Topical Application of Cocaine HCl 4%, or 10%, or Placebo Solution in Local (Topical) Anesthesia
Condition: Any Ear Nose or Throat Conditions; With Identified Need for a Diagnostic Procedure or Surgery on or Through the Mucous Membranes of the Nasal Cavities
Intervention: Cocaine HCl 4% Topical Solution; Cocaine HCl 10% Topical Solution; Placebo Topical Solution
Intervention description: Topical solution, up to 4 mL, is applied for 20 minutes via cotton or rayon pledget(s) to the accessible mucous membranes of the nasal cavities.; Topical solution, up to 4 mL, is applied for 20 minutes via cotton or rayon pledget(s) to the accessible mucous membranes of the nasal cavities.; Topical solution, up to 4 mL, is applied for 20 minutes via cotton or rayon pledget(s) to the accessible mucous membranes of the nasal cavities.
Intervention MeSH terms: Cocaine; Pharmaceutical Solutions
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 646.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Ear; Nose; Throat

Summary:

      Randomized, prospective, multi-center, double blind placebo-controlled parallel group study
      of a Placebo Topical Solution versus Cocaine HCl 4% Topical Solution for safety and efficacy,
      and Cocaine HCl 4% and 10% Topical Solution for Safety as an anesthetic prior to a diagnostic
      procedure or surgery on or through accessible mucous membranes of the nasal cavities. Both
      domestic (United States) and foreign sites are eligible, and both inpatient and outpatient
      settings are eligible.
    

Eligibility criteria:

        Inclusion Criteria:

        - Subjects must meet all of the following criteria prior to enrollment in the study:

          -  Provide written informed consent and HIPAA authorization. Residents of California must
             also review and sign the California Subject Bill of Rights.

          -  Male or female ≥18 years of age.

          -  Predetermined need from a physician for diagnostic procedure or surgery on or through
             the nasal mucous membranes of either one or two nostrils that merits the use of
             anesthesia.

          -  Ability to feel pain sensation normally in the nasal mucous membranes, as verified via
             Von Frey 5.88 monofilament testing

          -  Ability to clearly communicate pain and sensation of the nasal mucous membranes.

        Exclusion Criteria:

          -  Has a known allergy to any ester based anesthetics including cocaine, procaine,
             tetracaine, chlorprocaine, dibucaine, or benzocaine and/or any other compounds of the
             drugs and/or devices that are part of this protocol. (Amide based or other non-ester
             based anesthetic allergies are NOT exclusionary. Amide based anesthetics are:
             Lidocaine, Mepivicaine, Bupivicaine, Levobupivicaine, Ropivicaine, Etidocaine,
             Prolicaine, and Articaine).

          -  Has a history of abuse of controlled substances, nasal or otherwise, or has damage to
             the nasal space, that in the opinion of the investigator might interfere with the
             ability of the subject or the investigator to judge anesthesia from the trial drug.

          -  Has used any investigational drug(s) within 30 days preceding the randomization.

          -  Is pregnant or is a nursing mother

          -  Women of childbearing potential (WOCBP) and male partners of WOCBP who are not willing
             to use an acceptable method of contraception to avoid pregnancy throughout the study.
             Contraceptive practices must extend for women at least 30 days and for male partners
             of WOCBP at least 90 days after the last dose of investigational product in such a
             manner that the risk of pregnancy or risk to a pregnancy is minimized.

          -  Is < 18 years of age

          -  Suffers from a condition, other than the need for a diagnostic procedure or surgery on
             or through the nasal mucous membranes which, in the opinion of the Investigator, would
             compromise the safety of the subject, the quality of the data, or the normal wound
             healing process.

          -  Use of any analgesic 2 days prior to screening or has a need to use these drugs during
             the screening period. This includes NSAIDs, such as ibuprofen, diclofenac,
             indomethacin, sulindac, tolmetin, ketoprofen, flurbiprofen, naproxen, opioids such as
             codeine, hydrocodone, hydromorphone, morphine, oxycodone, aspirin, or acetaminophen.

          -  Subjects who have experienced a seizure while taking isoniazid (INH), phenothiazines,
             chlorpromazine, thioridazine, theophylline, or tricyclic antidepressants such as
             amitriptyline.

          -  Has previously received study drug during this study. Subjects who fail screening may
             rescreen if eligibility requirements are met, but only if the subject has not received
             any study drug during this study.

          -  Has a history of myocardial infarction, coronary artery disease, congestive heart
             failure, irregular heart rhythm (as fully defined in sections 7.9.4, 7.9.5 and 7.9.6)
             or uncontrolled hypertension or is taking monoamine oxidase inhibitors (6).
             Uncontrolled hypertension is defined as systolic blood pressure greater than or equal
             to 140 mm Hg or diastolic blood pressure greater than or equal to 90 mm Hg (43)(44).

          -  Has a known personal or family history of hereditary pseudocholinesterase deficiency.
             (2) Study participants will be screened by asking about personal or family history of
             anesthetic reaction, anesthetic death, and previous diagnosis of pseudocholinesterase
             deficiency in a relative or personally. Subjects identified with pseudocholinesterase
             deficiency are at risk for delayed recovery with certain anesthetics (e.g.
             succinylcholine and ester-based anesthetics). (14)

          -  Has a known personal or family history of pheochromocytoma. (2) Study participants
             will be specifically asked if they have been treated for a pheochromocytoma previously
             or if they have a family member who has been diagnosed with pheochromocytoma (since
             10% of these are familial). (14)

          -  Has a known personal or family history of an adrenal tumor.

          -  Use of amphetamines in the 2 days prior to screening or has a need to use these drugs
             during the course of the study. All stimulant prescription, and nonprescription
             products such as catecholamines (norepinephrine or epinephrine), ephedrine,
             pseudoephedrine and any other amphetamines in the 48 hours prior to screening or has a
             need to use these drugs during the course of the study. All herbal products except
             coffee, tea, or herbal tea are also prohibited within 48 hours prior to screening or
             if the subject has a need to use these drugs during the course of the study. Coffee,
             Tea, and Herbal Tea are not exclusionary criteria or prohibited medications as they
             are food products not prescription or nonprescription products.

          -  Has screening 12-lead ECG findings of any abnormalities as listed in section 7.9.4,
             7.9.5, and 7.9.6. Generally, these are current or prior myocardial ischemia or
             infarction, dysrhythmia, or risk of serious dysrhythmia (such as prolonged QT
             interval) and include any other clinically significant abnormal ECG finding that, in
             the opinion of the Investigator in consultation with the Medical Monitor, may
             potentially result in this trial being unsafe for the subject.

          -  An exception to this would be 7.9.5.11 (resting sinus bradycardia or resting sinus
             tachycardia to a limit of 110 beats per minute) as these represent normal variants
             that may be found in younger or older healthy adults. (36)

          -  Hemoglobin <8.5 g/dL; a one-time retest will be allowed for Hb 8.3- 8.4 g/dL

          -  WBC < 3.5 x 103 cells/mcL; a one-time retest will be allowed for WBC 3.3-3.4 x 103
             cells/mcL

          -  Platelets < 100 x 103 platelets/mcL; a one-time retest will be allowed for platelets
             90-99x 103 platelets/mcL

          -  Serum Potassium <3.5 or >5.0 mEq/L

          -  Serum ALT, AST, and bilirubin exceeding 2X ULN for the lab's reference values

          -  Cardiac enzymes above the range of normal

          -  Coagulation studies that in the opinion of the investigator would be cause for the
             subject to be excluded from the study.

          -  Positive urine pregnancy test at screening or Day 1

          -  Positive urine drug test at screening or Day 1 without prior medically-necessary use
             of controlled substances (for example, benzodiazepines for anxiety)

          -  Subjects is a member of the Investigational Team, including Investigators or
             Sub-Investigators, or their immediate family.

        A one-time retest is permitted for any blood test if the original sample was hemolyzed.