Clinical trial NCT01304316: Dose-Escalation Safety and Pharmacokinetic Study of K305
Official title: Cardiovascular Changes and Tetracaine Pharmacokinetics Following Intranasal Administration of Standard and High Doses of Kovacaine Mist (Tetracaine Hydrochloride With Oxymetazoline Hydrochloride) in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anesthesia
Lead sponsor: St. Renatus, LLC
Sponsor class: INDUSTRY
Collaborators: name: Ground Zero Pharmaceuticals
name: Rho, Inc.
First posted: 2011-02-25
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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).

Eligibility criteria: 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

Primary outcomes:
measure: Cmax of Oxymetazoline
timeFrame: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes
measure: Cmax of Tetracaine
timeFrame: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes
measure: Cmax of PBBA
timeFrame: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes
measure: Half Life of Oxymetazoline
timeFrame: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes
measure: Half Life of Tetracaine
timeFrame: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes
measure: Half Life of PBBA
timeFrame: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes
Secondary outcomes:
measure: Pulse Oximetry Maximum Change From Baseline
timeFrame: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes
measure: Diastolic BP Maximum Change From Baseline
timeFrame: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes
measure: Systolic BP Maximum Change From Baseline
timeFrame: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes
measure: Pulse Rate Maximum Change From Baseline
timeFrame: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania, School of Dental Medicine
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Elliot V Hersh, DMD, MS, PhD
role: PRINCIPAL_INVESTIGATOR
References: