Pediatric Study to Access Pharmacokinetics and Safety of Oraqix Gel

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01591616

Enrollment

Registered

2012-05-04

Start date

2010-04-30

Completion date

2012-04-30

Last updated

2020-08-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Periodontal Disease

Brief summary

To establish Oraqix is safe when used on adolescent volunteers.

Detailed description

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.

Interventions

DRUGlidocaine and prilocaine

Appropriate dose of Oraqix based on weight will be given before tooth extraction

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

6 Years to 17 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Pharmacokinetics	5, 10, 15, 30, 60, 90, 120, and 240 minutes	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).

Secondary

Measure	Time frame	Description
Vital Signs (Pulse)	Pre-dose and every 10 minute to 240 minutes post-dose.	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.
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)	Pre-dose, 1 hour, 2 hour, 4 hour post-dose.	Ventricular heart rate, PR interval, QRS duration, QT interval, and QTcB intervals were calculated.
Safety	blood draws pre-dose, 2 and 4 hours postdose	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.
ECGs (QRS Duration)	Pre-dose, 1 hour, 2 hour, 4 hour post-dose.	Ventricular heart rate, PR interval, QRS duration, QT interval, and QTcB intervals were calculated.
ECGs (QT Interval)	Pre-dose, 1 hour, 2 hour, 4 hour post-dose.	Ventricular heart rate, PR interval, QRS duration, QT interval, and QTcB intervals were calculated.
ECGs (QTcB Interval)	Pre-dose, 1 hour, 2 hour, 4 hour post-dose.	Ventricular heart rate, PR interval, QRS duration, QT interval, and QTcB intervals were calculated.
ECGs (PR Interval)	Pre-dose, 1 hour, 2 hour, 4 hour post-dose.	Ventricular heart rate, PR interval, QRS duration, QT interval, and QTcB intervals were calculated.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Oraqix for Tooth Extraction lidocaine and prilocaine: Appropriate dose of Oraqix based on weight will be given before tooth extraction	16
Total	16

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	Oraqix for Tooth Extraction
Age, Categorical <=18 years	16 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	0 Participants
Region of Enrollment United States	16 participants
Sex: Female, Male Female	9 Participants
Sex: Female, Male Male	7 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	2 / 16
serious Total, serious adverse events	0 / 16

Outcome results

Primary

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).

Time frame: 5, 10, 15, 30, 60, 90, 120, and 240 minutes

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Lidocaine Cmax	Pharmacokinetics	89.9 ng/mL	Geometric Coefficient of Variation 66
Prilocaine Cmax	Pharmacokinetics	41.8 ng/mL	Geometric Coefficient of Variation 60.6
2,6-xylidine Cmax	Pharmacokinetics	3.72 ng/mL	Geometric Coefficient of Variation 48.5
O-toluidine Cmax	Pharmacokinetics	5.13 ng/mL	Geometric Coefficient of Variation 51.2

Primary

Pharmacokinetics

Time frame: 5, 10, 15, 30, 60, 90, 120, and 240 minutes

Arm	Measure	Value (GEOMETRIC_MEAN)
Lidocaine Cmax	Pharmacokinetics	0.500 hours
Prilocaine Cmax	Pharmacokinetics	0.500 hours
2,6-xylidine Cmax	Pharmacokinetics	1.50 hours
O-toluidine Cmax	Pharmacokinetics	1.50 hours

Secondary