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

Anesthesia, Local Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01474382
• Other study ID #: PHE-11-001
• Status: Completed
• Phase: Phase 4
• First received: November 11, 2011
• Last updated: August 28, 2014
• Start date: February 2012
• Est. completion date: August 2014

Study information

• Verified date: August 2014
• Source: Novocol Pharmaceutical of Canada, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 2 Years to 5 Years

Eligibility

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

Related Conditions & MeSH terms

• Anesthesia, Local
• Anesthesia, Reversal
• Dental Anesthesia

Intervention

Drug:
• OraVerse
1.8mL dental cartridge delivered in doses of either 1/4, 1/2 or 1 cartridge depending on subject weight

Other:
• Sham injection
No drug administered, simulation of injection used in same manner as drug

Locations

Country	Name	City	State
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Indiana University School of Dentistry	Indianapolis	Indiana
United States	University of Pennsylvania School of Dental	Philadelphia	Pennsylvania
United States	University of Pittsburgh School of Dental Medicine	Pittsburgh	Pennsylvania
United States	Jean Brown Research	Salt Lake City	Utah
United States	University of California, San Francisco	San Francisco	California
United States	Center for Pediatric Dentistry	Seattle`	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Novocol Pharmaceutical of Canada, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum in: J Am Dent Assoc. 2008 Oct;139(10):1312. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of adverse events		Up to 3 days
Primary	Clinically significant changes in vital signs	Blood pressure and pulse	Up to 3 days
Primary	Clinically significant changes in oral cavity assessments		Up to 3 days
Primary	Nerve injury		Up to 3 days
Primary	Analgesics required for intraoral pain		Up to 3 days
Secondary	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
Secondary	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
Secondary	Time to normal lip sensation	Measures time to normal lip and tongue sensation using standardized lip/tongue palpation procedure	Up to 3 days
Secondary	Time to normal tongue sensation	Measures time to normal tongue sensation using standardized lip/tongue palpation procedure	Up to 3 days