Clinical trial NCT04792034: Pharmacokinetics, Safety, and Tolerability Study of GOPRELTO® Nasal Solution
Official title: Open-label, Pharmacokinetics, Safety, and Tolerability Study of a Single Topical Dose of GOPRELTO® Nasal Solution for the Induction of Local Anesthesia in Pediatric Subjects From ≥12 Years to <17 Years of Age
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: ENT Disorder
Keywords: Nasal
Sinus
ENT
Lead sponsor: Pharmaceutical Project Solutions, Inc.
Sponsor class: INDUSTRY
First posted: 2021-03-10
Enrollment: 20
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open label
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the pharmacokinetic (PK) properties, safety, tolerability, and dosing of GOPRELTO® as an anesthetic for diagnostic procedures and surgeries on or through the mucous membranes of the nasal cavities in pediatric adolescent subjects.

Detailed description: GOPRELTO® (cocaine hydrochloride nasal solution, 4%) is an approved product in adults. The purpose of this study is to assess the pharmacokinetic (PK) properties, safety, tolerability, and dosing of GOPRELTO® as an anesthetic for diagnostic procedures and surgeries on or through the mucous membranes of the nasal cavities in pediatric adolescent subjects.

The primary objectives of the study are:

* To assess the safety and tolerability of GOPRELTO® nasal solution in pediatric adolescent subjects as an anesthetic for diagnostic procedures and surgeries on or through the mucous membranes of the nasal cavities.
* To evaluate the PK properties and define the dosing for GOPRELTO® nasal solution in pediatric adolescent subjects as an anesthetic for diagnostic procedures and surgeries on or through the mucous membranes of the nasal cavities.

Eligibility criteria: Inclusion Criteria:

A subject will be eligible for inclusion in the study if he or she meets all of the following criteria:

1. Is accompanied and/or represented by a parent or guardian able to comprehend and sign the informed consent document.
2. Is able to understand and provide assent to an age-appropriate subject assent form (as defined by local practice or regulation).
3. Subject or parent/guardian is able to communicate with the Investigator and comply with the requirements of the protocol.
4. Is male or female ≥12 to \<17 years of age at the time of dosing.
5. Is within the 10th and 90th percentiles for weight according to age.
6. Has a body mass index (BMI) within the 5th and 85th percentiles by age.
7. Has an oxygen saturation of at least 98%.
8. Will be undergoing a diagnostic procedure or surgery on or through the nasal mucous membranes of either one or both nostrils.
9. 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. 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.

Exclusion Criteria:

* Exclusion

A subject will be excluded from the study if he or she meets any of the following criteria:

1. Has a history of seizures.
2. Has a known hypersensitivity allergy to any ester-based anesthetics including cocaine hydrochloride, procaine, tetracaine, chloroprocaine, dibucaine, or benzocaine, and/or any other compounds of the drugs and /or devices that are part of this protocol (amide based anesthetics are NOT exclusionary).
3. Has previously received intranasal topical cocaine within 14 days prior to the Screening Visit.
4. Has participated in an investigational study or received an investigational drug within 30 days preceding Treatment Day 1.
5. Has a history of abuse of controlled substances, nasal or otherwise.
6. 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.
7. Is a pregnant female or nursing mother, or has a positive urine pregnancy test at the Screening Visit or on Treatment Day 1.
8. Use of any serotonin-norepinephrine reuptake inhibitors/selective serotonin reuptake inhibitor (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.
9. 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.
10. 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.
11. Use of disulfiram.
12. Planned or anticipated need for additional vasoconstrictor agents such as epinephrine or phenylephrine.
13. 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.
14. 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.
15. 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.
16. Has an ECG finding of any abnormality at the Screening Visit. Generally, these exclusionary abnormalities are current or prior myocardial ischemia or infarction, dysrhythmia, or risk of serious dysrhythmia (such as prolonged QT interval). An exception to this would be if sinus bradycardia or sinus tachycardia is present. The Investigator must determine whether this finding is clinically significant and exclusionary.
17. Has a known personal or family history of hereditary pseudocholinesterase deficiency.
18. Has a known or suspected personal or family history of pheochromocytoma. Study participants will be specifically asked if they have been treated for a pheochromocytoma previously or if they have a family member who has been diagnosed with pheochromocytoma (as 10% of these are familial).
19. Has any laboratory result outside the normal laboratory reference range deemed clinically significant by the Investigator.
20. Has a history of or current, hepatic, or renal disease.
21. Is not suitable for entry into the study, in the opinion of the Investigator. Note: A one-time retest is permitted for any blood test if the original sample was hemolyzed.

Primary outcomes:
measure: The number of patients who experience a rise or drop in blood pressure greater than or less than 150 bpm.
timeFrame: 24 Days
measure: Pharmacokinetic Measurements of Cocaine HCl Topical Solution to demonstrate the Cmax of Cocaine HCl Topical Solution blood levels over 9-10 hours.
timeFrame: 9-10 Hours
measure: Pharmacokinetic Measurements of Cocaine HCl Topical Solution to demonstrate the AUC of Cocaine HCl Topical Solution blood levels over 9-10 hours.
timeFrame: 9-10 Hours
measure: Heart Rate
timeFrame: 9-10 Hours
measure: Blood Pressure
timeFrame: 9-10 Hours
measure: Respiratory Rate
timeFrame: 9-10 Hours
measure: Electrocardiograms to Measure
timeFrame: 9-10 hours
measure: Electrocardiograms to Measure EEG Power in your Alpha Band
timeFrame: 9-10 hours
measure: Pulse Oximetry
timeFrame: 9-10 hours
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References: