Study of OraVerse® for Safety and Efficacy in Pediatric Dental Patients

A Phase 4, Multicenter, Randomized, Double-Blinded, Controlled Study of OraVerse® for Safety and Efficacy in Pediatric Dental Patients Undergoing Mandibular and Maxillary Procedures

The purpose of this study is to determine whether OraVerse is safe and effective for the reversal of dental anesthesia in children 2 to 5 years of age weighing at least 10 kg.

Study Overview

• Status: Completed
• Conditions: Anesthesia, Local; Dental Anesthesia; Anesthesia, Reversal
• Intervention / Treatment: Drug: OraVerse; Other: Sham injection

Detailed Description

This Phase 4 clinical study is designed as a multicenter, randomized, double-blinded, controlled study to evaluate the safety and efficacy of OraVerse in approximately 150 children 2 to 5 years of age. OraVerse or sham injection is administered at the completion of a dental procedure requiring local anesthesia with lidocaine 2% with 1:100,000 epinephrine. The dental procedure(s) comprising restoration/fillings shall be performed in a single quadrant of the mouth.

The primary endpoint is safety and tolerability of OraVerse as measured by adverse events, vital signs, oral cavity assessments, nerve injury, and analgesics for intraoral pain. Secondary objectives in subjects 4 and 5 years of age include the safety and tolerability of OraVerse as measured by pain assessments using W-B PRS and evaluation of efficacy assessed by a pediatric Functional Assessment Battery (pFAB) and standardized lip and tongue palpation procedure.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Dentistry
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-6030
      • University of Pennsylvania School of Dental
    • Pittsburgh, Pennsylvania, United States, 15261
      • University of Pittsburgh School of Dental Medicine
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Jean Brown Research
  • Washington
    • Seattle', Washington, United States, 98115
      • Center for Pediatric Dentistry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, 2 to 5 years of age
• Sufficiently healthy as determined by the Investigator to receive routine dental care
• Requires a restorative procedure (restoration/filling) in a single quadrant of the mouth
• Requires local anesthesia with lidocaine 2% with 1:100,000 epinephrine administered by submucosal injection
• For subjects undergoing mandibular procedures, require an inferior alveolar nerve block for the restorative procedure
• Dental procedure(s) completed within 60 minutes of injection of local anesthetic
• For subjects 4 and 5 years of age, can be trained in standardized lip/tongue palpation procedure and pFAB

• Subjects who are trainable in pFAB and standardized lip/tongue palpation procedure have either:

  • normal pFAB at baseline prior to administration of local anesthetic and
  • at least one abnormal function (smiling, speaking, drinking or drooling) at the completion of the dental procedure OR
  • normal lip sensation at baseline prior to administration of local anesthetic and
  • numbness of the relevant lip quadrant at completion of the dental procedure
• Subjects give written or verbal assent, as capable and appropriate, and parent(s) or legal guardian(s) give written informed consent

Exclusion Criteria:

• Weight less than 10 kg
• Weight less than 15 kg if 4 or 5 years of age
• History or presence of any condition that contraindicates routine dental care or use of local anesthetic
• Requires more than ¼ cartridge of local anesthetic if weight is ≥ 10 kg and < 15 kg, more than ½ cartridge of local anesthetic if weight is ≥ 15 kg and < 30 kg, and more than 1 cartridge of local anesthetic if weight is ≥ 30 kg, excluding supplemental injections
• Allergy or intolerance to lidocaine, epinephrine, sulfites, phentolamine, nitrous oxide or topical benzocaine
• Has used any investigational drug and/or participated in any clinical study within 30 days of study drug administration
• Has participated in this study or any previous study of phentolamine mesylate for reversal of local soft tissue anesthesia (STA)
• Any use of commercial OraVerse™ within 30 days of study drug administration
• Use of opioid or opioid-like analgesics within 24 hours prior to administration of local anesthetic
• Requires the use of local anesthetic other than lidocaine 2% with 1:100,000 epinephrine to perform the scheduled dental procedure
• Requires the use of general anesthesia or sedatives except for nitrous oxide to perform the scheduled dental procedure
• Any condition which in the opinion of the Investigator increases the risk to the subject of participating in this study or decreases the likelihood of compliance with the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OraVerse; OraVerse in doses of either 1/4, 1/2 or 1 cartridge (1.8mL)	Drug: OraVerse; 1.8mL dental cartridge delivered in doses of either 1/4, 1/2 or 1 cartridge depending on subject weight
Sham Comparator: Sham injection; Dentist simulates injection with dental syringe	Other: Sham injection; No drug administered, simulation of injection used in same manner as drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events		Up to 3 days
Clinically significant changes in vital signs	Blood pressure and pulse	Up to 3 days
Clinically significant changes in oral cavity assessments		Up to 3 days
Nerve injury		Up to 3 days
Analgesics required for intraoral pain		Up to 3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence, severity and duration of intraoral pain as measured by W-B PRS	Wong-Baker Pain Rating Scale used to assess subject pain	Up to 3 days
Time to normal function	Measured by pediatric Functional Assessment Battery (pFAB) to determine when speaking, eating, drinking, drooling return to baseline	Up to 3 days
Time to normal lip sensation	Measures time to normal lip and tongue sensation using standardized lip/tongue palpation procedure	Up to 3 days
Time to normal tongue sensation	Measures time to normal tongue sensation using standardized lip/tongue palpation procedure	Up to 3 days

Collaborators and Investigators

• Sponsor: Novocol Pharmaceutical of Canada, Inc.
• Investigators: Principal Investigator: Paul Moore, DMD,PhD,MPH, University of Pittsburgh School of Dental Medicine; Principal Investigator: Elliot Hersh, DMD,MS,PhD, University of Pennsylvania; Principal Investigator: Joel Berg, DDS,MS, Seattle Children's Hospital; Principal Investigator: Judith Chin, DDS,MS, Indiana University; Principal Investigator: Brent Lin, DMD, University of California, San Francisco; Principal Investigator: Paul Casamassimo, MS,DDS, Nationwide Children's Hospital; Principal Investigator: Adam Marberger, DDS, Jean Brown Research

Publications and helpful links

General Publications

• Hersh EV, Moore PA, Papas AS, Goodson JM, Navalta LA, Rogy S, Rutherford B, Yagiela JA; Soft Tissue Anesthesia Recovery Group. Reversal of soft-tissue local anesthesia with phentolamine mesylate in adolescents and adults. J Am Dent Assoc. 2008 Aug;139(8):1080-93. doi: 10.14219/jada.archive.2008.0311.
• Moore PA, Hersh EV, Papas AS, Goodson JM, Yagiela JA, Rutherford B, Rogy S, Navalta L. Pharmacokinetics of lidocaine with epinephrine following local anesthesia reversal with phentolamine mesylate. Anesth Prog. 2008 Summer;55(2):40-8. doi: 10.2344/0003-3006(2008)55[40:POLWEF]2.0.CO;2.
• Tavares M, Goodson JM, Studen-Pavlovich D, Yagiela JA, Navalta LA, Rogy S, Rutherford B, Gordon S, Papas AS; Soft Tissue Anesthesia Reversal Group. Reversal of soft-tissue local anesthesia with phentolamine mesylate in pediatric patients. J Am Dent Assoc. 2008 Aug;139(8):1095-104. doi: 10.14219/jada.archive.2008.0312. Erratum In: J Am Dent Assoc. 2008 Oct;139(10):1312.
• Laviola M, McGavin SK, Freer GA, Plancich G, Woodbury SC, Marinkovich S, Morrison R, Reader A, Rutherford RB, Yagiela JA. Randomized study of phentolamine mesylate for reversal of local anesthesia. J Dent Res. 2008 Jul;87(7):635-9. doi: 10.1177/154405910808700717.

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: November 11, 2011
• First Submitted That Met QC Criteria: November 16, 2011
• First Posted (Estimate): November 18, 2011

Study Record Updates

• Last Update Posted (Estimate): August 29, 2014
• Last Update Submitted That Met QC Criteria: August 28, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Pediatric; OraVerse; Reversal of dental anesthesia
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-Antagonists; Phentolamine
• Other Study ID Numbers: PHE-11-001