply with all study requirements. 11. Able and willing to swallow capsules whole, without crushing, chewing, or cutting.

Exclusion criteria

1. Participation in any other investigational study drug trial in which receipt of an investigational study drug within 30 days or 5 half-lives before Screening, whichever is longer. 2. Is unwilling or unable to comply with the Lifestyle guidelines presented in the protocol during the study period. 3. Has history or presence of clinically significant systemic disease (including psychological and psychiatric disorders). 4. Is currently using, or tests positive at Screening for cotinine, alcohol, or drugs (opiates, methadone, cocaine, amphetamines \[including ecstasy\], barbiturates, PCP, benzodiazepines, and THC/cannabis). 5. Is pregnant (has positive serum pregnancy test at Screening) or becomes pregnant during study (has positive urine pregnancy test). 6. Has history of breast implants, breast augmentation, or breast reduction surgery. 7. Has history of mastitis within 30 days, breast cancer and/or has had a mastectomy or lumpectomy with the exception of a benign fibroma or lipoma removal at the investigator's discretion; and/or a clinically significant abnormality observed in either breast during a clinical breast exam at Screening or Admission (Day -1). 8. Has a history of alcohol use disorder within 1 year of Screening; or assessed by the PI as having regularly consumed alcohol exceeding 14 units per week (1 unit equals 340 mL of beer, 115 mL of wine, or 43 mL of spirits) within 1 year of Screening. 9. Is using recreational or illicit drug(s) (e.g., cannabis /tetrahydrocannabinol (THC), opiates, methadone, cocaine, amphetamines \[including ecstasy\], barbiturates, and benzodiazepines) within 1 year of Screening. 10. Has clinically significant vital signs abnormalities (systolic blood pressure less than 90 or greater than 140 mmHg, diastolic blood pressure less than 60 or greater than 90 mmHg, or pulse rate (PR) less than 50 or greater than 100 bpm at Screening. 11. Has a clinical laboratory test values outside the reference range at Screening that, in the opinion of the investigator, are clinically significant, or any of the following: * Serum creatinine \>1.5 times the upper limit of normal (ULN) * Serum total bilirubin \>1.5 times ULN * Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2 times ULN 12. Has clinically significant ECG abnormalities at Screening, including: * PR interval \>220 ms * QRS interval \>130 ms * QTcF interval \>470 ms 13. Has any disease or medication that could, in the investigator's opinion, interfere with the assessments of safety, tolerability, or interfere with the conduct or interpretation of the study. 14. Has evidence of infection with hepatitis B and C, and human immunodeficiency virus HIV-1 and HIV-2, as determined by results of testing at Screening. 15. Has a condition or planned procedure that may interfere with the absorption, metabolism, or elimination of the study drug (e.g., cholecystectomy). 16. Is using prescription medication within 14 days prior to administration of SM or 5 half-lives, whichever is longer, with the exception of hormonal contraceptives. 17. Is using over-the-counter products (including vitamins, herbal products and natural food supplements) within 14 days prior to administration of SM or 5 half-lives, whichever is longer. Exceptions include postnatal vitamins, topical products without systemic absorption and acetaminophen (\< 2 g/day). 18. Has an allergy to viloxazine. 19. Has an Edinburgh Postnatal Depression Scale score \>13. 20. Has attempted suicide within the 6 months prior to Screening or is at significant risk of suicide (either in the opinion of the Investigator or defined as a yes to suicidal ideation questions 4 or 5 or answering yes to suicidal behavior on the Columbia-Suicide Severity Rating Scale (C-SSRS) within the 12 months prior to screening). 21. In the investigator's opinion, is unlikely to comply with the protocol or is unsuitable for any other reason.

Design outcomes

Primary

Measure	Time frame	Description
AUCtau,Milk	Day 3: -4 to <0 hours pre-dose, and '0 to 4', '4 to 6', '6 to 8', '8 to 10', '10 to 12', '12 to 16' and '16 to 24' hours post-dose.	Area under the concentration-time curve over a 24-hour dosing interval in breast milk for viloxazine and its metabolite 5-HVLX-gluc
Cmax,Milk	-4 to <0 hours pre-dose, and '0 to 4', '4 to 6', '6 to 8', '8 to 10', '10 to 12', '12 to 16' and '16 to 24' hours post-dose.	Maximum observed concentration in breast milk for viloxazine and its metabolite 5-HVLX-gluc
Tmax,Milk	Day 3: -4 to <0 hours pre-dose, and '0 to 4', '4 to 6', '6 to 8', '8 to 10', '10 to 12', '12 to 16' and '16 to 24' hours post-dose.	time of maximum observed concentration in breast milk for viloxazine and its metabolite 5-HVLX-gluc
Ctrough,Milk	Day 3: -4 to <0 hours pre-dose, and '0 to 4', '4 to 6', '6 to 8', '8 to 10', '10 to 12', '12 to 16' and '16 to 24' hours post-dose.	Observed drug concentration in milk immediately before the next dose for viloxazine and its metabolite 5-HVLX-gluc
Cave,Milk	Day 3: -4 to <0 hours pre-dose, and '0 to 4', '4 to 6', '6 to 8', '8 to 10', '10 to 12', '12 to 16' and '16 to 24' hours post-dose.	Average drug concentration in milk, calculated as the ratio of AUCtau,milk/24 for viloxazine and its metabolite 5-HVLX-gluc

Secondary

Measure	Time frame	Description
Plasma Ctrough,ss	Day 3 pre-dose, and Day 3 at 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 16.0 and 24.0-hours post-dose.	Observed plasma concentration immediately before the next dose
Breast Milk-plasma Ratio (ML/PL)	Breast Milk PK Day 3: -4 to <0 hrs pre-dose, and '0 to 4', '4 to 6', '6 to 8', '8 to 10', '10 to 12', '12 to 16' and '16 to 24' hrs post-dose, Plasma PK Day 3 pre-dose, and Day 3 at 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 16.0 and 24.0-hrs post-dose	Breast milk-plasma ratio (ML/PL) based on AUC over 24 hours for viloxazine and 5-HVLX-gluc at plasma steady-state. Ratio of AUCtau from milk to AUCtau from plasma (CV%)
Estimated Daily Infant Dosage (EDID, mg/kg/Day)	Breast Milk PK Day 3: -4 to <0 hrs pre-dose, and '0 to 4', '4 to 6', '6 to 8', '8 to 10', '10 to 12', '12 to 16' and '16 to 24' hrs post-dose, Plasma PK Day 3 pre-dose, and Day 3 at 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 16.0 and 24.0-hrs post-dose	Estimated daily infant dosage (mg/kg/day) calculated as Milk/Plasma Ratio x the average maternal plasma concentration (Cave,ss) multiplied by 150 mL/kg/day (EDID 150) and 200 mL/kg/day (EDID 200), respectively.
Plasma AUCtau,ss	Day 3 pre-dose, and Day 3 at 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 16.0 and 24.0-hours post-dose.	Area under the concentration-time curve over the dosing interval (AUCtau) in plasma for viloxazine and its metabolite 5-HVLX-gluc at steady-state
Daily Infant Dosage (DID)	Breast Milk PK Day 3: -4 to <0 hrs pre-dose, and '0 to 4', '4 to 6', '6 to 8', '8 to 10', '10 to 12', '12 to 16' and '16 to 24' hrs post-dose, Plasma PK Day 3 pre-dose, and Day 3 at 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 16.0 and 24.0-hrs post-dose	Daily infant dosage (mg/day); total drug present in breast milk and consumed by the infant per day, which is equal to AM,milk.
Number of Participants With Adverse Events (AEs)	11 days	All subjects who are enrolled and who receive SM will be monitored and questioned regarding the occurrence of AEs. Adverse events occurring prior to SM administration on Study Day 1 will become part of the subject's medical history. Throughout the study, the Investigator must seek information on AEs by specific questioning and, as appropriate, by examination.
Relative Infant Dose (RID, %) at Plasma Steady-state	Breast Milk PK Day 3: -4 to <0 hrs pre-dose, and '0 to 4', '4 to 6', '6 to 8', '8 to 10', '10 to 12', '12 to 16' and '16 to 24' hrs post-dose, Plasma PK Day 3 pre-dose, and Day 3 at 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 16.0 and 24.0-hrs post-dose	Relative infant dose (%); the percent of the weight-adjusted maternal dosage consumed in breast milk over 24 hours, calculated as EDID (mg/kg/day)/maternal dosage (mg/kg/day) multiplied by 100 %.
Plasma Cmax,ss,	Day 3 pre-dose, and Day 3 at 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 16.0 and 24.0-hours post-dose.	Maximum observed concentration in plasma for viloxazine and its metabolite 5-HVLX-gluc
Plasma Tmax,ss	Day 3 pre-dose, and Day 3 at 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 16.0 and 24.0-hours post-dose.	Time to Peak Concentration
Plasma CL/Fss,	Day 3 pre-dose, and Day 3 at 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 16.0 and 24.0-hours post-dose.	Apparent clearance (Dose/AUCtau,ss)
Plasma Cave,ss	Day 3 pre-dose, and Day 3 at 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 16.0 and 24.0-hours post-dose.	Average plasma concentration, calculated as the ratio of AUCtau,ss/24

Countries

United States

Participant flow

Participants by arm

Arm	Count
Cohort 1 Up to 15 healthy, lactating women will be enrolled in the study. SPN-812 (600mg, QD):	15
Total	15

Baseline characteristics

Characteristic	Cohort 1
Age, Continuous	32.5 Years STANDARD_DEVIATION 4.16
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Pre-dose Metabolite concentration in Breast Milk	0.0 µg/mL STANDARD_DEVIATION 0
Pre-dose Metabolite Concentrations in Plasma	0.0 µg/mL STANDARD_DEVIATION 0
Pre-dose Viloxazine concentration in Breast milk	0.0 µg/mL STANDARD_DEVIATION 0
Pre-dose Viloxazine Concentrations in Plasma	0.0 µg/mL STANDARD_DEVIATION 0
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	4 Participants
Race (NIH/OMB) Black or African American	2 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	9 Participants
Region of Enrollment United States	15 participants
Sex: Female, Male Female	15 Participants
Sex: Female, Male Male	0 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 15
other Total, other adverse events	12 / 15
serious Total, serious adverse events	0 / 15

Outcome results

Primary

AUCtau,Milk

Area under the concentration-time curve over a 24-hour dosing interval in breast milk for viloxazine and its metabolite 5-HVLX-gluc

Time frame: Day 3: -4 to <0 hours pre-dose, and '0 to 4', '4 to 6', '6 to 8', '8 to 10', '10 to 12', '12 to 16' and '16 to 24' hours post-dose.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1	AUCtau,Milk	Viloxazine	21.4 µg•h/mL, (CV%)	Geometric Coefficient of Variation 34.4
Cohort 1	AUCtau,Milk	5-HVLX-gluc	1.59 µg•h/mL, (CV%)	Geometric Coefficient of Variation 31.1

Primary

Cave,Milk

Average drug concentration in milk, calculated as the ratio of AUCtau,milk/24 for viloxazine and its metabolite 5-HVLX-gluc

Time frame: Day 3: -4 to <0 hours pre-dose, and '0 to 4', '4 to 6', '6 to 8', '8 to 10', '10 to 12', '12 to 16' and '16 to 24' hours post-dose.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1	Cave,Milk	Viloxazine	0.912 µg/mL (CV%)	Geometric Coefficient of Variation 34.3
Cohort 1	Cave,Milk	5-HVLX-gluc	0.0677 µg/mL (CV%)	Geometric Coefficient of Variation 30.7

Primary

Cmax,Milk

Maximum observed concentration in breast milk for viloxazine and its metabolite 5-HVLX-gluc

Time frame: -4 to <0 hours pre-dose, and '0 to 4', '4 to 6', '6 to 8', '8 to 10', '10 to 12', '12 to 16' and '16 to 24' hours post-dose.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1	Cmax,Milk	Viloxazine	1.41 µg/mL, (CV%)	Geometric Coefficient of Variation 33.1
Cohort 1	Cmax,Milk	5-HVLX-gluc	0.0940 µg/mL, (CV%)	Geometric Coefficient of Variation 31.1

Primary

Ctrough,Milk

Observed drug concentration in milk immediately before the next dose for viloxazine and its metabolite 5-HVLX-gluc

Time frame: Day 3: -4 to <0 hours pre-dose, and '0 to 4', '4 to 6', '6 to 8', '8 to 10', '10 to 12', '12 to 16' and '16 to 24' hours post-dose.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1	Ctrough,Milk	Viloxazine	0.426 µg/mL (CV%)	Geometric Coefficient of Variation 48.4
Cohort 1	Ctrough,Milk	5-HVLX-gluc	0.0480 µg/mL (CV%)	Geometric Coefficient of Variation 33.3

Primary

Tmax,Milk

time of maximum observed concentration in breast milk for viloxazine and its metabolite 5-HVLX-gluc

Time frame: Day 3: -4 to <0 hours pre-dose, and '0 to 4', '4 to 6', '6 to 8', '8 to 10', '10 to 12', '12 to 16' and '16 to 24' hours post-dose.

Arm	Measure	Group	Value (MEDIAN)
Cohort 1	Tmax,Milk	Viloxazine	5.53 h (min to max)
Cohort 1	Tmax,Milk	5-HVLX-gluc	9.53 h (min to max)

Secondary

Breast Milk-plasma Ratio (ML/PL)

Breast milk-plasma ratio (ML/PL) based on AUC over 24 hours for viloxazine and 5-HVLX-gluc at plasma steady-state. Ratio of AUCtau from milk to AUCtau from plasma (CV%)

Time frame: Breast Milk PK Day 3: -4 to <0 hrs pre-dose, and '0 to 4', '4 to 6', '6 to 8', '8 to 10', '10 to 12', '12 to 16' and '16 to 24' hrs post-dose, Plasma PK Day 3 pre-dose, and Day 3 at 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 16.0 and 24.0-hrs post-dose

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1	Breast Milk-plasma Ratio (ML/PL)	Viloxazine	0.338 Ratio (CV%)	Geometric Coefficient of Variation 17.4
Cohort 1	Breast Milk-plasma Ratio (ML/PL)	5-HVLX-gluc	0.0376 Ratio (CV%)	Geometric Coefficient of Variation 28.4

Secondary

Daily Infant Dosage (DID)

Daily infant dosage (mg/day); total drug present in breast milk and consumed by the infant per day, which is equal to AM,milk.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1	Daily Infant Dosage (DID)	Viloxazine	0.511 mg/day (CV%)	Geometric Coefficient of Variation 69.8
Cohort 1	Daily Infant Dosage (DID)	5-HVLX-gluc	0.0357 mg/day (CV%)	Geometric Coefficient of Variation 48.2

Secondary

Estimated Daily Infant Dosage (EDID, mg/kg/Day)

Estimated daily infant dosage (mg/kg/day) calculated as Milk/Plasma Ratio x the average maternal plasma concentration (Cave,ss) multiplied by 150 mL/kg/day (EDID 150) and 200 mL/kg/day (EDID 200), respectively.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1	Estimated Daily Infant Dosage (EDID, mg/kg/Day)	Viloxazine EDID 150	0.134 mg/kg/Day (CV%)	Geometric Coefficient of Variation 34.4
Cohort 1	Estimated Daily Infant Dosage (EDID, mg/kg/Day)	5-HVLX-gluc EDID 150	0.00994 mg/kg/Day (CV%)	Geometric Coefficient of Variation 31.1
Cohort 1	Estimated Daily Infant Dosage (EDID, mg/kg/Day)	Viloxazine EDID 200	0.178 mg/kg/Day (CV%)	Geometric Coefficient of Variation 34.4
Cohort 1	Estimated Daily Infant Dosage (EDID, mg/kg/Day)	5-HVLX-gluc EDID 200	0.0133 mg/kg/Day (CV%)	Geometric Coefficient of Variation 31.1

Secondary

Number of Participants With Adverse Events (AEs)

All subjects who are enrolled and who receive SM will be monitored and questioned regarding the occurrence of AEs. Adverse events occurring prior to SM administration on Study Day 1 will become part of the subject's medical history. Throughout the study, the Investigator must seek information on AEs by specific questioning and, as appropriate, by examination.

Time frame: 11 days

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cohort 1	Number of Participants With Adverse Events (AEs)	12 Participants

Secondary

Plasma AUCtau,ss

Area under the concentration-time curve over the dosing interval (AUCtau) in plasma for viloxazine and its metabolite 5-HVLX-gluc at steady-state