Dose-Escalation Safety and Pharmacokinetic Study of K305

• ClinicalTrials.gov Identifier: NCT01304316
• Recruitment Status: Completed
• First Posted: February 25, 2011
• Results First Posted: August 31, 2017
• Last Update Posted: August 31, 2017
• Sponsor: St. Renatus, LLC
• Collaborators: Ground Zero Pharmaceuticals; Rho, Inc.
• Information provided by (Responsible Party): St. Renatus, LLC

Study Description

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

Condition or disease	Intervention/treatment	Phase
Anesthesia	Drug: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%	Phase 2

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• 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 Start Date: September 2010
• Actual Primary Completion Date: November 2010
• Actual Study Completion Date: November 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Kovacaine Nasal Spray; 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	Drug: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%; Tetracaine HCl 3% and Oxymetazoline HCl 0.05%; Other Name: Kovacaine Nasal Spray

Outcome Measures

Primary Outcome Measures :

1. Cmax of Oxymetazoline [ Time Frame: 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
2. Cmax of Tetracaine [ Time Frame: 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
3. Cmax of PBBA [ Time Frame: 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
4. Half Life of Oxymetazoline [ Time Frame: 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
5. Half Life of Tetracaine [ Time Frame: 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
6. Half Life of PBBA [ Time Frame: 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 :

1. Pulse Oximetry Maximum Change From Baseline [ Time Frame: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes ]
2. Diastolic BP Maximum Change From Baseline [ Time Frame: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes ]
3. Systolic BP Maximum Change From Baseline [ Time Frame: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes ]
4. Pulse Rate Maximum Change From Baseline [ Time Frame: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

United States, Pennsylvania

University of Pennsylvania, School of Dental Medicine

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

St. Renatus, LLC

Ground Zero Pharmaceuticals

Rho, Inc.

Investigators

• Principal Investigator: Elliot V Hersh, DMD, MS, PhD; University of Pennsylvania

More Information

• Responsible Party: St. Renatus, LLC
• ClinicalTrials.gov Identifier: NCT01304316
• Other Study ID Numbers: SR 2-02
• First Posted: February 25, 2011
• Results First Posted: August 31, 2017
• Last Update Posted: August 31, 2017
• Last Verified: July 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Additional relevant MeSH terms:

Phenylephrine; Oxymetazoline; Tetracaine; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Sympathomimetics; Autonomic Agents; Nasal Decongestants; Vasoconstrictor Agents; Respiratory System Agents; Cardiotonic Agents; Mydriatics; Adrenergic alpha-1 Receptor Agonists; Protective Agents