Trial Outcomes & Findings for Phase 3 Clinical Study for the Treatment of Cold Sore (NCT NCT00769314)
NCT ID: NCT00769314
Last Updated: 2012-12-21
Results Overview
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.
COMPLETED
PHASE3
1727 participants
Assessed from time of treatment initiation through Day 14
2012-12-21
Participant Flow
Patients were screened beginning March 2007 and the last patient was treated in October 2008. The study was conducted at 47 sites in Australia, the Czech Republic, France, Germany, Poland, the United Kingdom and the United States.
Per protocol, a total of 1950 patients were to be randomized. Following randomization, patients were not to start treatment until a new labial herpes episode occurred. Thus, of those randomized, only 780 patients were planned to be treated (390 patients per treatment group) and 1170 patients were to be randomized, but not treated.
Participant milestones
| Measure |
Acyclovir Lauriad Group
Acyclovir Lauriad 50mg muco-adhesive tablet
|
Placebo Group
muco-adhesive buccal tablet with placebo
|
|---|---|---|
|
Overall Study
STARTED
|
378
|
397
|
|
Overall Study
COMPLETED
|
361
|
384
|
|
Overall Study
NOT COMPLETED
|
17
|
13
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase 3 Clinical Study for the Treatment of Cold Sore
Baseline characteristics by cohort
| Measure |
Acyclovir Lauriad Group
n=376 Participants
Acyclovir Lauriad 50mg muco-adhesive tablet/Intent-to-Treat population
|
Placebo Group
n=395 Participants
muco-adhesive buccal tablet with placebo/Intent-to-Treat population
|
Total
n=771 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
40 years
STANDARD_DEVIATION 12.97 • n=5 Participants
|
41.9 years
STANDARD_DEVIATION 13.33 • n=7 Participants
|
41.0 years
STANDARD_DEVIATION 13.18 • n=5 Participants
|
|
Sex: Female, Male
Female
|
258 Participants
n=5 Participants
|
271 Participants
n=7 Participants
|
529 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
118 Participants
n=5 Participants
|
124 Participants
n=7 Participants
|
242 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
71 participants
n=5 Participants
|
72 participants
n=7 Participants
|
143 participants
n=5 Participants
|
|
Region of Enrollment
France
|
41 participants
n=5 Participants
|
49 participants
n=7 Participants
|
90 participants
n=5 Participants
|
|
Region of Enrollment
Czech Republic
|
47 participants
n=5 Participants
|
50 participants
n=7 Participants
|
97 participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
74 participants
n=5 Participants
|
70 participants
n=7 Participants
|
144 participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
53 participants
n=5 Participants
|
68 participants
n=7 Participants
|
121 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
79 participants
n=5 Participants
|
77 participants
n=7 Participants
|
156 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
11 participants
n=5 Participants
|
9 participants
n=7 Participants
|
20 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Assessed from time of treatment initiation through Day 14Population: The modified Intent-to-Treat (mITT) population was the population used for analysis of this endpoint. The mITT population included all randomized patients who received at least one dose of study medication and who reached the vesicular stage (ie, episodes that progressed through macula, papule, vesicle, crust and healing).
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.
Outcome measures
| Measure |
Acyclovir Lauriad Group
n=242 Participants
Acyclovir Lauriad 50mg muco-adhesive tablet
|
Placebo Group
n=279 Participants
muco-adhesive buccal tablet with placebo
|
|---|---|---|
|
Time to Healing (TTH) of Vesicular Primary Lesion
|
7.00 Days
95% Confidence Interval 0.18 • Interval 6.75 to 7.31
|
7.32 Days
95% Confidence Interval 0.18 • Interval 6.97 to 7.92
|
SECONDARY outcome
Timeframe: Assessed from the time of treatment initiation through Day 14Population: This endpoint was analyzed using the Intent-to-Treat (ITT) population, which consisted of all randomized patients who received at least one dose of study medication and who had complete information recorded for the application time.
Aborted lesions were defined as herpetic lesions preceded by prodromal symptoms that did not progress beyond the papule stage.
Outcome measures
| Measure |
Acyclovir Lauriad Group
n=376 Participants
Acyclovir Lauriad 50mg muco-adhesive tablet
|
Placebo Group
n=395 Participants
muco-adhesive buccal tablet with placebo
|
|---|---|---|
|
Abortion of Primary Lesions
Aborted Lesions = Yes
|
130 participants
|
109 participants
|
|
Abortion of Primary Lesions
Aborted Lesions = No
|
242 participants
|
279 participants
|
|
Abortion of Primary Lesions
Aborted Lesions = Missing
|
4 participants
|
7 participants
|
SECONDARY outcome
Timeframe: Assessed from the time of treatment initiation through Day 14Population: This endpoint was analyzed using a subgroup of patients in the ITT population with non-primary lesions.
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.
Outcome measures
| Measure |
Acyclovir Lauriad Group
n=39 Participants
Acyclovir Lauriad 50mg muco-adhesive tablet
|
Placebo Group
n=62 Participants
muco-adhesive buccal tablet with placebo
|
|---|---|---|
|
TTH of Non-primary Lesions (Aborted Lesions Excluded)
|
7.00 Days
Interval 5.53 to 8.7
|
9.08 Days
Interval 7.46 to 11.0
|
SECONDARY outcome
Timeframe: Assessed from initiation of treatment to Day 14Population: This endpoint was analyzed using the ITT population.
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.
Outcome measures
| Measure |
Acyclovir Lauriad Group
n=373 Participants
Acyclovir Lauriad 50mg muco-adhesive tablet
|
Placebo Group
n=395 Participants
muco-adhesive buccal tablet with placebo
|
|---|---|---|
|
Duration of Episode (DOE)
|
5.57 Days
Interval 5.03 to 6.01
|
6.38 Days
Interval 5.93 to 6.97
|
SECONDARY outcome
Timeframe: Assessed from time of treatment initiation through Day 14Population: This endpoint was analyzed using the ITT population.
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.
Outcome measures
| Measure |
Acyclovir Lauriad Group
n=373 Participants
Acyclovir Lauriad 50mg muco-adhesive tablet
|
Placebo Group
n=393 Participants
muco-adhesive buccal tablet with placebo
|
|---|---|---|
|
Time to Cessation of Symptoms
|
3.57 Days
Interval 3.04 to 4.01
|
4.16 Days
Interval 3.75 to 4.89
|
SECONDARY outcome
Timeframe: Assessed from time of treatment initiation through Day 14Population: This endpoint was analyzed using the subgroup of patients within the ITT population with aborted 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.
Outcome measures
| Measure |
Acyclovir Lauriad Group
n=108 Participants
Acyclovir Lauriad 50mg muco-adhesive tablet
|
Placebo Group
n=85 Participants
muco-adhesive buccal tablet with placebo
|
|---|---|---|
|
TTH of Aborted Primary Lesions
|
2.57 Days
Interval 2.0 to 2.96
|
2.67 Days
Interval 2.1 to 3.04
|
SECONDARY outcome
Timeframe: From time of initial healing through the 9-month follow-upPopulation: This endpoint was analyzed using the follow-up population, a subgroup of the ITT population who continued to the 9 month follow-up and had at least 1 diary assessment during that period. The follow-up population was defined as patients whose lesions were healed at the end of Day 14 and had no recurrence within 15 days of healing of all lesions.
Time to recurrence was the time from the healing of all lesions of the initial episode to the occurrence of new lesions.
Outcome measures
| Measure |
Acyclovir Lauriad Group
n=232 Participants
Acyclovir Lauriad 50mg muco-adhesive tablet
|
Placebo Group
n=246 Participants
muco-adhesive buccal tablet with placebo
|
|---|---|---|
|
Time to Recurrence of Non-aborted Lesions During 9-month Follow-up
|
205.0 Days
95% Confidence Interval 19.4 • Interval 163.0 to 287.0
|
165.0 Days
95% Confidence Interval 9.3 • Interval 136.0 to 203.0
|
SECONDARY outcome
Timeframe: From time of initial healing through the 9-month follow-upPopulation: This endpoint was analyzed using the follow-up population, a subgroup of the ITT population who continued to the 9 month follow-up and had at least 1 diary assessment during that period. The follow-up population was defined as patients whose lesions were healed at the end of Day 14 and had no recurrence within 15 days of healing of all lesions.
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.
Outcome measures
| Measure |
Acyclovir Lauriad Group
n=267 Participants
Acyclovir Lauriad 50mg muco-adhesive tablet
|
Placebo Group
n=270 Participants
muco-adhesive buccal tablet with placebo
|
|---|---|---|
|
Patient Incidence of Recurrence of Non-aborted Lesions During 9-month Follow-up
Recurrence during 9-month follow-up = yes
|
149 participants
|
181 participants
|
|
Patient Incidence of Recurrence of Non-aborted Lesions During 9-month Follow-up
Recurrence during 9-month follow-up = no
|
83 participants
|
65 participants
|
|
Patient Incidence of Recurrence of Non-aborted Lesions During 9-month Follow-up
Recurrence during 9-month follow-up = missing
|
35 participants
|
24 participants
|
SECONDARY outcome
Timeframe: Assessed on Days 1, 3, 5, 7 and 14 (or within 24 hours of healing)Population: This endpoint was analyzed using the safety population, which consisted of all randomized patients who took at least 1 dose of study medication.
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.
Outcome measures
| Measure |
Acyclovir Lauriad Group
n=378 Participants
Acyclovir Lauriad 50mg muco-adhesive tablet
|
Placebo Group
n=397 Participants
muco-adhesive buccal tablet with placebo
|
|---|---|---|
|
Symptom Intensity (Visual Analogue Scale [VAS])
Day 1
|
30.5 units on a scale (0 - 100)
Standard Deviation 22.37
|
31.1 units on a scale (0 - 100)
Standard Deviation 22.07
|
|
Symptom Intensity (Visual Analogue Scale [VAS])
Day 3
|
21.2 units on a scale (0 - 100)
Standard Deviation 22.88
|
22.9 units on a scale (0 - 100)
Standard Deviation 22.60
|
|
Symptom Intensity (Visual Analogue Scale [VAS])
Day 5
|
12.7 units on a scale (0 - 100)
Standard Deviation 17.60
|
17.3 units on a scale (0 - 100)
Standard Deviation 20.70
|
|
Symptom Intensity (Visual Analogue Scale [VAS])
Day 7
|
8.2 units on a scale (0 - 100)
Standard Deviation 13.63
|
10.7 units on a scale (0 - 100)
Standard Deviation 18.48
|
|
Symptom Intensity (Visual Analogue Scale [VAS])
Day 14 (or within 24 hours of healing)
|
1.0 units on a scale (0 - 100)
Standard Deviation 5.14
|
0.9 units on a scale (0 - 100)
Standard Deviation 3.61
|
SECONDARY outcome
Timeframe: Assessed on Day 14 (or within 24 hours of healing)Population: This endpoint was analyzed using the ITT population.
At the end of study (Day 14 \[or within 24 hours of healing\]), patients were asked whether they were satisfied with treatment (yes/no).
Outcome measures
| Measure |
Acyclovir Lauriad Group
n=376 Participants
Acyclovir Lauriad 50mg muco-adhesive tablet
|
Placebo Group
n=395 Participants
muco-adhesive buccal tablet with placebo
|
|---|---|---|
|
Patient Satisfaction With Treatment
Satisfied with treatment = yes
|
297 participants
|
275 participants
|
|
Patient Satisfaction With Treatment
Satisfied with treatment = no
|
66 participants
|
105 participants
|
|
Patient Satisfaction With Treatment
Missing
|
13 participants
|
15 participants
|
SECONDARY outcome
Timeframe: Assessed on Day 14 (or within 24 hours of healing)Population: This endpoint was analyzed using the ITT population.
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).
Outcome measures
| Measure |
Acyclovir Lauriad Group
n=376 Participants
Acyclovir Lauriad 50mg muco-adhesive tablet
|
Placebo Group
n=395 Participants
muco-adhesive buccal tablet with placebo
|
|---|---|---|
|
Patient Assessment of Efficacy of the Treatment
Inactive
|
50 participants
|
79 participants
|
|
Patient Assessment of Efficacy of the Treatment
Midly active
|
49 participants
|
44 participants
|
|
Patient Assessment of Efficacy of the Treatment
Moderately active
|
100 participants
|
104 participants
|
|
Patient Assessment of Efficacy of the Treatment
Very active
|
154 participants
|
146 participants
|
|
Patient Assessment of Efficacy of the Treatment
Missing
|
23 participants
|
22 participants
|
Adverse Events
Acyclovir Lauriad Group
Placebo Group
Serious adverse events
| Measure |
Acyclovir Lauriad Group
n=378 participants at risk
Acyclovir Lauriad 50mg muco-adhesive tablet
|
Placebo Group
n=397 participants at risk
muco-adhesive buccal tablet with placebo
|
|---|---|---|
|
Immune system disorders
Allergic reaction
|
0.00%
0/378 • Adverse events were recorded during the 14 day treatment period.
The safety population included all randomized patients who took at least 1 dose of study drug, including 378 patients in the acyclovir Lauriad group and 397 patients in the placebo group.
|
0.25%
1/397 • Number of events 1 • Adverse events were recorded during the 14 day treatment period.
The safety population included all randomized patients who took at least 1 dose of study drug, including 378 patients in the acyclovir Lauriad group and 397 patients in the placebo group.
|
Other adverse events
| Measure |
Acyclovir Lauriad Group
n=378 participants at risk
Acyclovir Lauriad 50mg muco-adhesive tablet
|
Placebo Group
n=397 participants at risk
muco-adhesive buccal tablet with placebo
|
|---|---|---|
|
Nervous system disorders
headache
|
3.2%
12/378 • Number of events 12 • Adverse events were recorded during the 14 day treatment period.
The safety population included all randomized patients who took at least 1 dose of study drug, including 378 patients in the acyclovir Lauriad group and 397 patients in the placebo group.
|
3.0%
12/397 • Number of events 12 • Adverse events were recorded during the 14 day treatment period.
The safety population included all randomized patients who took at least 1 dose of study drug, including 378 patients in the acyclovir Lauriad group and 397 patients in the placebo group.
|
|
Infections and infestations
Nasopharyngitis
|
1.1%
4/378 • Number of events 4 • Adverse events were recorded during the 14 day treatment period.
The safety population included all randomized patients who took at least 1 dose of study drug, including 378 patients in the acyclovir Lauriad group and 397 patients in the placebo group.
|
0.76%
3/397 • Number of events 3 • Adverse events were recorded during the 14 day treatment period.
The safety population included all randomized patients who took at least 1 dose of study drug, including 378 patients in the acyclovir Lauriad group and 397 patients in the placebo group.
|
|
General disorders
Application Site Pain
|
1.1%
4/378 • Number of events 4 • Adverse events were recorded during the 14 day treatment period.
The safety population included all randomized patients who took at least 1 dose of study drug, including 378 patients in the acyclovir Lauriad group and 397 patients in the placebo group.
|
1.0%
4/397 • Number of events 4 • Adverse events were recorded during the 14 day treatment period.
The safety population included all randomized patients who took at least 1 dose of study drug, including 378 patients in the acyclovir Lauriad group and 397 patients in the placebo group.
|
|
Gastrointestinal disorders
nausea
|
0.26%
1/378 • Number of events 1 • Adverse events were recorded during the 14 day treatment period.
The safety population included all randomized patients who took at least 1 dose of study drug, including 378 patients in the acyclovir Lauriad group and 397 patients in the placebo group.
|
1.5%
6/397 • Number of events 6 • Adverse events were recorded during the 14 day treatment period.
The safety population included all randomized patients who took at least 1 dose of study drug, including 378 patients in the acyclovir Lauriad group and 397 patients in the placebo group.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60