Experimental Pain Study to Assess Local Anesthetic Efficacy and Safety of CTY-5339 Anesthetic Spray in Normal Volunteers

NCT02908620 | Completed Phase 2 Results

• 1 other identifier: C-002
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Anesthesia

Outcome Measures

Primary Outcomes (2)

• Duration of Anesthesia as Measured by Pin Prick Test (PPT) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB

  Evaluations were completed at 1-minute intervals for the first 5 minutes to capture onset of anesthesia. Starting at 5 minutes after drug administration, the PPT was done at 5 minute intervals up to the one hour time point. If there was no indication of anesthesia by 10 minutes, the subject was considered a treatment failure and the assessment of PPT was discontinued. In addition, once onset of anesthesia had occurred, if there was no longer any anesthesia at two consecutive evaluation time points from 10 minutes onward, the assessment of PPT was discontinued. The PPT was assessed using a 90-mm, 26-gauge pencil-point spinal needle. At screening, 3 pin pricks were performed on each cheek. Pin pricks were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale (NRS). In order to be eligible for the study, for each cheek, subjects must have had a minimum score of "3" for the last 2 pin pricks, and one of those scores had to be "4" or higher.

  Change in pain assessment from baseline (time of application) up to one hour post-application

• Duration of Anesthesia as Measured by Heat Sensation Threshold (QST Heat) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB

  Starting at 5 minutes after drug administration, the QST was done at 5 minute intervals up to the one hour time point. If there was no indication of anesthesia by 10 minutes, the subject was considered a treatment failure and the assessment of PPT was discontinued. In addition, once onset of anesthesia had occurred, if there was no longer any anesthesia at two consecutive evaluation time points from 10 minutes onward, the assessment of QST was discontinued. The heat stimuli were delivered in 3 repetitions, with inter-stimulus intervals of 30s. The basal thermode temperature was set at a comfortable 35ºC. The rate at which the thermode heated up was set at 0.5ºC/s, while the rate at which it cooled down was set at 8ºC/s. The maximum thermode temperature was set at 51ºC. Heat sensation threshold was defined as the temperature at which the subjects first felt tingling, warmth, heat, or pain.

  Change in temperature from baseline (time of application) up to one hour post-application

Secondary Outcomes (8)

• Duration of Anesthesia as Measured by Pin Prick Test (PPT) for Two Sprays CTY-5339-A Compared to One Spray CTY-5339-CB in Combination With One Spray CTY-5339-P (Placebo)

  Time of application up to one hour post-application

• Duration of Anesthesia as Measured by QST Heat for Two Sprays CTY-5339-A Compared to One Spray CTY-5339-CB in Combination With One Spray CTY-5339-P (Placebo)

  Time of application up to one hour post-application

• Duration of Anesthesia as Measured by PPT for One Spray CTY-5339-A Compared to Two Sprays CTY-5339-A

  Time of application up to one hour post-application

• Duration of Anesthesia as Measured by QST Heat for One Spray CTY-5339-A Compared to Two Sprays CTY-5339-A

  Time of application up to one hour post-application

• Onset of Anesthesia for PPT

  Time of application up to one hour post-application

Study Arms (4)

One spray CTY-5339-A, then one spray CTY-5339-CB

EXPERIMENTAL

A single spray of CTY-5339-A Anesthetic Spray (14.0% benzocaine and 2.0% tetracaine HCl) tested over a 60 minute session, followed by a 4-14 day washout period, followed by a single spray of CTY-5339-CB Anesthetic Spray (14.0% benzocaine) tested over a 60 minute session.

Combination Product: One spray CTY-5339-A; Drug: One spray CTY-5339-CB

2 sprays CTY-5339-A, then 1 spray CTY-5339-CB +1 spray placebo

EXPERIMENTAL

Two sprays of CTY-5339-A Anesthetic Spray (14.0% benzocaine and 2.0% tetracaine HCl) tested over a 60 minute session, followed by a 4-14 day washout period, followed by a single spray of CTY-5339-CB Anesthetic Spray (14.0% benzocaine) and a single spray of vehicle control (CTY-5339-P) (sprayed outside the circumscribed area to avoid dilution of active drug) tested over a 60 minute session.

Combination Product: Two sprays CTY-5339-A; Drug: One spray CTY-5339-CB in combination with one spray CTY-5339-P (vehicle control: placebo)

One spray of CTY-5339-CB, then one spray CTY-5339-A

EXPERIMENTAL

A single spray of CTY-5339-CB Anesthetic Spray (14.0% benzocaine) tested over a 60 minute session, followed by a 4-14 day washout period, followed by a single spray of CTY-5339-A Anesthetic Spray (14.0% benzocaine and 2.0% tetracaine HCl) tested over a 60 minute session.

Combination Product: One spray CTY-5339-A; Drug: One spray CTY-5339-CB

1 spray CTY-5339-CB +1 spray placebo, then 2 sprays CTY-5339-A

EXPERIMENTAL

A single spray of CTY-5339-CB Anesthetic Spray (14.0% benzocaine) and a single spray of vehicle control (CTY-5339-P) (sprayed outside the circumscribed area to avoid dilution of active drug) tested over a 60 minute session, followed by a 4-14 day washout period, followed by a two sprays of CTY-5339-A Anesthetic Spray (14.0% benzocaine and 2.0% tetracaine HCl) tested over a 60 minute session.

Combination Product: Two sprays CTY-5339-A; Drug: One spray CTY-5339-CB in combination with one spray CTY-5339-P (vehicle control: placebo)

Interventions

One spray CTY-5339-A COMBINATION_PRODUCT

Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray.

Also known as: CTY-5339-A, CTY-5339 Anesthetic Spray, benzocaine, tetracaine, tetracaine HCl, 14.0% benzocaine, 2.0% tetracaine HCl, 2.0% tetracaine, 14.0% benzocaine and 2.0% tetracaine HCl, 14.0% benzocaine and 2.0% tetracaine, benzocaine and tetracaine HCl, benzocaine and tetracaine

One spray CTY-5339-A, then one spray CTY-5339-CB; One spray of CTY-5339-CB, then one spray CTY-5339-A

One spray CTY-5339-CB DRUG

Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray.

Also known as: CTY-5339-CB, benzocaine, 14.0% benzocaine

One spray CTY-5339-A, then one spray CTY-5339-CB; One spray of CTY-5339-CB, then one spray CTY-5339-A

Two sprays CTY-5339-A COMBINATION_PRODUCT

Metered spray bottle with ≈400 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 56 mg total) and 2.0% Tetracaine Hydrochloride (USP = 8 mg total). Administered in two anesthetic sprays.

Also known as: CTY-5339-A, CTY-5339 Anesthetic Spray, benzocaine, tetracaine, tetracaine HCl, 14.0% benzocaine, 2.0% tetracaine HCl, 2.0% tetracaine, 14.0% benzocaine and 2.0% tetracaine HCl, 14.0% benzocaine and 2.0% tetracaine, benzocaine and tetracaine HCl, benzocaine and tetracaine

1 spray CTY-5339-CB +1 spray placebo, then 2 sprays CTY-5339-A; 2 sprays CTY-5339-A, then 1 spray CTY-5339-CB +1 spray placebo

One spray CTY-5339-CB in combination with one spray CTY-5339-P (vehicle control: placebo) DRUG

A single spray of CTY-5339-CB in a metered spray bottle with ≈200 uL total spray volume, containing the active ingredient: 14.0% Benzocaine (USP = 28 mg). This was administered in combination with a single spray of CTY-5339-P (acting as vehicle control placebo with no active ingredient) in a metered spray bottle with ≈200 uL total spray volume. This combination was used to maintain double-blind conditions. The vehicle control was sprayed outside the circumscribed area to avoid dilution of active drug.

Also known as: CTY-5339-CB and Placebo, CTY-5339-CB and Vehicle Control, CTY-5339-CB and Control, benzocaine, benzocaine and Placebo, benzocaine and Vehicle Control, benzocaine and Control, 14.0% benzocaine, 14.0% benzocaine and Placebo, 14.0% benzocaine and Vehicle Control, 14.0% benzocaine and Control

1 spray CTY-5339-CB +1 spray placebo, then 2 sprays CTY-5339-A; 2 sprays CTY-5339-A, then 1 spray CTY-5339-CB +1 spray placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects between 18-75 years of age with a Body Mass Index (BMI) ≤32;
• Subjects are ASA Category I or II and are in normal physical health as judged by physical and laboratory examinations;
• Subjects with normal appearance of the oral mucosal tissues;
• 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;
• The subject is capable of reading, comprehending, and signing the informed consent form.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cetylite Industries: lead

Study Sites (1)

University of Pennsylvania, School of Dental Medicine Department of Oral & Maxillofacial Surgery

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Wang S, Giannakopoulos H, Lowstetter J, Kaye L, Lee C, Secreto S, Ho V, Hutcheson MC, Farrar JT, Wang P, Doyle G, Cooper SA, Hersh EV. Lack of Methemoglobin Elevations After Topical Applications of Benzocaine Alone or Benzocaine Plus Tetracaine to the Oral Mucosa. Clin Ther. 2017 Oct;39(10):2103-2108. doi: 10.1016/j.clinthera.2017.08.017. Epub 2017 Sep 22.

  PMID: 28943117 DERIVED

MeSH Terms

Interventions

Benzocaine; Tetracaine

Intervention Hierarchy (Ancestors)

para-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Elliot V Hersh, DMD, Ph.D., Director Clinical Pharmacology Research
• Organization: University of Pennsylvania, School of Dental Medicine

evhersh@pobox.upenn.edu

215-898-9686

Study Officials

• Elliot V Hersh, DMD, Ph.D.

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2016
• First Posted: September 21, 2016
• Study Start: December 7, 2016
• Primary Completion: April 2, 2017
• Study Completion: June 7, 2017
• Last Updated: July 2, 2019
• Results First Posted: July 2, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)