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Trial Outcomes & Findings for Evaluation of Viloxazine and Its Metabolite 5-Hydroxy-viloxazine Glucuronide Into Breast Milk in Healthy Lactating Women (NCT NCT06259331)

NCT ID: NCT06259331

Last Updated: 2024-06-06

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

15 participants

Primary outcome timeframe

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.

Results posted on

2024-06-06

Participant Flow

Participant milestones

Participant milestones
Measure
Cohort 1
Up to 15 healthy, lactating women will be enrolled in the study. SPN-812 (600mg, QD): SPN-812 (600mg, QD)
Overall Study
STARTED
15
Overall Study
COMPLETED
15
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Cohort 1
n=15 Participants
Up to 15 healthy, lactating women will be enrolled in the study. SPN-812 (600mg, QD):
Age, Continuous
32.5 Years
STANDARD_DEVIATION 4.16 • n=99 Participants
Sex: Female, Male
Female
15 Participants
n=99 Participants
Sex: Female, Male
Male
0 Participants
n=99 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=99 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
15 Participants
n=99 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=99 Participants
Race (NIH/OMB)
Asian
4 Participants
n=99 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=99 Participants
Race (NIH/OMB)
Black or African American
2 Participants
n=99 Participants
Race (NIH/OMB)
White
9 Participants
n=99 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=99 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
Region of Enrollment
United States
15 participants
n=99 Participants
Pre-dose Viloxazine Concentrations in Plasma
0.0 µg/mL
STANDARD_DEVIATION 0.0 • n=99 Participants
Pre-dose Metabolite Concentrations in Plasma
0.0 µg/mL
STANDARD_DEVIATION 0.0 • n=99 Participants
Pre-dose Viloxazine concentration in Breast milk
0.0 µg/mL
STANDARD_DEVIATION 0.0 • n=99 Participants
Pre-dose Metabolite concentration in Breast Milk
0.0 µg/mL
STANDARD_DEVIATION 0.0 • n=99 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Cohort 1
n=15 Participants
Up to 15 healthy, lactating women will be enrolled in the study. SPN-812 (600mg, QD): SPN-812 (600mg, QD)
AUCtau,Milk
Viloxazine
21.4 µg•h/mL, (CV%)
Geometric Coefficient of Variation 34.4
AUCtau,Milk
5-HVLX-gluc
1.59 µg•h/mL, (CV%)
Geometric Coefficient of Variation 31.1

PRIMARY outcome

Timeframe: -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

Outcome measures

Outcome measures
Measure
Cohort 1
n=15 Participants
Up to 15 healthy, lactating women will be enrolled in the study. SPN-812 (600mg, QD): SPN-812 (600mg, QD)
Cmax,Milk
Viloxazine
1.41 µg/mL, (CV%)
Geometric Coefficient of Variation 33.1
Cmax,Milk
5-HVLX-gluc
0.0940 µg/mL, (CV%)
Geometric Coefficient of Variation 31.1

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Cohort 1
n=15 Participants
Up to 15 healthy, lactating women will be enrolled in the study. SPN-812 (600mg, QD): SPN-812 (600mg, QD)
Tmax,Milk
Viloxazine
5.53 h (min to max)
Interval 3.54 to 7.6
Tmax,Milk
5-HVLX-gluc
9.53 h (min to max)
Interval 5.63 to 15.59

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Cohort 1
n=15 Participants
Up to 15 healthy, lactating women will be enrolled in the study. SPN-812 (600mg, QD): SPN-812 (600mg, QD)
Ctrough,Milk
Viloxazine
0.426 µg/mL (CV%)
Geometric Coefficient of Variation 48.4
Ctrough,Milk
5-HVLX-gluc
0.0480 µg/mL (CV%)
Geometric Coefficient of Variation 33.3

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Cohort 1
n=15 Participants
Up to 15 healthy, lactating women will be enrolled in the study. SPN-812 (600mg, QD): SPN-812 (600mg, QD)
Cave,Milk
Viloxazine
0.912 µg/mL (CV%)
Geometric Coefficient of Variation 34.3
Cave,Milk
5-HVLX-gluc
0.0677 µg/mL (CV%)
Geometric Coefficient of Variation 30.7

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Cohort 1
n=15 Participants
Up to 15 healthy, lactating women will be enrolled in the study. SPN-812 (600mg, QD): SPN-812 (600mg, QD)
Plasma AUCtau,ss
Viloxazine
63.4 µg•h/mL, (CV%)
Geometric Coefficient of Variation 28.2
Plasma AUCtau,ss
5-HVLX-gluc
42.3 µg•h/mL, (CV%)
Geometric Coefficient of Variation 21.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Cohort 1
n=15 Participants
Up to 15 healthy, lactating women will be enrolled in the study. SPN-812 (600mg, QD): SPN-812 (600mg, QD)
Plasma Cmax,ss,
Viloxazine
3.92 µg/mL, (CV%)
Geometric Coefficient of Variation 23.7
Plasma Cmax,ss,
5-HVLX-gluc
2.73 µg/mL, (CV%)
Geometric Coefficient of Variation 19.3

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Cohort 1
n=15 Participants
Up to 15 healthy, lactating women will be enrolled in the study. SPN-812 (600mg, QD): SPN-812 (600mg, QD)
Plasma Tmax,ss
Viloxazine
5.00 h (min to max)
Interval 0.5 to 6.03
Plasma Tmax,ss
5-HVLX-gluc
6.00 h (min to max)
Interval 5.0 to 8.0

SECONDARY outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure
Cohort 1
n=15 Participants
Up to 15 healthy, lactating women will be enrolled in the study. SPN-812 (600mg, QD): SPN-812 (600mg, QD)
Plasma CL/Fss,
Viloxazine
9.46 L/h, (CV%)
Geometric Coefficient of Variation 28.2
Plasma CL/Fss,
5-HVLX-gluc
NA L/h, (CV%)
Geometric Coefficient of Variation NA
Not Calculated. From the mass balance study, it was identified that the major metabolite of viloxazine following oral SPN-812 (viloxazine) was 5-HVLX-gluc; however, the factor of in vivo conversion of viloxazine to 5-HVLX-gluc is not known. Therefore, the amount of 5-HVLX-gluc to estimate total clearance of 5-HVLX-gluc, i.e., the amount in equation to calculate the CL/Fss = (Amount of 5-HVLX-gluc/AUC of 5-HVLX-gluc) is not known and the CLss/F of 5-HVLX-gluc is not calculable.

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Cohort 1
n=15 Participants
Up to 15 healthy, lactating women will be enrolled in the study. SPN-812 (600mg, QD): SPN-812 (600mg, QD)
Plasma Cave,ss
Viloxazine
2.64 µg/mL, (CV%)
Geometric Coefficient of Variation 28.3
Plasma Cave,ss
5-HLVX-gluc
1.76 µg/mL, (CV%)
Geometric Coefficient of Variation 21.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Cohort 1
n=15 Participants
Up to 15 healthy, lactating women will be enrolled in the study. SPN-812 (600mg, QD): SPN-812 (600mg, QD)
Plasma Ctrough,ss
Viloxazine
1.36 µg/mL, (CV%)
Geometric Coefficient of Variation 46.7
Plasma Ctrough,ss
5-HVLX-gluc
0.878 µg/mL, (CV%)
Geometric Coefficient of Variation 27.3

SECONDARY outcome

Timeframe: 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%)

Outcome measures

Outcome measures
Measure
Cohort 1
n=15 Participants
Up to 15 healthy, lactating women will be enrolled in the study. SPN-812 (600mg, QD): SPN-812 (600mg, QD)
Breast Milk-plasma Ratio (ML/PL)
Viloxazine
0.338 Ratio (CV%)
Geometric Coefficient of Variation 17.4
Breast Milk-plasma Ratio (ML/PL)
5-HVLX-gluc
0.0376 Ratio (CV%)
Geometric Coefficient of Variation 28.4

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Cohort 1
n=15 Participants
Up to 15 healthy, lactating women will be enrolled in the study. SPN-812 (600mg, QD): SPN-812 (600mg, QD)
Estimated Daily Infant Dosage (EDID, mg/kg/Day)
Viloxazine EDID 150
0.134 mg/kg/Day (CV%)
Geometric Coefficient of Variation 34.4
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
Estimated Daily Infant Dosage (EDID, mg/kg/Day)
Viloxazine EDID 200
0.178 mg/kg/Day (CV%)
Geometric Coefficient of Variation 34.4
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 outcome

Timeframe: 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 %.

Outcome measures

Outcome measures
Measure
Cohort 1
n=15 Participants
Up to 15 healthy, lactating women will be enrolled in the study. SPN-812 (600mg, QD): SPN-812 (600mg, QD)
Relative Infant Dose (RID, %) at Plasma Steady-state
Viloxazine RID 150 (%) (based on EDID 150)
1.53 Percent (CV%)
Geometric Coefficient of Variation 27.6
Relative Infant Dose (RID, %) at Plasma Steady-state
5-HVLX-gluc 150 (%) (based on EDID 150)
0.114 Percent (CV%)
Geometric Coefficient of Variation 38.2
Relative Infant Dose (RID, %) at Plasma Steady-state
Viloxazine RID 200 (%) (based on EDID 200)
2.04 Percent (CV%)
Geometric Coefficient of Variation 27.6
Relative Infant Dose (RID, %) at Plasma Steady-state
5-HVLX-gluc 200 (%) (based on EDID 200)
0.152 Percent (CV%)
Geometric Coefficient of Variation 38.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Cohort 1
n=15 Participants
Up to 15 healthy, lactating women will be enrolled in the study. SPN-812 (600mg, QD): SPN-812 (600mg, QD)
Daily Infant Dosage (DID)
Viloxazine
0.511 mg/day (CV%)
Geometric Coefficient of Variation 69.8
Daily Infant Dosage (DID)
5-HVLX-gluc
0.0357 mg/day (CV%)
Geometric Coefficient of Variation 48.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Cohort 1
n=15 Participants
Up to 15 healthy, lactating women will be enrolled in the study. SPN-812 (600mg, QD): SPN-812 (600mg, QD)
Number of Participants With Adverse Events (AEs)
12 Participants

Adverse Events

Cohort 1

Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Cohort 1
n=15 participants at risk
Up to 15 healthy, lactating women will be enrolled in the study. SPN-812 (600mg, QD): SPN-812 (600mg, QD)
Nervous system disorders
somnolence
66.7%
10/15 • Number of events 10 • 11 days
Nervous system disorders
dizziness
20.0%
3/15 • Number of events 3 • 11 days
Gastrointestinal disorders
nausea
20.0%
3/15 • Number of events 3 • 11 days
Reproductive system and breast disorders
breast tenderness
20.0%
3/15 • Number of events 3 • 11 days
Nervous system disorders
headache
13.3%
2/15 • Number of events 2 • 11 days
Gastrointestinal disorders
dry mouth
13.3%
2/15 • Number of events 2 • 11 days
Metabolism and nutrition disorders
decreased appetite
6.7%
1/15 • Number of events 1 • 11 days
Gastrointestinal disorders
dyspepsia
6.7%
1/15 • Number of events 1 • 11 days
General disorders
chills
6.7%
1/15 • Number of events 1 • 11 days
Skin and subcutaneous tissue disorders
dermatitis
6.7%
1/15 • Number of events 1 • 11 days
Vascular disorders
hot flush
6.7%
1/15 • Number of events 1 • 11 days

Additional Information

Charlene A. Tucker

Supernus

Phone: (301) 838-2500

Results disclosure agreements

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