Safety and Efficacy of Merlin (Ethanol and Glycolic Acid Mixture) for Episodic Treatment of Cold Sores

• Merlin (Drug): glycolic acid/ethanol solution
• Ethanol (Drug): Ethanol solution

Primary outcomes

• Clinician Assessed Duration of the Classical Herpetic Lesion [From time of beginning of treatment until onset of Lesion Stage 6 or Stage 7, if Stage 6 never observed, with a maximum of 14 days.]: The time in hours from beginning of treatment to onset of Stage 6 (residual swelling) or Stage 7 (complete healing) if Stage 6 never observed

Secondary outcomes

• Clinician Assessed Duration of the Herpetic Episode [For classical lesions: from the beginning of the treatment until loss of hard crust (Stage 6); for non-classical lesions the time from the beginning of treatment until complete resolution of all local signs and symptoms (Stage 7) - maximum of 14 days]: For classical lesions: the time in hours from the beginning of the treatment until loss of hard crust (Stage 6); for non-classical lesions the time from the beginning of treatment until complete resolution of all local signs and symptoms (Stage 7)
• Clinician Assessed Duration Until Complete Healing of the Herpetic Episode [From the beginning of treatment to onset of Stage 7 - maximum of 14 days]: The time, in hours, from the beginning of treatment to onset of Stage 7
• Clinician Assessed Prevention of Progression to Classical Lesion [14 days maximum]: Proportion of subjects in each treatment group who do not display classical lesions
• Clinician Assessed Lesion Size [14 days maximum]: Maximum lesion area for ulcerative lesions during Stages 3-5
• Clinician Assessed Duration of the Herpetic Lesion Hard Scab [From start of Stage 5 to loss of hard crust - maximum of 14 days]: Duration of the hard crust (Stage 5)
• Subject Assessed Duration of Pain [From time of first occurrence of at least mild pain to time of consistent scoring of no pain - maximum 14 days]: Time of first occurrence of at least mild pain to consistent scoring of no pain

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* Male or female subject 18-75 years of age
* Female subjects must be using a medically acceptable form of birth control during the study. Acceptable birth control measures include, but are not limited to: abstinence, oral contraceptive pills or patch, injectable contraception, barrier contraceptives (condom, diaphragm with spermicide), IUD, vaginal contraceptive ring, surgical (hysterectomy, tubal ligation), vasectomized partner, and natural post-menopausal inability to conceive. Menopause is defined for this protocol as starting one year after the time of the last menstrual period.
* Subject must have a history of recurrent herpes labialis and report at least 3 separate recurrences (i.e. multiple herpetic lesions in one outbreak count as only one episode) during the preceding 12 months.
* Subject must have a history of experiencing prodromal symptoms of cold sores (e.g. itching, tingling, or burning) during at least half of their previous cold sore episodes.
* Subject must have a history of at least half of their cold sore episodes producing classical lesions (i.e., episodes that progressed through macule, papule, vesicle, crust, and healed).
* Subject must provide voluntary written informed consent to participate in this study.
* Subject is able to appear for a clinic visit within 24 hours from the time of treating cold sore and is able to return to the clinic for the full 14 day duration of the study if necessary.

Exclusion Criteria:

* Subjects with evidence of active malignancy or immunodeficiency disease within the last 30 days. Subjects who have completed therapy and are considered unlikely to relapse or who have had surgery and do not have any evidence of disease, are eligible for the study.
* Subject requires chronic use of immunomodifying drugs (e.g. systemic steroids) or topical steroids on or near the face; use of inhaled steroids does not exclude a subject from the study. If a subject is unlikely to get through the Treatment Phase of the protocol without requiring the use of an immunomodifying drug for a chronic condition the subject should be excluded.
* Subject requires chronic use of anti-viral medication. In females of childbearing potential, a positive urine pregnancy test at time of screening.

Nursing mothers.

* Subject has abnormal skin conditions (e.g. acne, eczema, rosacea, psoriasis, albinism, or chronic vesiculobullous disorders) that occur in the area ordinarily affected by cold sores or has significant facial hair in the area of the cold sore that might affect the normal course of the cold sore or might impair accurate evaluation of the cold sore lesion.
* Subject has had a vaccine for herpes simplex virus type 1 (typically oral herpes) or 2 (typically genital herpes).
* Subject is currently enrolled in another clinical trial involving the use of a drug and/or a device.
* Subject requires chronic use of analgesics or non-steroidal anti-inflammatory agents (NSAIDs) except for low doses of aspirin (less than 325 mg/day) used for cardiovascular purposes. If a subject is unlikely to get through the Treatment Phase of the protocol without requiring the use of analgesia for a chronic condition, e.g. back pain, recurrent daily headaches, the subject should be excluded.

Participant flow

Outcome results

• Clinician Assessed Duration of the Classical Herpetic Lesion (Primary), Mean, hours: Merlin 162.7 +/- 68.4; Ethanol 163.6 +/- 74.9
• Clinician Assessed Duration of the Herpetic Episode (Secondary), Mean, hours: Merlin 151.1 +/- 70.9; Ethanol 158.6 +/- 74.5
• Clinician Assessed Duration Until Complete Healing of the Herpetic Episode (Secondary), Mean, hours: Merlin 223.4 +/- 83.2; Ethanol 222.0 +/- 86.4
• Clinician Assessed Prevention of Progression to Classical Lesion (Secondary), Count of participants, Participants: Merlin 12; Ethanol 6
• Clinician Assessed Lesion Size (Secondary), Mean, square mm: Merlin 46.8 +/- 50.2; Ethanol 36.2 +/- 43.7
• Clinician Assessed Duration of the Herpetic Lesion Hard Scab (Secondary), Mean, hours: Merlin 66.6 +/- 56.8; Ethanol 65.9 +/- 62.3
• Subject Assessed Duration of Pain (Secondary), Count of participants, Participants: Merlin 31; Ethanol 35

Adverse events

Time frame: Adverse event data was collected during the course of treatment until the herpetic lesion healed, or for 14 days from the first report of a cold sore, whichever occurred first, for all those who developed a cold sore in the study, and for two weeks after completion of treatment or for two weeks after the 14 day Treatment Phase study period.

Other adverse events by term

• Study Protocol (PDF, 2017-04-18)
• Statistical Analysis Plan (PDF, 2017-08-23)

• Stephen A Bart, Sr., M.D., Principal investigator, Optimal Research Rockville MD
• Murray A Kimmel, DO, Principal investigator, Optimal Research Melbourne FL
• Daniel H Brune, MD, Principal investigator, Optimal Research Peoria IL
• Stephen Daniels, DO, Principal investigator, Optimal Research Austin TX
• Randle T Middleton, MD, Principal investigator, Optimal Research Huntsville AL
• Patrick Yassini, MD, Principal investigator, Optimal Research San Diego CA