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Dose-Escalation Safety and Pharmacokinetic Study of K305

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01304316
First Posted: February 25, 2011
Last Update Posted: August 31, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Ground Zero Pharmaceuticals
Rho, Inc.
Information provided by (Responsible Party):
St. Renatus, LLC
  Purpose
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 Intervention Phase
Anesthesia Drug: Tetracaine HCl 3% and Oxymetazoline HCl 0.05% Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by St. Renatus, LLC:

Primary Outcome Measures:
  • 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

  • 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

  • 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

  • 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

  • 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

  • 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:
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]

Enrollment: 12
Study Start Date: September 2010
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01304316


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     History of Changes
Other Study ID Numbers: SR 2-02
First Submitted: February 18, 2011
First Posted: February 25, 2011
Results First Submitted: November 2, 2016
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:
Tetracaine
Oxymetazoline
Phenylephrine
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