Pediatric Study to Access Pharmacokinetics and Safety of Oraqix Gel

Study Overview
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Brief Summary
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To establish Oraqix is safe when used on adolescent volunteers.

Detailed Description
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This is a single-center, uncontrolled, open-label, single administration patient study. Male and female subjects aged 6 through 17 years of age in need of primary tooth extraction will be recruited from the Principal Investigator's database and may be supplemented by advertising. Subjects who withdraw from the study prematurely will be replaced. Subjects will undergo an initial screening visit at which eligibility will be determined. After completion of informed consent/assent a physical examination, vitals, 12-lead ECG, and dental examination will be conducted. A medical history will be documented and a blood sample will be collected for analysis of biochemistry, hematology and as appropriate, serum pregnancy assessment for females. Subjects will return to the office approximately 1 to 10 days after Visit 1 for Visit 2. At Visit 2, study treatment will be administered and PK blood samples will be collected for analysis, and monitored for safety parameters. Up to a total of five cartridges of Oraqix® will be administered to the oral cavity in the area of the tooth extraction, based on the body weight of the subject. No more than five cartridges will be dispensed, since this is the maximum dose for this agent. The final sample will be collected 4 hours after administration of study material. An abbreviated dental examination will be conducted, any adverse events (AEs) will be documented and the subject will be discharged from the clinic. All subjects will be contacted by telephone approximately 24 hours after administration of study treatment. Study personnel will enquire about the occurrence of any AEs that have occurred since leaving the office. If appropriate, further follow-up of AEs will be arranged. In the absence of any ongoing AEs requiring follow up the subject will be considered to have completed the study at the completion of the telephone call.

Official Title
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A Phase 4 Pediatric Study to Assess the Pharmacokinetics and Safety of Oraqix Gel in Healthy Children and Adolescent Volunteers Following Tooth Extraction

Conditions
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Periodontal Disease

Intervention / Treatment
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* Drug: lidocaine and prilocaine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 6 and 17 and eleven twelfths requires tooth extraction healthy having not taken any prescription or over the counter medications within 60 days of first visit must be a minimum of 15 kg Exclusion Criteria: anesthesia required for treatment other than study material given blood within 90 days of first visit pregnant allergic to local anesthetic documented history of glucose-6-phosphate dehydrogenase deficiency history of congenital idiopathic methemoglobinemia does not have a loose tooth easily extracted or who, in the opinion of the Investigator, is not suitable for tooth extraction using only topical anesthetic

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Oraqix for tooth extraction<br> | Drug: lidocaine and prilocaine<br>* Appropriate dose of Oraqix based on weight will be given before tooth extraction<br>* Other names: Oraqix periodontal gel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics | The study focused on the pharmacokinetics of prilocaine and lidocaine, o-toluidine (metabolite of prilocaine) and 2, 6-xylidine (metabolite of lidocaine). We evaluated blood samples of15 subjects at the following time points: pre-dose, at 5,10,15,30, 60, 90, 120 and 240 min post dose. We calculated Cmax (maximum observed plasma concentration) and Tmax (time to maximum plasma concentration). | 5, 10, 15, 30, 60, 90, 120, and 240 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | The % MetHb levels and vital signs (pulse, systolic and diastolic pressure) were measured at pre-dose (-20, -10 and 0 min prior to Oraqix administration) and every 10 minutes up to 240 minutes post dose. ECG taken at pre-dose and 1, 2 and 4h post dose, measurement of heart rate and PR, QRS, QT and QTcB intervals. Visual analogue scale conducted at pre-dose (immediately before Oraqix administration), immed. post extraction, at 0.25, 0.5, 1 and 2h post dose and prior to discharge just after 4h post dose. For each subject, phone call was made at +24h as follow up pursuant to the protocol. | blood draws pre-dose, 2 and 4 hours postdose | 
| Vital Signs (Pulse) | Vital signs (pulse, systolic and diastolic pressure) were measured at pre-dose (-20, -10 and 0 min prior to Oraqix administration) and every 10 minutes up to 240 minutes post dose. | Pre-dose and every 10 minute to 240 minutes post-dose. | 
| Vital Signs (Systolic Pressure) |  | Pre-dose (-20, -10 and 0 min prior to Oraqix administration) and every 10 minutes up to 240 minutes post dose. | 
| Vital Signs (Diastolic Pressure) |  | Pre-dose (-20, -10 and 0 min prior to Oraqix administration) and every 10 minutes up to 240 minutes post dose | 
| ECGs (Ventricular Heart Rate) | Ventricular heart rate, PR interval, QRS duration, QT interval, and QTcB intervals were calculated. | Pre-dose, 1 hour, 2 hour, 4 hour post-dose. | 
| ECGs (PR Interval) | Ventricular heart rate, PR interval, QRS duration, QT interval, and QTcB intervals were calculated. | Pre-dose, 1 hour, 2 hour, 4 hour post-dose. | 
| ECGs (QRS Duration) | Ventricular heart rate, PR interval, QRS duration, QT interval, and QTcB intervals were calculated. | Pre-dose, 1 hour, 2 hour, 4 hour post-dose. | 
| ECGs (QT Interval) | Ventricular heart rate, PR interval, QRS duration, QT interval, and QTcB intervals were calculated. | Pre-dose, 1 hour, 2 hour, 4 hour post-dose. | 
| ECGs (QTcB Interval) | Ventricular heart rate, PR interval, QRS duration, QT interval, and QTcB intervals were calculated. | Pre-dose, 1 hour, 2 hour, 4 hour post-dose. |