Phase 3 Clinical Study for the Treatment of Cold Sore (LIP)

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.

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.

Study Overview

• Status: Completed
• Conditions: Herpes Labialis
• Intervention / Treatment: Drug: Acyclovir Lauriad; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1727
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Sydney, Australia, Darlinghurst, NSW 2010
    • Taylor Square Private Clinic
  • Sydney, Australia, QLD 4006
    • Central Brunswick Medical Centre
• Czech Republic
  • Opava, Czech Republic, 128 08 Praha 2
    • General Teaching Hospital, Dep. Of Dermatology
  • Opava, Czech Republic, 747 00
    • U zastavky 16
  • Praha, Czech Republic, 169 02 Praha 6
    • Central military hospital Dept. of Dermatology
  • Praha, Czech Republic, 180 81 Praha 8
    • University Hospital Bulovka 3rd Clinic of Inf. Diseases
  • Praha, Czech Republic, 180 81 Praha 8
    • University Hospital Bulovka Dept. of Dermatology
• France
  • Besancon, France, 25030 BESANCON CEDEX
    • Hôpital St Jacques Service de Dermatologie
  • Martigues, France, 13500
    • Private Practice
  • Nancy, France, 54000
    • Hopital Fournier, Service de dermatologie
  • Nice, France, 06000
    • Private Practice
  • Nice, France, 06202 NICE Cedex
    • Hôpital L'Archet 2, Service de Dermatologie
  • Paris, France, 75005
    • Private Practice
  • Paris, France, 75020
    • Hôpital Tenon, Dermatology department
  • Paris, France, 75475 PARIS Cedex 10
    • Hôpital Saint Louis Paris, Service de Dermatologie 1
  • Paris, France, 75651 Paris Cedex 13
    • Service de Stomatologie et chirurgie Maxilo-Faciale.Hôpital de la pitié Salpétrière
  • St. Etienne, France, 42065 St ETIENNE Cedex 2
    • Hôpital Nord, Service de Dermatologie
  • Tours, France, 37044 TOURS Cedex
    • Hôpital Trousseau
• Germany
  • Augsburg, Germany, 86153
    • Praxis Dres. Dörzapf und Partner
  • Berlin, Germany, 12157
    • POLIKUM Friedenau
  • Berlin, Germany, 10117
    • Charité Universitätsmedizin Berlin Klinik für Dermatologie, Venerologie und Allergologie
  • Berlin, Germany, 10789
    • Praxis
  • Berlin, Germany, 12353
    • Gemeinschaftspraxis
  • Biberach, Germany, 88400
    • Laserclinic Drs. Steinert
  • Bonn, Germany, 53105
    • Klinik und Poliklinik für Dermatologie des Universitätsklinikums Bonn
  • Frankfurt, Germany, 60326
    • Praxis
  • Oberkirch, Germany, 77704
    • Raiffeisenstr. 15b
  • Rodgau-Dudenhofen, Germany
    • Ludwig-Erhard-Platz 9-11
• Poland
  • Bydgoszcz, Poland, 85-096
    • Katedra i Klinika Dermatologii Collegium Medicum
  • Chrzanów, Poland, 32-500
    • Centrum Medyczne Diabet
  • Gdynia, Poland, 81-366
    • Naukowo-Badawczy i Naukowo-Dydaktyczny Ośrodek Dermatologii Estetycznej, Dermatochirurgii i Fotodermatologii
  • Grudziądz, Poland, 86-300
    • Niepubliczny Zaklad Opieki Zdrowotnej GCP Dobra Praktyka Lekarska
  • Kraków, Poland, 31-159
    • NZOZ Atopia, Al. J.
  • Płock, Poland, 09-402
    • Niepubliczny Zakład Opieki Zdrowotnej Specjalistyczna Przychodnia Lekarska Medikard
  • Toruń, Poland, 87-100
    • Niepubliczny Zakład Opieki Zdrowotnej "Nasz Lekarz" Praktyka Grupowa Lekarzy Rodzinnych z Przychodnią Specjalistyczną
  • Warszawa, Poland, 03-003
    • Gabinet Internistyczny
  • Wrocław, Poland, 50-354
    • NZOZ Praktyka Lekarska Iga Gilas - Mirkiewicz
  • Łódź, Poland, 90-265
    • Specjalistyczne Gabinety Lekarskie DERMED
• United Kingdom
  • Canterbury, United Kingdom, CT1 3HX
    • Cossington House Surgery
  • Cardiff, United Kingdom, CF14 4XN
    • School of Dentistry, Cardiff University
  • East Sussex, United Kingdom, TN40 1JJ
    • Sea Road Surgery
  • East Sussex, United Kingdom, TN39 5HE
    • Sidley Surgery
  • Saltash, United Kingdom, PL12 6DL
    • Saltash Health Centre
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Radiant Research, Inc.,
    • Tucson, Arizona, United States, 85710
      • Radiant Research, Inc.,
  • California
    • San Fransisco, California, United States, 94114
      • Dermatology Private Practice
  • Colorado
    • Wheat Ridge, Colorado, United States, 80033
      • Front Range Clinical Research
  • Idaho
    • Meridian, Idaho, United States, 83642
      • St. Luke's Family Health,
  • Missouri
    • Springfield, Missouri, United States, 65807
      • Clinvest, a Division of Banyan Group, Inc.,
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.,
    • Stony Brook, New York, United States, 11794-8091
      • Stony Brook University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Center for Clinical Studies
    • Houston, Texas, United States, 77058
      • Center for Clinical Studies, Ltd., LLP.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: 2	Drug: Placebo; 50 mg muco-adhesive buccal tablets, single application on the gum
EXPERIMENTAL: 1; Acyclovir Lauriad 50mg	Drug: Acyclovir Lauriad; 50 mg muco-adhesive buccal tablets, single application on the gum

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)

Collaborators and Investigators

• Sponsor: Onxeo

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (ACTUAL): November 1, 2008
• Study Completion (ACTUAL): August 1, 2009

Study Registration Dates

• First Submitted: October 8, 2008
• First Submitted That Met QC Criteria: October 8, 2008
• First Posted (ESTIMATE): October 9, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): December 21, 2012
• Last Update Submitted That Met QC Criteria: November 21, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Virus Diseases; Infections; Stomatognathic Diseases; Mouth Diseases; DNA Virus Infections; Skin Diseases, Infectious; Skin Diseases, Viral; Herpesviridae Infections; Lip Diseases; Herpes Simplex; Herpes Labialis; Anti-Infective Agents; Antiviral Agents; Acyclovir
• Other Study ID Numbers: BA2005/21/02