Topical Application of Cocaine HCl 4% and 10% on Safety and Efficacy in Local (Topical) Anesthesia

A Phase III Investigation of Topical Application of Cocaine HCl 4% and 10% on Safety and Efficacy in Local (Topical) Anesthesia for Diagnostic Procedures and Surgeries on or Through Accessible Mucous Membranes of the Nasal Cavities.

This study aims to evaluate topical application of Cocaine HCl 4% and 10% on safety and efficacy in local (topical) anesthesia for diagnostic procedures and surgeries on or through accessible mucous membranes of the nasal cavities.

Randomized, prospective, multisite, double-blind, placebo-controlled, parallel-group study of a Placebo Topical Solution versus Cocaine HCl 4% or 10% Topical Solution as an anesthetic prior to a diagnostic procedure or surgery.

In the Safety and Efficacy first phase, subjects will be randomized in a 1:1:1 fashion to one of the three treatment groups (placebo, Cocaine HCl 4% or 10% topical solution) pre-procedure and given one application of up to 4 mL from one bottle of the assigned test product. After pre-procedure Von Frey filament testing, the blind will be broken, but only relative to placebo versus cocaine, not relative to the strength of the cocaine. The placebo subjects will then exit participation in the efficacy portion of the trial, and be followed for safety for 7 days. Treatment group subjects who do not feel pain after Von Frey testing will receive their surgery or diagnostic procedure and also be followed for safety for 7 days.

In the Safety second phase, subjects will be randomized in a 1:1 fashion to one of the two treatment groups (Cocaine HCl 4% or 10% topical solution) pre-procedure and given one application of up to one 4 mL of the assigned test product. After pre-procedure Von Frey filament testing reveals a pain score of 0, subjects will receive their surgery or diagnostic procedure, and then all subjects will be followed for safety for 7 days.

Inclusion Criteria:

• 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 a diagnostic procedure or surgery of or through the nasal mucous membranes of either one or two nostrils.
• Ability to feel pain sensation normally in the nasal mucous membranes, as verified via Von Frey 5.18 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 HCl, procaine, tetracaine, chloroprocaine, dibucaine, or benzocaine, and/or any other compounds of the drugs and/or devices that are part of this protocol. (Amide based anesthetic allergies are NOT exclusionary. Amide based anesthetics are: Lidocaine, Mepivicaine, Bupivicaine, Levobupivicaine, Ropivicaine, Etidocaine, Prilocaine, 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 men must be using an acceptable method of contraception to avoid pregnancy throughout the study, and for women 30 days and men 90 days after the last dose of investigational product in such a manner that the risk of pregnancy and risk to pregnancy is minimized.
• Is < 18 years of age
• Suffers from a condition, other than the need for a diagnostic procedure or surgery of or through the nasal mucous membranes which, in the opinion of the Investigator, would compromise the safety of the subject and/or 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 NSAID 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.
• Has a history of myocardial infarction, coronary artery disease, congestive heart failure, irregular heart rhythm (as fully defined in sections 9.4, 9.5, and 9.6 of the protocol), or uncontrolled hypertension or is taking (or has recently taken) monoamine oxidase inhibitors. 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
• Has a known personal or family history of hereditary pseudocholinesterase deficiency. 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).
• Has a known personal or family history of pheochromocytoma. 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).
• 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 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.
• Has screening 12-lead ECG findings of any abnormalities as listed in sections 7.9.4, 7.9.5, and 7.9.6 of the protocol. Generally, these are current or prior myocardial ischemia or infarction, dysrhythmia, or risk of serious dysrhythmia (such as prolonged QT interval) An exception to this would be from 7.9.5.11 if sinus bradycardia or sinus tachycardia is present, the Investigator must determine whether this finding is clinically relevant and exclusionary.
• 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 >4.5 mEq/L
• Serum ALT, AST, and bilirubin not exceeding 2X ULN for the lab's reference values
• Cardiac enzymes outside of 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)
• A one-time retest is permitted for any blood test if the original sample was hemolyzed.