Phase 3 Clinical Study for the Treatment of Cold Sore

Study Overview
=================
Brief Summary
-----------------
To demonstrate the efficacy of a single dose of acyclovir Lauriad® 50mg muco-adhesive buccal tablet versus a single dose of matching placebo on the primary vesicular lesion of cold sore.

Official Title
-----------------
A Randomised, Double-Blind, Single Dose, One-Day Early Administration, Multicentre Study Comparing the Efficacy and Safety of Acyclovir Lauriad® 50 mg Muco-adhesive Buccal Tablet to Matching Placebo, in the Treatment of Herpes Labialis in Immunocompetent Patients.

Conditions
-----------------
Herpes Labialis

Intervention / Treatment
-----------------
* Drug: Acyclovir Lauriad
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: History of recurrent herpes labialis lesions where: At least 50% of previous episodes produced classical lesions to the vesicular stage (i.e. episodes that progressed through macula, papule, vesicle, crust and healed); Prodromal symptoms (itching, tingling, pain etc.) should precede herpes labialis lesions in at least 50% of the previous herpes episodes Good general health (ECOG < 2), immunocompetent Signed and dated written informed consent Women of childbearing potential must have effective contraception method Exclusion Criteria: More than 50% of recurrences that aborted spontaneously in the past 12 months Primary herpes lesion outside the lips (e.g. nose, chin, etc.) Abnormal peri-oral skin condition that might affect the normal course of cold sores (e.g. eczema, psoriasis…) Oral diseases whose prodromal symptoms may mimick those of herpes labialis, including recurrent oral aphthous disease Oral diseases that might interfere with the evaluation of the efficacy or safety of the treatments, including gingivitis, parondotis, mucositis, oropharyngeal candidiasis… History of infection known to be resistant to acyclovir family agents Previous vaccination against herpes Concomitant treatment likely to interfere with acyclovir Allergy to any acyclovir containing agents Immunocompromised condition, including HIV+ Unability to properly understand protocol requirements, to follow the study procedures, to complete the patient diary or to start the self-initiation of the treatment Upper full or partial dentures with acrylic border in the canine fossa Milk allergy or known history of hypersensitivity to one of the components of the products Rare hereditary problems of galactose intolerance. Lactase enzyme deficiency or glucose galactose malabsorption Clinically significant abnormal level of serum creatinine Patients whose occupations make them unlikely to return to the clinic within 24h of treatment initiation Pregnancy or breast-feeding Investigational drug or immunomodulator treatment in the 30 days prior randomisation Prior enrollment in this study Participation in another therapeutic trial evaluating new drugs or which could interfere with the evolution of herpes labialis or the evaluation of the drug in the study within preceding 30 day.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Acyclovir Lauriad 50mg | Drug: Acyclovir Lauriad<br>* 50 mg muco-adhesive buccal tablets, single application on the gum<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* 50 mg muco-adhesive buccal tablets, single application on the gum<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Healing (TTH) of Vesicular Primary Lesion | Healing was defined as the loss of crust (erythema may be present) as assessed by the investigator. TTH was the time from treatment initiation to healing as defined above and was assessed from the time of treatment initiation through Day 14. The primary vesicular lesion was the first developed lesion located on the lip and was not to have extended more than 1 cm outside the lip. | Assessed from time of treatment initiation through Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abortion of Primary Lesions | Aborted lesions were defined as herpetic lesions preceded by prodromal symptoms that did not progress beyond the papule stage. | Assessed from the time of treatment initiation through Day 14 | 
| TTH of Non-primary Lesions (Aborted Lesions Excluded) | TTH of non-primary lesions was defined as the time from treatment initiation to healing of all non-primary vesicular lesions. Non-primary lesions were those that developed in addition to and/or in 1 or more days after the primary vesicular lesion and that were located at least 1 cm from the primary lesion. Aborted lesions were not included in this parameter. TTH was to be assessed by the investigator. | Assessed from the time of treatment initiation through Day 14 | 
| Duration of Episode (DOE) | For patients who experienced a vesicular lesion, DOE was defined as the time from treatment initiation to healing of primary and secondary vesicular lesions (loss of crust). For subjects whose primary and secondary lesions were not vesicular in nature, DOE was defied as the time from treatment initiation to return to normal skin or to cessation of symptoms, whichever came last. | Assessed from initiation of treatment to Day 14 | 
| Time to Cessation of Symptoms | Time to cessation of symptoms was defined as the time from treatment initiation to cessation of all symptoms: pain, burning, itching, tingling, tenderness and discomfort. It was to be assessed by the investigator. | Assessed from time of treatment initiation through Day 14 | 
| TTH of Aborted Primary Lesions | TTH of aborted primary lesions was defined as the time from treatment initiation to healing of the primary lesion (erythema or papule) or cessation of symptoms, whichever came last. It was to be assessed by the investigator. | Assessed from time of treatment initiation through Day 14 | 
| Time to Recurrence of Non-aborted Lesions During 9-month Follow-up | Time to recurrence was the time from the healing of all lesions of the initial episode to the occurrence of new lesions. | From time of initial healing through the 9-month follow-up | 
| Patient Incidence of Recurrence of Non-aborted Lesions During 9-month Follow-up | Recurrence was the occurrence of new lesions and was evaluated in a subgroup of patients who agreed to record recurrences during the 9-month follow-up period. | From time of initial healing through the 9-month follow-up | 
| Symptom Intensity (Visual Analogue Scale [VAS]) | Patients were asked to place a tick mark on a 10 centimeter VAS indicating their symptom intensity. Scale ratings ranged from a minimum of 0 (none at all) to a maximum of 10 (worst possible). The location of the tick mark from 0 was measured in millimeters (0 - 100) and recorded. | Assessed on Days 1, 3, 5, 7 and 14 (or within 24 hours of healing) | 
| Patient Satisfaction With Treatment | At the end of study (Day 14 [or within 24 hours of healing]), patients were asked whether they were satisfied with treatment (yes/no). | Assessed on Day 14 (or within 24 hours of healing) | 
| Patient Assessment of Efficacy of the Treatment | At the end of study (Day 14 [ or within 24 hours of healing]), patients were asked to rate efficacy of treatment using a 4-point scale (inactive, mildly active, moderately active, or very active). | Assessed on Day 14 (or within 24 hours of healing) |