Dose-Escalation Safety and Pharmacokinetic Study of K305

Phase 2

Completed

Conditions: Anesthesia

Interventions: Drug: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%

Registration Number: NCT01304316

Lead Sponsor: St. Renatus, LLC

Brief 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

Detailed Description: The purpose of this study was to determine the safety and pharmacokinetics of the standard dose of intranasal Kovacaine Mist of 0.6 mL (18 mg tetracaine HCl with 0.3 mg oxymetazoline HCl) and a proposed maximum recommended dental dose of 1.2 mL (36 mg tetracaine HCl with 0.6 mg oxymetazoline HCl). The primary objectives were to determine if either dose significantly changed blood pressure readings (systolic and diastolic), pulse rate, or oxygen saturation levels from baseline pretreatment values and to determine the safety profile of both doses. The secondary objectives were to establish the pharmacokinetics of oxymetazoline, tetracaine, and its major metabolite (parabutylaminobenzoic acid) following the intranasal administration of both doses. Each subject received the standard dose (3 sprays in each nostril with 4 minutes between each pair of sprays) followed 1 to 3 weeks later by the high dose (as 6 sprays in each nostril).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 12

Inclusion Criteria

Male or female between 18 and 65 years of age
BMI between19 and 29 kg/m2
Sufficiently healthy as determined by the investigator to receive the test medications and undergo the scheduled study procedure
Can breathe through both nostrils
Females of child-bearing potential must have a negative urine pregnancy test and must have been using adequate means of birth control for at least one month prior to study entry and during the study
Screening BP ≤ 140/90
Screening SpO2 ≥ 96
Can understand and sign the informed consent document
Can communicate with the investigator
Can understand and comply with the requirements of the protocol.

Exclusion Criteria

A clinically relevant history or presence of respiratory, thyroid, gastrointestinal, renal, hepatic, hematological, lymphatic, cardiovascular, psychiatric, neurologic, musculoskeletal, genitourinary, infective, inflammatory, immunological, dermatological, or connective tissue disease or disorder or a clinically relevant history or presence of narrow angle glaucoma and in men benign prostatic hypertrophy, Hashimoto"s Thyroiditis, lymphocytic thyroiditis, or uncontrolled diabetes
Clinically significant abnormalities in laboratory values
Clinically relevant sinus/nasal surgical history
Current condition, such as nasal congestion or sinus infection, that may influence responses to study medication
History of recurrent nose bleeds
History of pseudocholinesterase deficiency or previous prolonged paralysis with succinylcholine or "difficulty waking up from general anesthesia"
Allergic to or intolerant of tetracaine, benzocaine, other ester local anesthetics, or para-aminobenzoic acid (as found in PABA-containing sunscreens)
Allergic to or intolerant of oxymetazoline or preservatives found in these solutions
History of alcoholism and/or drug abuse
Have taken a monamine oxidase inhibitor, or vasopressor drug within the past 3 weeks
Have received or taken local anesthetics within 72 hours of the first or second treatment visits
Are nursing, pregnant, suspected of being pregnant, or trying to become pregnant (Females will be required to take a urine pregnancy test at each study visit to rule out pregnancy)
Have used any investigational drug and/or participated in any clinical trial within 30 days of baseline

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Kovacaine Nasal Spray	Tetracaine HCl 3% and Oxymetazoline HCl 0.05%	Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: 6 sprays of 0.1 mL - total of 18 mg tetracaine HCl and 0.3 mg oxymetazoline HCl followed by 12 sprays of 0.1 mL - total of 36 mg tetracaine HCl and 0.6 mg oxymetazoline HCl

Primary Outcome Measures

Name	Time	Method
Cmax of PBBA	Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes	Extra-vascular, non-compartmental analysis is used to derive pharmacokinetic parameters; estimated from observed plasma concentration values, the dose administered, the AUCs, and the terminal elimination phase rate constant for each dose group
Cmax of Oxymetazoline	Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes	Extra-vascular, non-compartmental analysis is used to derive pharmacokinetic parameters; estimated from observed plasma concentration values, the dose administered, the AUCs, and the terminal elimination phase rate constant for each dose group
Half Life of PBBA	Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes	Extra-vascular, non-compartmental analysis is used to derive pharmacokinetic parameters; estimated from observed plasma concentration values, the dose administered, the AUCs, and the terminal elimination phase rate constant for each dose group
Cmax of Tetracaine	Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes	Extra-vascular, non-compartmental analysis is used to derive pharmacokinetic parameters; estimated from observed plasma concentration values, the dose administered, the AUCs, and the terminal elimination phase rate constant for each dose group
Half Life of Oxymetazoline	Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes	Extra-vascular, non-compartmental analysis is used to derive pharmacokinetic parameters; estimated from observed plasma concentration values, the dose administered, the AUCs, and the terminal elimination phase rate constant for each dose group
Half Life of Tetracaine	Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes	Extra-vascular, non-compartmental analysis is used to derive pharmacokinetic parameters; estimated from observed plasma concentration values, the dose administered, the AUCs, and the terminal elimination phase rate constant for each dose group

Secondary Outcome Measures

Name	Time	Method
Systolic BP Maximum Change From Baseline	Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes
Pulse Oximetry Maximum Change From Baseline	Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes
Diastolic BP Maximum Change From Baseline	Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes
Pulse Rate Maximum Change From Baseline	Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes