Pharmacokinetics, Safety, and Tolerability Study of GOPRELTO® Nasal Solution and NUMBRINO™ Nasal Solution

NCT04792034 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: RA-VP-000-357
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to assess the pharmacokinetic (PK) properties, safety and tolerability following a single dose administration of GOPRELTO® or NUMBRINO™ as an anesthetic for diagnostic procedures and surgeries on or through the mucous membranes of the nasal cavities in pediatric adolescent subjects.

Conditions

Nasal Anesthesia; Nasal Mucosa Surgery; ENT Disorder; Nasal Procedures

Keywords

Nasal; Sinus; ENT

Outcome Measures

Primary Outcomes (13)

• Changes in Blood pressure

  Changes in blood pressure from baseline of 20 mmHg systolic or 15 mmHg diastolic OR when blood pressure reaches 150/90 mmHg in the automated blood pressure monitoring system during the mentioned time frame. Measurements will be taken in supine position with 3 measurements 5-6 minutes apart.

  Baseline and every 5 minutes through 90 minutes post-pledget application.

• Changes in Heart rate

  Increase in heart rate from baseline of 20 bpm OR when heart rate of 125 bpm is reached at any point in the automated vital sign monitoring system during the mentioned time frame.

  Baseline and every 5 minutes through 90 minutes post-pledget application.

• Changes in Respiratory Rate

  Any changes in respiratory rate (increase or decrease) while on study medication.

  Baseline and every 15 minutes through 90 minutes post-pledget application.

• Physical examination

  Assessment of skin, head, ears, eyes, nose, throat, neck, thyroid, lungs, heart, cardiovascular, abdomen, lymph nodes, and musculoskeletal system/extremities; oral temperature, height, weight; BMI as well as height and weight percentiles.

  Screening Visit

• Electrocardiogram

  Any changes or delays in heart rhythm while on medication. Electrocardiogram will be performed in the supine position.

  Screening Visit, and on Day 1 at Baseline (pre-dose), continuously during treatment, and through 90 minutes post-pledget application

• Pulse Oximetry

  Any changes in the amount of oxygen in the blood while on study medication.

  Screening Visit, and on Day 1 at Baseline (pre-dose), continuously during treatment, and through 90 minutes post-pledget application

• Incidence of Adverse events (AEs)

  The number and percentage of subjects with AEs, AEs severity, causality, Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs).

  From Day 1 (pledget application) through the final follow-up call at Day 10.

• Maximum observed plasma concentration (Cmax)

  Measurement of the amount of the study medication (cocaine topical solution) in the blood over 8 hours to define the Cmax.

  Screening Visit, Baseline (pre-dose), 20, 40, 60, and 90 minutes, and 2, 4, and 8 hours after pledget application.

• Time to maximum observed plasma concentration (Tmax)

  Measurement of the time it takes after dosing for the study medication (cocaine topical solution) to reach its highest observed concentration in the blood over 8 hours.

  Screening Visit, Baseline (pre-dose), 20, 40, 60, and 90 minutes, and 2, 4, and 8 hours after pledget application.

• Area under the plasma concentration versus time curve from time of dosing (0) to the time of last quantifiable concentration (AUClast)

  Measurement of the amount of the study medication (cocaine topical solution) in the blood over 8 hours to define the AUC.

  Screening Visit, Baseline (pre-dose), 20, 40, 60, and 90 minutes, and 2, 4, and 8 hours after pledget application.

• Area under the plasma concentration versus time curve from time of dosing (0) to infinity (AUCinf)

  Measurement of the total exposure to the study medication in the blood over 8 hours, starting from dosing and extrapolated to infinity.

  Screening Visit, Baseline (pre-dose), 20, 40, 60, and 90 minutes, and 2, 4, and 8 hours after pledget application.

• Terminal rate constant in plasma from the negative of the regression line slope through the ln plasma concentration versus time data defining the terminal phase [kel (λz)]

  Measurement of the time it takes for the concentration of the study medication in the blood to decrease by half during the terminal elimination phase, over 8 hours, calculated using kel as ln(2)/kel.

  Screening Visit, Baseline (pre-dose), 20, 40, 60, and 90 minutes, and 2, 4, and 8 hours after pledget application.

• Terminal half-life in plasma calculated from the kel as ln(2)/kel (t½)

  Measurement of the rate at which the study medication is eliminated from the blood during the terminal phase, calculated from the slope of the log-transformed concentration versus time data.

  Baseline (pre-dose), 20, 40, 60, and 90 minutes, and 2, 4, and 8 hours after pledget application.

Other Outcomes (4)

• Application Site Assessment

  Screening Visit, Day 1 before drug application (Baseline), and within 90 minutes following the completion of the procedure.

• Pediatric Smell Wheel

  Screening Visit and 90 minutes post-procedure on Day 1.

• Assessment of Analgesia and Anesthesia

  Screening Visit and on Day 1 (following pledget removal but prior to procedure).

Study Arms (2)

GOPRELTO® nasal solution, 4%,

EXPERIMENTAL

FDA Approved GOPRELTO® (cocaine hydrochloride nasal solution, 4%); Up to 160 mg depending on subject's weight; Saturated cottonoid pledgets are applied topically in both nostrils by study personnel

Drug: Cocaine Hydrochloride Nasal Solution

NUMBRINO™ nasal solution, 4%

EXPERIMENTAL

FDA Approved NUMBRINO™ (cocaine hydrochloride nasal solution, 4%); Up to 160 mg depending on subject's weight; Saturated cottonoid pledgets are applied topically in both nostrils by study personnel

Drug: Cocaine Hydrochloride Nasal Solution

Interventions

Cocaine Hydrochloride Nasal Solution DRUG

Topical Anesthetic

Also known as: GOPRELTO®

GOPRELTO® nasal solution, 4%,

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Is accompanied and/or represented by a parent or guardian able to comprehend and sign the informed consent document.
• Is able to understand and provide assent to an age-appropriate subject assent form (as defined by local practice or regulation).
• Subject or parent/guardian is able to communicate with the Investigator and comply with the requirements of the protocol.
• Is male or female ≥12 to \<18 years of age at the time of dosing.
• Is no lower than the 10th percentile for weight according to age.
• Has a body mass index (BMI) no lower than the 5th percentile by age.
• Has an oxygen saturation of at least 98%.
• Will be undergoing a diagnostic procedure or surgery on or through the nasal mucous membranes of either one or both nostrils.
• Is a non-pregnant, non-lactating female (if of child-bearing potential and sexually active) or is a male (if sexually active with a partner of child-bearing potential) who agrees to use a medically acceptable and effective birth control method from the time of the Screening Visit and then for 8 days following the last dose of GOPRELTO® nasal solution or NUMBRINO™ nasal solution administration. Medically acceptable methods of contraception that may be used by the participant and/or his/her partner include: abstinence, FDA-approved hormonal contraceptives (i.e., birth control pill, injection, patch or vaginal ring), diaphragm, intrauterine device, double-barrier methods, surgical sterilization, and progestin implant or injection. Prohibited methods include: the rhythm method or withdrawal.

You may not qualify if:

• A subject will be excluded from the study if he or she meets any of the following criteria:
• Has a history of seizure.
• Has previously received intranasal topical cocaine within 14 days prior to the Screening Visit.
• Has participated in an investigational study or received an investigational drug within 30 days preceding Treatment Day 1.
• Has a history of abuse of controlled substances, nasal or otherwise.
• Has a positive test result for drugs of abuse at the Screening Visit: amphetamines, barbiturates, cannabinoids, cocaine metabolites, opiates, and oxycodone via a urine test. Alcohol is prohibited within 24 hours prior to Treatment Day 1.
• Is a pregnant female or nursing mother or has a positive urine pregnancy test at the Screening Visit or on Treatment Day 1.
• Use of any serotonin-norepinephrine reuptake inhibitors/selective serotonin reuptake inhibitors (SNRIs/SSRIs) up to 14 days prior to the Screening Visit or has a need to use these drugs at any time throughout the duration of the study.
• Use of monoamine oxidase inhibitor (MAO) drugs up to 14 days prior to the Screening Visit or has a need to use these drugs at any time throughout the duration of the study.
• Use of nasal products such as decongestants (oxymetazoline, phenylephrine), amphetamines, stimulant prescription and nonprescription products such as catecholamines (direct and indirect-acting sympathomimetics), bronchial inhalers containing sympathomimetics (epinephrine or other beta-receptor agonists), or herbal products in the 2 days prior to the Screening Visit or has a need to use these drugs through or on Treatment Day 1.
• Use of disulfiram.
• Planned or anticipated need for additional vasoconstrictor agents such as epinephrine or phenylephrine.
• Suffers from a condition, other than the need for a diagnostic procedure or surgery on or through the nasal mucous membranes, which in the opinion of the Investigator, would compromise the safety of the subject, the quality of the data, or the normal wound healing process.
• Has severely traumatized mucosa or septum in the nasal cavities or has damage to the nasal space that will not allow pledgets to be inserted.
• Has a recent or active history of myocardial infarction, coronary artery disease, congestive heart failure, unstable angina, or uncontrolled hypertension. Uncontrolled hypertension is defined as systolic blood pressure or diastolic blood pressure greater than or equal to the 95th percentile by sex, age and height.

Sponsors & Collaborators

• Noden Pharma: lead
• Omnivium Pharmaceuticals LLC: collaborator
• LXO Group: collaborator

Study Sites (4)

SCENT Sleep and Allergy, 110 Highland Center Drive

Columbia, South Carolina, 29203, United States

RECRUITING

SCENT Sleep and Allergy, 145 Park Central

Columbia, South Carolina, 29203, United States

RECRUITING

South Carolina ENT, Sleep and Allergy

Columbia, South Carolina, 29212, United States

RECRUITING

SCENT Sleep and Allergy, 15 Exchange Dr.

Lugoff, South Carolina, 29078, United States

RECRUITING

MeSH Terms

Conditions

Fistula

Condition Hierarchy (Ancestors)

Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Robert Puchlaski, M.D

CONTACT

803-256-7076; 803-549-2467; rpuchalski@me.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, single-dose, non-randomized, two-arm sequential, single-center study

Study Record Dates

• First Submitted: February 22, 2021
• First Posted: March 10, 2021
• Study Start: December 6, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 26, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)