Safety and Pharmacokinetics of Kovacaine Nasal Spray (24 Hour Blood Collection)

Anesthesia Clinical Trial

Official title:

The Pharmacokinetics Of Tetracaine, Para-Butylaminobenzoic Acid, And Oxymetazoline After Intranasal Administration Of The Highest Phase 3 Dose Of Kovacaine™ Mist To Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01807624
• Other study ID #: SR 2-06
• Status: Completed
• Phase: Phase 2
• First received: March 5, 2013
• Last updated: May 15, 2015
• Start date: March 2013
• Est. completion date: March 2013

Study information

• Verified date: May 2015
• Source: St. Renatus, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the pharmacokinetics/pharmacodynamics and safety of a nasal spray containing the anesthetic drug tetracaine in combination with oxymetazoline with blood draws over 24 hours.

Description:

The purpose of this study is to determine the pharmacokinetics and safety of tetracaine, para- butylaminobenzoic acid (PBBA), and oxymetazoline after intranasal administration of the highest Phase 3 dose of Kovacaine Mist (Tetracaine Hydrochloride with Oxymetazoline Hydrochloride) to healthy volunteers.

This is an open-label, single-treatment, single-dose study in healthy volunteers in which all subjects will receive the highest Phase 3 dose of Kovacaine Mist on one occasion. No randomization is necessary for this single treatment, single dose study. A single study center will participate.

Each subject will receive a single dose of Kovacaine Mist (3% tetracaine HCl with 0.05% oxymetazoline HCl) consisting of 3 sprays (each 0.2 mL) in one nostril not taking longer than 8 minutes, for a total 0.6 mL dose containing 18 mg tetracaine HCl and 0.3 mg oxymetazoline HCl.

The total dosing period will be 8 minutes. Subjects will be required to fast 10 hours prior to dosing and for four (4) hours after dosing. Water will be allowed ad lib during the study except for one (1) hour prior through one (1) hour after dose administration. Subjects will be admitted to the study unit no later than 2100 hours of the evening prior to drug administration and will remain in the unit until the 24 hour blood sample is collected and discharge procedures are completed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Male or non-pregnant, non-breast-feeding female subjects between the ages of 18 and 75 years (inclusive).

• Can understand and sign the informed consent document, can communicate with the investigator, and can understand and comply with the requirements of the protocol.

• Body mass index between 18 and 35 BMI.

• Sufficiently healthy as determined by the investigator to receive the test medications and undergo the scheduled study procedure.

• Can breathe through both nostrils.

• Screening BP = 140/90 mm Hg.

Exclusion Criteria:

• History of clinically significant respiratory, gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular disease, including cardiac arrhythmia, narrow angle glaucoma and benign prostatic hypertrophy (in men), uncontrolled thyroid disease (including Hashimoto's Thyroiditis and lymphocytic thyroiditis), uncontrolled diabetes mellitus or any other condition which, in the opinion of the Principal Investigator, would jeopardize the safety of the subject or impact the validity of the study results.

• Has clinically significant abnormal findings on the physical examination, medical history, electrocardiogram (ECG), or clinical laboratory evaluation during screening. This includes current upper respiratory infections.

• Currently experiencing seasonal or perennial allergic rhinitis, recurrent nose-bleeds or asthma, or has a significant history of these conditions, in the opinion of the Investigator.

• Current, including the last 30 days, sinusitis or other upper respiratory infections.

• Nasal polyps, significant nasal or sinus surgery or other abnormality that may interfere with the dose administration.

• History of allergic or adverse responses to tetracaine, other ester local anesthetics, PBBA, oxymetazoline and its preservatives, or para-aminobenzoic acid as found in PABA containing sunscreens or any comparable or similar product.

• Donation of blood or plasma within 30 days of the first dose of Study Drug.

• Participation in a clinical trial within 30 days prior to the first dose of Study Drug.

• Use of any new over-the-counter (OTC) medication, including topical anesthetic creams or gels, vitamins, within seven days prior to the first dose of the Study Drug or during the study unless approved by the Principal Investigator.

• Any prescription medication, whose dose is not stable at the time of screening, as determined by the Principal Investigator.

• Treatment with any known enzyme altering drugs such as barbiturates, phenothiazines, cimetidine, carbamazepine, etc., within 30 days prior to the first dose of Study Drug or during the study.

• Smoking or use of tobacco products within 6 months prior to the first dose of Study Drug or during the study.

• Female trying to conceive, is pregnant, suspected of being pregnant, or is lactating. (Females of child-bearing potential will be required to take a serum pregnancy test at screening (up to 21 days prior to the start of the study, including the day of the study), as well as a urine pregnancy test at check-in to rule out pregnancy.)

• Positive serum pregnancy test at screening or urine pregnancy test at check-in for all women of childbearing potential.

• Positive blood screen for HIV, Hepatitis B surface antigen (HbSAg), or Hepatitis C, or a positive urine screen for alcohol, drugs of abuse, or cotinine.

• Have a history of pseudocholinesterase deficiency or previous prolonged paralysis with succinylcholine or difficulty waking up from general anesthesia.

• Have a history of alcoholism and/or drug abuse.

• Have taken a monoamine oxidase inhibitor or vasopressor drug within the past 3 weeks.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anesthesia

Intervention

Drug:
• Tetracaine HCl 3% and Oxymetazoline HCl 0.05%
1 spray is 0.2mL is volume and contains 6mg Tetracaine HCl 3% and 0.1mg Oxymetazoline HCl

Locations

Country	Name	City	State
United States	Jean Brown Research	Salt Lake City	Utah

Sponsors (4)

Lead Sponsor	Collaborator
St. Renatus, LLC	Analytical Bio-Chemistry Laboratories, Inc., Rho, Inc., Triligent International

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak Plasma Concentration (Cmax) of tetracaine		0, 5, 10, 15, 20, 25, 30, 40, 50 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 16 and 24 hours after completion of the last nasal spray	No
Primary	Time to Peak Plasma Concentration (Cmax) of tetracaine		0, 5, 10, 15, 20, 25, 30, 40, 50 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 16 and 24 hours after completion of the last nasal spray	No
Primary	Terminal elimination rate constant (?z) of tetracaine		0, 5, 10, 15, 20, 25, 30, 40, 50 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 16 and 24 hours after completion of the last nasal spray	No
Primary	Elimination half-life (t½) of tetracaine		0, 5, 10, 15, 20, 25, 30, 40, 50 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 16 and 24 hours after completion of the last nasal spray	No
Primary	Area under the plasma concentration versus time curve (AUC) of tetracaine		0, 5, 10, 15, 20, 25, 30, 40, 50 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 16 and 24 hours after completion of the last nasal spray	No
Primary	Peak Plasma Concentration (Cmax) of para- butylaminobenzoic acid (PBBA)		0, 5, 10, 15, 20, 25, 30, 40, 50 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 16 and 24 hours after completion of the last nasal spray	No
Primary	Time to Peak Plasma Concentration (Cmax) of para- butylaminobenzoic acid (PBBA)		0, 5, 10, 15, 20, 25, 30, 40, 50 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 16 and 24 hours after completion of the last nasal spray	No
Primary	Terminal elimination rate constant (?z) of para- butylaminobenzoic acid (PBBA)		0, 5, 10, 15, 20, 25, 30, 40, 50 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 16 and 24 hours after completion of the last nasal spray	No
Primary	Elimination half-life (t½) of para- butylaminobenzoic acid (PBBA)		0, 5, 10, 15, 20, 25, 30, 40, 50 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 16 and 24 hours after completion of the last nasal spray	No
Primary	Area under the plasma concentration versus time curve (AUC) of para- butylaminobenzoic acid (PBBA)		0, 5, 10, 15, 20, 25, 30, 40, 50 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 16 and 24 hours after completion of the last nasal spray	No
Primary	Peak Plasma Concentration (Cmax) of oxymetazoline		0, 5, 10, 15, 20, 25, 30, 40, 50 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 16 and 24 hours after completion of the last nasal spray	No
Primary	Time to Peak Plasma Concentration (Cmax) of oxymetazoline		0, 5, 10, 15, 20, 25, 30, 40, 50 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 16 and 24 hours after completion of the last nasal spray	No
Primary	Terminal elimination rate constant (?z) of oxymetazoline		0, 5, 10, 15, 20, 25, 30, 40, 50 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 16 and 24 hours after completion of the last nasal spray	No
Primary	Elimination half-life (t½) of oxymetazoline		0, 5, 10, 15, 20, 25, 30, 40, 50 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 16 and 24 hours after completion of the last nasal spray	No
Primary	Area under the plasma concentration versus time curve (AUC) of oxymetazoline		0, 5, 10, 15, 20, 25, 30, 40, 50 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 16 and 24 hours after completion of the last nasal spray	No
Secondary	Mean and Standard Deviation of Heart Rate		0, 5, 10, 15, 20, 25, 30, 40, 50 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 16 and 24 hours after completion of the last nasal spray	Yes
Secondary	Mean and Standard Deviation of Systolic Blood Pressure		0, 5, 10, 15, 20, 25, 30, 40, 50 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 16 and 24 hours after completion of the last nasal spray	Yes
Secondary	Mean and Standard Deviation of Diastolic Blood Pressure		0, 5, 10, 15, 20, 25, 30, 40, 50 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 16 and 24 hours after completion of the last nasal spray	Yes
Secondary	Mean and Standard Deviation of Temperature		0, 5, 10, 15, 20, 25, 30, 40, 50 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 16 and 24 hours after completion of the last nasal spray	Yes
Secondary	Mean and Standard Deviation of Oxygen Saturation		0, 5, 10, 15, 20, 25, 30, 40, 50 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 16 and 24 hours after completion of the last nasal spray	Yes