Clinical trial NCT03233737: Pain Study to Assess Local Anesthetic Efficacy and Safety of CTY-5339 on Gingival Mucosal Tissue in Normal Volunteers
Official title: A Double-blind, Cross-over, Incomplete Factorial Study to Assess the Local Anesthetic Efficacy and Safety of CTY-5339 Anesthetic Spray (CTY-5339A) When Applied to the Gingival Mucosal Tissue in Normal Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: No Disease State or Condition
Keywords: local anesthesia
pain tolerance
experimental pain
Lead sponsor: Cetylite Industries
Sponsor class: INDUSTRY
First posted: 2017-07-31
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine if the topical application to gingival tissue of the combination of benzocaine and tetracaine has a longer duration of local anesthetic activity than benzocaine alone.

Detailed description: In a blinded study, either benzocaine alone or the combination of benzocaine and tetracaine will be sprayed onto the gingival mucosal tissue. Onset and duration of local anesthesia will be evaluated over a one hour period using pin prick and quantitative sensory testing of heat (QST-heat) stimulation. Subjects will receive both treatments in a cross-over design with each session separated by 4-14 days. A total of 50 subjects (normal volunteers) will be evaluated.

Eligibility criteria: Inclusion Criteria:

* Male and female subjects between 18-75 years of age with a Body Mass Index (BMI) ≤32;
* Subjects are category I or II on the American Society of Anesthesiologists physical status classification system (ASA category I or II) and are in normal physical health as judged by physical and laboratory examinations;
* Subjects have normal appearance of the oral mucosal tissues;
* At screening and at Baseline during Stage 1 and Sessions 1 and 2, of Stage 2 subjects with Pin-Prick-Test (PPT) scores of at least "3" (on a 10 point numerical rating scale \[NRS\]) on the 2 readings, 1 of which must be a score of at least "4";
* Subjects have mean quantitative sensory test of heat (QST-Heat) pain sensation temperature assessments on the gingival mucosa of 46.5 °C or less based on the average of the 2 readings at screening and at the Baseline Study Sessions for Stages 1 and 2;
* Subjects must agree to refrain from ingesting any systemic or topical analgesic medication for 3 days or 5 half-lives of the drug prior to and during the study period and alcohol for 1 day prior to and during the study period;
* Subjects must agree to refrain from using mouth rinses, cough drops or throat lozenges on the day of each test session;
* Female subjects must be physically incapable of childbearing potential (postmenopausal for more than 1 year or surgically sterile) or practicing an acceptable method of contraception (hormonal, barrier with spermicide, intrauterine device, vasectomized or same sex partner, or abstinence). Subjects using hormonal birth control must have been on a stable dose of treatment for at least 30 days and received at least 1 cycle of treatment prior to randomization. At Screening and at Baseline of both sessions, all females of childbearing potential must have a negative urine pregnancy test and not be breastfeeding;
* Negative urine drug screen for drugs of abuse at Screening and at Baseline for each Study Session. A positive drug screen result may be permitted if the subject has been on a stable dose of an allowed medication for \>30 days;
* Subjects must be capable of reading, comprehending, and signing the informed consent form.

Exclusion Criteria:

* Subjects with a history of any significant hepatic, renal, endocrine, cardiac, neurological, psychiatric, gastrointestinal, pulmonary, hematologic, or metabolic disorders, including glaucoma, diabetes, emphysema, and chronic bronchitis;
* Subjects with a history of any type of cancer other than skin related cancers;
* Subjects with conditions that affect the absorption, metabolism, or passage of drugs out of the body, (e.g., sprue, celiac disease, Crohn's disease, colitis, or liver, kidney, or thyroid conditions);
* Subjects with any history of alcohol or substance abuse (including a positive drug screen test);
* Subjects that currently have or have a history of uncontrolled hypertension;
* Subjects with a known hypersensitivity to any local anesthetic drug;
* Subjects with a hematocrit level significantly below the normal range on the screening laboratory examination (as judged by the PI);
* Subjects with any clinically significant abnormal lab result (as judged by the PI);
* Subjects with any condition or history felt by the Investigator to place the subject at increased risk;
* Subjects who have smoked or chewed tobacco-containing substances within 6 months prior to the start of the study;
* Subjects judged by the Investigator to be unable or unwilling to comply with the requirements of the protocol;
* Subjects who have used an investigational drug within 30 days prior to entering the study;
* Subjects who have donated blood within 3 months prior to the start of the study;
* Subjects who have previously participated in the trial;
* Subjects who are members of the study site staff directly involved with the study or a relative of the Sponsor or other personnel involved with the study.

Primary outcomes:
measure: Stage II: Duration of Anesthesia as Measured by Pin Prick Test (PPT) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB
timeFrame: Up to one hour post-application
measure: Stage II: Duration of Anesthesia as Measured by Heat Sensation Threshold (QST Heat) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB
timeFrame: Up to one hour post-application
measure: Stage I: Duration of Anesthesia as Measured by Pin Prick Test (PPT) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB Compared to One Spray CTY-5339-P (Placebo: Vehicle Control)
timeFrame: Up to one hour post-application
measure: Stage I: Duration of Anesthesia as Measured by Heat Sensation Threshold (QST Heat) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB Compared to One Spray CTY-5339-P (Placebo: Vehicle Control)
timeFrame: Up to one hour post-application
Secondary outcomes:
measure: Stage II: Onset of Anesthesia for Pin Prick Test (PPT)
timeFrame: Up to one hour post-application
measure: Stage II: Onset of Anesthesia for Heat Sensation Threshold (QST Heat)
timeFrame: Up to one hour post-application
measure: Stage II: Percentage of Responders for Pin Prick Test (PPT) at Each Time Point
timeFrame: Up to one hour post-application
measure: Stage II: Percentage of Responders for Heat Sensation Threshold (QST Heat) at Each Time Point
timeFrame: Up to one hour post-application
measure: Stage II: Percentage of Subjects Reaching Minimal Pain on Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)
timeFrame: Any time within one hour post-application
measure: Stage II: Duration of Minimal Pain for Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)
timeFrame: Up to one hour post-application
measure: Stage II: Percentage of Subjects Reaching Maximum Heat for Heat Sensation Threshold (QST Heat)
timeFrame: Any time within one hour post-application
measure: Stage II: Sum of Pain Intensity Differences (SPID) for Pin Prick Test (PPT) (Post-hoc)
timeFrame: Up to one hour post-application
measure: Stage II: Sum of Temperature Differences (STID) for Heat Sensation Threshold (QST Heat) (Post-hoc)
timeFrame: Up to one hour post-application
measure: Stage I: Percentage of Responders for Pin Prick Test (PPT) at Each Time Point
timeFrame: Time of application up to one hour post-application
measure: Stage I: Percentage of Responders for Heat Sensation Threshold (QST Heat) at Each Time Point
timeFrame: Time of application up to one hour post-application
measure: Stage I: Duration of Minimal Pain for Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)
timeFrame: Up to one hour post-application
measure: Stage I: Percentage of Subjects Reaching Maximum Heat for Heat Sensation Threshold (QST Heat)
timeFrame: Any time within one hour post-application
measure: Stage I: Onset of Anesthesia for Pin Prick Test (PPT)
timeFrame: Up to one hour post-application
measure: Stage I: Onset of Anesthesia for Heat Sensation Threshold (QST Heat)
timeFrame: Up to one hour post-application
measure: Stage I: Percentage of Subjects Reaching Minimal Pain on Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)
timeFrame: Any time within one hour post-application
measure: Stage I: Sum of Pain Intensity Differences (SPID) for Pin Prick Test (PPT) (Post-hoc)
timeFrame: Up to one hour post-application
measure: Stage I: Sum of Temperature Differences (STID) for Heat Sensation Threshold (QST Heat) (Post-hoc)
timeFrame: Up to one hour post-application
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania, School of Dental Medicine
state: Pennsylvania
Study officials:
name: Stephen A Cooper, DMD, PhD
role: STUDY_CHAIR
References:
citation: Hersh EV, Secreto S, Wang S, Giannakopoulos H, Mousavian M, Lesavoy B, Hutcheson MC, Farrar JT, Wang P, Doyle G, Cooper SA. A Proof-of-concept Study Using Quantitative Sensory Threshold Analysis to Compare Two Intraoral Topical Anesthetics. Clin Ther. 2019 Feb;41(2):291-302. doi: 10.1016/j.clinthera.2018.12.009. Epub 2019 Jan 17.