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

NCT06259331 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 812P418
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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).

Conditions

Healthy Lactating Women

Keywords

Healthy Lactating Women; Healthy Pregnancy

Outcome Measures

Primary Outcomes (5)

• 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

  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.

• Cmax,Milk

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

  -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.

• Tmax,Milk

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

  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.

• Ctrough,Milk

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

  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.

• Cave,Milk

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

  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.

Secondary Outcomes (11)

• 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.

• 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.

• 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.

• 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.

• 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.

Study Arms (1)

Cohort 1

EXPERIMENTAL

Up to 15 healthy, lactating women will be enrolled in the study.

Drug: SPN-812 (600mg, QD)

Interventions

SPN-812 (600mg, QD) DRUG

Viloxazine ER

Cohort 1

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Has a body mass index between 18 to 35 kg/m2, included.
• 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).
• 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.
• 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.
• 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.
• 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.
• Agrees to use only the emollient or nipple cream recommended by the investigator for use during the sampling period, if needed.
• Able to voluntarily provide written informed consent to participate in the study.
• Able to understand and willing to comply with all study requirements.

You may not qualify if:

• 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.
• Is unwilling or unable to comply with the Lifestyle guidelines presented in the protocol during the study period.
• Has history or presence of clinically significant systemic disease (including psychological and psychiatric disorders).
• 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).
• Is pregnant (has positive serum pregnancy test at Screening) or becomes pregnant during study (has positive urine pregnancy test).
• Has history of breast implants, breast augmentation, or breast reduction surgery.
• 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).
• 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.
• 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.
• 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.
• 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
• Has clinically significant ECG abnormalities at Screening, including:

Sponsors & Collaborators

• Supernus Pharmaceuticals, Inc.: lead

Study Sites (1)

PPD Phase I Clinic

Las Vegas, Nevada, 89113, United States

Location

Results Point of Contact

• Title: Charlene A. Tucker
• Organization: Supernus

ctucker@supernus.com

(301) 838-2500

Study Officials

• Ying Cai

  Clinical Pharmacology

  STUDY DIRECTOR

• Darin B Brimhall, DO

  PPD Phase I Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2024
• First Posted: February 14, 2024
• Study Start: May 23, 2023
• Primary Completion: September 20, 2023
• Study Completion: September 20, 2023
• Last Updated: June 6, 2024
• Results First Posted: June 6, 2024

Record last verified: 2024-06

Locations

US (1)