An Exploratory Study to Investigate the Inflammatory Response During a Cold Sore Episode

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01653509
• Collaborator: Labtec GmbH (Industry)
• Enrollment: 60
• Location: 1
• Arms: 2
• Duration (Months): 2
• Patients Per Site Per Month: 29.5

Study Details

Study Description

Brief Summary

This study will treat approximately 24 participants who experience cold sores. Patches will be applied to the cold sore for up to ten days, and the symptoms will be measured during daily clinic visits using non-invasive measurement techniques.

Condition or Disease	Intervention/Treatment	Phase
Herpes Labialis	Device: Acyclovir patch; Device: Placebo patch	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: An Exploratory Study to Investigate the Inflammatory Response During a Cold Sore Episode
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Test patch Patch containing acyclovir applied to cold sore	Device: Acyclovir patch; Patch containing acyclovir
Placebo Comparator: Placebo patch Patch without acyclovir applied to cold sore	Device: Placebo patch; Patch without acyclovir

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in Blood Flow [Baseline to Day 10]

   Measurement of blood flow was performed using Field Laser Perfusion Imaging (FLPI) technique. Total episode value (TEV) was calculated as the summation of (test region response minus control region response) across all days. Maximum episode value (MEV) was calculated as the maximum of (test region response minus control region response) across all days.

2. Mean Change From Baseline in Temperature [Baseline to Day 10]

   Lesion thermographic parameters for TEV and MEV were analysed.

3. Mean Change From Baseline in Color Intensity of Lesions [Baseline to Day 10]

   The redness of the cold sores to be measured and quantified using sophisticated, standardized and reproducible color photography. Parameter represents distance between test and control values according to a* axis and b* axis colour intensity values. The values on the scale ranged from -100 (green, lowest intensity) to +100 (red, highest intensity).

Secondary Outcome Measures

1. Participant Assessment of Patch Comfort and Noticeability at Day 5 [Day 5]

   Participants reported experience of the patch aesthetics and cold sore noticeability on the cold sore using a 5-point scale ( 1=Strongly Disagree 2=Rather Disagree 3=Neither Agree nor Disagree 4=Mostly Agree 5=Completely Agree) on 9 questions asked to them: Today my sore felt completely protected Today my cold sores interfered with facial movements such as smiling, eating or drinking Today my cold sores interfered with my interaction with other people Today the patch disguised my cold sores Today I was bothered by the appearance of my cold sores Today my patch was easy to apply Today the patch covering my cold sores was bothersome Today the patches stayed in place on my cold sores until I removed them Today the patches were easy to remove from my lip or skin

2. Participant Assessment of Patch Comfort and Noticeability at Day 10 [Day 10]

   Participants reported experience of the patch aesthetics and cold sore noticeability on the cold sore using a 5-point scale ( 1=Strongly Disagree 2=Rather Disagree 3=Neither Agree nor Disagree 4=Mostly Agree 5=Completely Agree) on 9 questions asked to them: Today my sore felt completely protected Today my cold sores interfered with facial movements such as smiling, eating or drinking Today my cold sores interfered with my interaction with other people Today the patch disguised my cold sores Today I was bothered by the appearance of my cold sores Today my patch was easy to apply Today the patch covering my cold sores was bothersome Today the patches stayed in place on my cold sores until I removed them Today the patches were easy to remove from my lip or skin

3. Participant Assessment of Symptom Intensity at Day 5 [Day 5]

   Cold sore symptoms (pain, burning, itching) assessment was evaluated on a 5-point scale: 1=Never Bothered, 2=Rarely Bothered, 3=Bothered Some of the Time, 4=Bothered Often, 5=Bothered All the Time.

4. Participant Assessment of Symptom Intensity at Day 10 [Day 10]

   Cold sore symptoms (pain, burning, itching) assessment was performed on a 5-point scale: 1=Never Bothered 2=Rarely Bothered 3=Bothered Some of the Time 4=Bothered Often 5=Bothered All the Time.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Participants who are susceptible to cold sores that reactivate when exposed to ultraviolet (UV) light

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	proDERM Institute for Applied Dermatological Research GmbH	Hamburg		Germany	22869

Sponsors and Collaborators

• GlaxoSmithKline
• Labtec GmbH

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01653509
• Other Study ID Numbers: E7411153
• First Posted: Jul 31, 2012
• Last Update Posted: Jul 16, 2014
• Last Verified: Feb 1, 2014

• Keywords provided by GlaxoSmithKline: cold sore
• Additional relevant MeSH terms: Herpes Labialis; Acyclovir

Study Results

Participant Flow

Recruitment Details	Participants were recruited at the clinical site.
Pre-assignment Detail	105 screened, 60 underwent ultraviolet (UV) rays induction, 25 developed a cold sore and were randomized into the study.

Arm/Group Title	Acyclovir Patch	Placebo Patch
Arm/Group Description	Participants applied single patch containing acyclovir to the cold sore area. A maximum of 5 patches/ day were allowed during the 10 day study period.	Participants applied single placebo patch to the cold sore area. A maximum of 5 patches/ day were allowed during the 10 day study period.
Period Title: Overall Study
STARTED	12	13
COMPLETED	12	13
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Acyclovir Patch	Placebo Patch	Total
Arm/Group Description	Participants applied single patch containing acyclovir to the cold sore area. A maximum of 5 patches/ day were allowed during the 10 day study period. Baseline measures were determined for Safety population.	Participants applied single placebo patch to the cold sore area. A maximum of 5 patches/ day were allowed during the 10 day study period. Baseline measures were determined for Safety population.	Total of all reporting groups
Overall Participants	12	13	25
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	47.6 (14.88)	43.2 (15.60)	45.3 (15.11)
Sex: Female, Male (Count of Participants)
Female	11 91.7%	12 92.3%	23 92%
Male	1 8.3%	1 7.7%	2 8%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in Blood Flow
Description	Measurement of blood flow was performed using Field Laser Perfusion Imaging (FLPI) technique. Total episode value (TEV) was calculated as the summation of (test region response minus control region response) across all days. Maximum episode value (MEV) was calculated as the maximum of (test region response minus control region response) across all days.
Time Frame	Baseline to Day 10

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) population: all randomized participants who had a patch applied to their cold sore and have at least one post-baseline efficacy measurement.

Arm/Group Title	Acyclovir Patch	Placebo Patch
Arm/Group Description	Participants applied single patch containing acyclovir to the cold sore area. A maximum of 5 patches/ day were allowed during the 10 day study period.	Participants applied single placebo patch to the cold sore area. A maximum of 5 patches/ day were allowed during the 10 day study period.
Measure Participants	12	13
TEV (Day 1 to Day 10)	2558.65 (627.87)	3470.13 (603.23)
MEV	809.88 (127.93)	960.86 (122.91)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Acyclovir Patch, Placebo Patch
	Comments	Null hypothesis considered no difference between study treatments for TEV.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3061
	Comments
	Method	ANOVA
	Comments	ANOVA model with a factor for treatment group.
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-911.48
	Confidence Interval	(2-Sided) 95%; -2712.65 to 889.69
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference calculated as first named treatment minus second named treatment, such that a negative difference favours the first named treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Acyclovir Patch, Placebo Patch
	Comments	Null hypothesis considered no difference between treatments for MEV.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4035
	Comments
	Method	ANOVA
	Comments	ANOVA model with a factor for treatment group.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-150.99
	Confidence Interval	(2-Sided) 95%; -517.97 to 215.99
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference calculated as first named treatment minus second named treatment, such that a negative difference favours the first named treatment.

2. Primary Outcome

Title	Mean Change From Baseline in Temperature
Description	Lesion thermographic parameters for TEV and MEV were analysed.
Time Frame	Baseline to Day 10

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants who had a patch applied to their cold sore and have at least one post-baseline efficacy measurement.

Arm/Group Title	Acyclovir Patch	Placebo Patch
Arm/Group Description	Participants applied single patch containing acyclovir to the cold sore area. A maximum of 5 patches/ day were allowed during the 10 day study period.	Participants applied single placebo patch to the cold sore area. A maximum of 5 patches/ day were allowed during the 10 day study period.
Measure Participants	12	13
TEV (Day 1 to Day 10)	3.24 (0.86)	0.76 (0.82)
MEV	0.90 (0.15)	0.51 (0.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Acyclovir Patch, Placebo Patch
	Comments	Null hypothesis considered no difference between study treatments for TEV (Day 1 to day 10).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0486
	Comments
	Method	ANOVA
	Comments	ANOVA model with a factor for treatment group.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.48
	Confidence Interval	(2-Sided) 95%; 0.02 to 4.93
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference calculated as first named treatment minus second named treatment, such that a negative difference favours the first named treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Acyclovir Patch, Placebo Patch
	Comments	Null hypothesis considered no difference between study treatments for MEV.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0799
	Comments
	Method	ANOVA
	Comments	ANOVA model with a factor for treatment group.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.38
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.82
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference calculated as first named treatment minus second named treatment, such that a negative difference favours the first named treatment.

3. Primary Outcome

Title	Mean Change From Baseline in Color Intensity of Lesions
Description	The redness of the cold sores to be measured and quantified using sophisticated, standardized and reproducible color photography. Parameter represents distance between test and control values according to a* axis and b* axis colour intensity values. The values on the scale ranged from -100 (green, lowest intensity) to +100 (red, highest intensity).
Time Frame	Baseline to Day 10

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants who had a patch applied to their cold sore and have at least one post-baseline efficacy measurement.

Arm/Group Title	Acyclovir Patch	Placebo Patch
Arm/Group Description	Participants applied single patch containing acyclovir to the cold sore area. A maximum of 5 patches/ day were allowed during the 10 day study period.	Participants applied single placebo patch to the cold sore area. A maximum of 5 patches/ day were allowed during the 10 day study period.
Measure Participants	12	13
TEV	11.05 (1.12)	8.91 (1.07)
MEV	2.66 (0.22)	2.29 (0.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Acyclovir Patch, Placebo Patch
	Comments	Null hypothesis considered no difference between study treatments for TEV.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1790
	Comments
	Method	ANOVA
	Comments	ANOVA model with a factor for treatment group.
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	2.14
	Confidence Interval	(2-Sided) 95%; -1.06 to 5.35
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference calculated as first named treatment minus second named treatment, such that a negative difference favours the first named treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Acyclovir Patch, Placebo Patch
	Comments	Null hypothesis considered no difference between study treatments for MEV.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2446
	Comments
	Method	ANOVA
	Comments	ANOVA model with a factor for treatment group.
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.37
	Confidence Interval	(2-Sided) 95%; -0.27 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference calculated as first named treatment minus second named treatment, such that a negative difference favours the first named treatment.

4. Secondary Outcome

Title	Participant Assessment of Patch Comfort and Noticeability at Day 5
Description	Participants reported experience of the patch aesthetics and cold sore noticeability on the cold sore using a 5-point scale ( 1=Strongly Disagree 2=Rather Disagree 3=Neither Agree nor Disagree 4=Mostly Agree 5=Completely Agree) on 9 questions asked to them: Today my sore felt completely protected Today my cold sores interfered with facial movements such as smiling, eating or drinking Today my cold sores interfered with my interaction with other people Today the patch disguised my cold sores Today I was bothered by the appearance of my cold sores Today my patch was easy to apply Today the patch covering my cold sores was bothersome Today the patches stayed in place on my cold sores until I removed them Today the patches were easy to remove from my lip or skin
Time Frame	Day 5

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants who had a patch applied to their cold sore and had at least one post-baseline efficacy measurement. There were difference in number of participants analyzed for each end point as represented by "n".

Arm/Group Title	Acyclovir Patch	Placebo Patch
Arm/Group Description	Participants applied single patch containing acyclovir to the cold sore area. A maximum of 5 patches/ day were allowed during the 10 day study period.	Participants applied single placebo patch to the cold sore area. A maximum of 5 patches/ day were allowed during the 10 day study period.
Measure Participants	12	13
Protection (n = 11, 12)	4.45 (0.69)	4.17 (1.12)
Facial Movements (n = 11, 12)	2.18 (1.33)	2.75 (1.60)
Interpersonal Interaction (n = 11, 12)	2.09 (1.45)	1.75 (0.97)
Cold Sore Cover (n = 11, 12)	4.45 (0.93)	3.92 (1.31)
Cold sore appearance (n = 11, 12)	1.55 (0.93)	1.67 (1.16)
Ease of application (n = 11, 12)	4.55 (0.69)	4.00 (1.04)
Bothersomeness (n = 11, 12)	1.55 (0.93)	1.55 (0.45)
Adhesivenes (n = 11, 12)	4.36 (0.92)	3.75 (0.97)
Patch removal (n = 9, 10)	4.33 (1.00)	4.60 (0.52)

5. Secondary Outcome

Title	Participant Assessment of Patch Comfort and Noticeability at Day 10
Description	Participants reported experience of the patch aesthetics and cold sore noticeability on the cold sore using a 5-point scale ( 1=Strongly Disagree 2=Rather Disagree 3=Neither Agree nor Disagree 4=Mostly Agree 5=Completely Agree) on 9 questions asked to them: Today my sore felt completely protected Today my cold sores interfered with facial movements such as smiling, eating or drinking Today my cold sores interfered with my interaction with other people Today the patch disguised my cold sores Today I was bothered by the appearance of my cold sores Today my patch was easy to apply Today the patch covering my cold sores was bothersome Today the patches stayed in place on my cold sores until I removed them Today the patches were easy to remove from my lip or skin
Time Frame	Day 10

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants who had a patch applied to their cold sore and have at least one post-baseline efficacy measurement. There were differences in number of participants analyzed for each end point as represented by "n".

Arm/Group Title	Acyclovir Patch	Placebo Patch
Arm/Group Description	Participants applied single patch containing acyclovir to the cold sore area. A maximum of 5 patches/ day were allowed during the 10 day study period.	Participants applied single placebo patch to the cold sore area. A maximum of 5 patches/ day were allowed during the 10 day study period.
Measure Participants	12	13
Protection (n= 4, 7)	4.50 (1.00)	4.14 (1.07)
Facial Movements (n= 4, 7)	1.50 (1.00)	2.29 (1.11)
Interpersonal Interaction (n= 4, 7)	1.50 (0.58)	1.14 (0.38)
Cold Sore Coverage (n= 4, 7)	4.75 (0.50)	4.57 (0.54)
Cold sore appearance (n= 4, 7)	1.50 (0.58)	1.14 (0.38)
Ease of application (n= 4, 7)	4.75 (0.50)	4.86 (0.38)
Bothersomeness (n= 4, 7)	1.50 (1.00)	2.43 (1.40)
Adhesiveness (n= 4, 7)	4.75 (0.50)	3.86 (1.35)
Patch removal (n = 3, 5)	4.33 (0.58)	4.60 (0.89)

6. Secondary Outcome

Title	Participant Assessment of Symptom Intensity at Day 5
Description	Cold sore symptoms (pain, burning, itching) assessment was evaluated on a 5-point scale: 1=Never Bothered, 2=Rarely Bothered, 3=Bothered Some of the Time, 4=Bothered Often, 5=Bothered All the Time.
Time Frame	Day 5

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants who had a patch applied to their cold sore and have at least one post-baseline efficacy measurement. There were differences in number of participants analyzed for each end point as represented by "n".

Arm/Group Title	Acyclovir Patch	Placebo Patch
Arm/Group Description	Participants applied single patch containing acyclovir to the cold sore area. A maximum of 5 patches/ day were allowed during the 10 day study period.	Participants applied single placebo patch to the cold sore area. A maximum of 5 patches/ day were allowed during the 10 day study period.
Measure Participants	12	13
Pain/Soreness (n = 11, 12)	1.55 (0.82)	1.75 (1.22)
Itching (n = 11, 12)	1.18 (0.41)	1.67 (0.99)
Burning (n = 11, 12)	1.36 (0.67)	1.42 (0.67)

7. Secondary Outcome

Title	Participant Assessment of Symptom Intensity at Day 10
Description	Cold sore symptoms (pain, burning, itching) assessment was performed on a 5-point scale: 1=Never Bothered 2=Rarely Bothered 3=Bothered Some of the Time 4=Bothered Often 5=Bothered All the Time.
Time Frame	Day 10

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants who had a patch applied to their cold sore and have at least one post-baseline efficacy measurement. There were differences in the number of participants analyzed for each end point, as represented by "n".

Arm/Group Title	Acyclovir Patch	Placebo Patch
Arm/Group Description	Participants applied single patch containing acyclovir to the cold sore area at a time. A maximum of 5 patches/ day were allowed during the 10 day study period.	Participants applied single placebo patch to the cold sore area at a time. A maximum of 5 patches/ day were allowed during the 10 day study period.
Measure Participants	12	13
Pain/Soreness (n = 4, 7)	1.00 (0.00)	1.29 (0.49)
Itching (n = 4, 7)	1.00 (0.00)	1.14 (0.38)
Burning (n = 4, 7)	1.00 (0.00)	1.00 (0.00)

Adverse Events

Time Frame	Adverse events were collected from UV exposure until the study completion assessments or the telephone follow-up for those participants not undergoing study completion assessments.
Arm/Group Title	Acyclovir Patch		Placebo Patch
Arm/Group Description	Participants applied single patch containing acyclovir to the cold sore area.		Participants applied single placebo patch to the cold sore area.
All Cause Mortality
	Acyclovir Patch		Placebo Patch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Acyclovir Patch		Placebo Patch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Acyclovir Patch		Placebo Patch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		3/13 (23.1%)
Gastrointestinal disorders
Lip Erosion	0/12 (0%)	0	1/13 (7.7%)	1
Infections and infestations
Oral Herpes	0/12 (0%)	0	1/13 (7.7%)	1
Skin and subcutaneous tissue disorders
Hyperkeratosis	0/12 (0%)	0	1/13 (7.7%)	1

Limitations/Caveats

The study was not formally powered to detect statistically significant differences, but to provide information for methods development and develop sample size calculation for future studies.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.