Trial Outcomes & Findings for A Study Comparing Daily Treatment With Valaciclovir To Placebo For Suppression Of Herpes Simplex Virus HSV-2 Genital Herpes In Newly Diagnosed Patients. VALTREX® Tablet is a Trademark of the GlaxoSmithKline Group of Companies. (NCT NCT00158860)
NCT ID: NCT00158860
Last Updated: 2019-02-15
Results Overview
Diary cards were issued to the participants during randomization visit for recording GH recurrences. HSV recurrences since the last visit was assessed after review of the diary card and discussion with the participant. The percentage of participants with time to first GH recurrence was based on Kaplan-Meier estimates. Confidence intervals for differences in proportions was calculated using the standard error for the Kaplan-Meier estimate derived using Greenwood's formula.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
384 participants
Primary outcome timeframe
Day 168
Results posted on
2019-02-15
Participant Flow
The study was conducted in 74 centers in the Unites States, Canada, Argentina, Brazil, and Chile.
A total of 384 participants with first recognized episode of genital herpes (GH) were randomized in this study, out of which one participant did not take the study medication, hence, the Intent-to-treat (ITT) population consisted of 383 participants.
Participant milestones
| Measure |
Placebo
Participants received double blinded treatment of oral dose of matching placebo to valacyclovir 1 gram (g) given as 2 x 500 milligram (mg) caplets once daily (QD) for 6 months (24 weeks). Participants with GH recurrences during the study temporarily discontinued their blinded treatment assignment and received open label valaciclovir 500 mg twice a day (BID) for 3 days after which the double-blind therapy was resumed.
|
Valaciclovir 1g QD
Participants received double blinded treatment of oral dose of Valacyclovir 1 g given as 2 x 500 mg caplets QD for 6 months (24 weeks). Participants with GH recurrences during the study temporarily discontinued their blinded treatment assignment and received open label valaciclovir 500 mg BID for 3 days after which the double-blind therapy was resumed.
|
|---|---|---|
|
Overall Study
STARTED
|
128
|
255
|
|
Overall Study
COMPLETED
|
93
|
184
|
|
Overall Study
NOT COMPLETED
|
35
|
71
|
Reasons for withdrawal
| Measure |
Placebo
Participants received double blinded treatment of oral dose of matching placebo to valacyclovir 1 gram (g) given as 2 x 500 milligram (mg) caplets once daily (QD) for 6 months (24 weeks). Participants with GH recurrences during the study temporarily discontinued their blinded treatment assignment and received open label valaciclovir 500 mg twice a day (BID) for 3 days after which the double-blind therapy was resumed.
|
Valaciclovir 1g QD
Participants received double blinded treatment of oral dose of Valacyclovir 1 g given as 2 x 500 mg caplets QD for 6 months (24 weeks). Participants with GH recurrences during the study temporarily discontinued their blinded treatment assignment and received open label valaciclovir 500 mg BID for 3 days after which the double-blind therapy was resumed.
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
6
|
|
Overall Study
Lost to Follow-up
|
11
|
17
|
|
Overall Study
Protocol Violation
|
8
|
23
|
|
Overall Study
Withdrawal by Subject
|
7
|
17
|
|
Overall Study
MOVING OUT OF STATE
|
1
|
0
|
|
Overall Study
Pregnancy
|
3
|
3
|
|
Overall Study
SPONSOR STOPPED STUDY
|
2
|
2
|
|
Overall Study
SPONSOR REQUEST
|
0
|
1
|
|
Overall Study
Lost to Follow up but returned per GSK
|
0
|
1
|
|
Overall Study
Closed per sponsor
|
0
|
1
|
Baseline Characteristics
A Study Comparing Daily Treatment With Valaciclovir To Placebo For Suppression Of Herpes Simplex Virus HSV-2 Genital Herpes In Newly Diagnosed Patients. VALTREX® Tablet is a Trademark of the GlaxoSmithKline Group of Companies.
Baseline characteristics by cohort
| Measure |
Placebo
n=128 Participants
Participants randomized to this treatment arm received matching placebo to valacyclovir 1 g given as 2 x 500 mg caplets QD for 6 months (24 weeks). Participants with GH recurrences during the study temporarily discontinued their blinded treatment assignment and received open label valaciclovir 500 mg BID for 3 days after which the double-blind therapy was resumed.
|
Valaciclovir 1g QD
n=255 Participants
Participants received double blinded treatment of oral dose of valacyclovir 1 g given as 2 x 500 mg caplets QD for 6 months (24 weeks). Participants with GH recurrences during the study temporarily discontinued their blinded treatment assignment and received open label valaciclovir 500mg BID for 3 days after which the double-blind therapy was resumed.
|
Total
n=383 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
32.2 Years
STANDARD_DEVIATION 11.52 • n=5 Participants
|
30.9 Years
STANDARD_DEVIATION 10.48 • n=7 Participants
|
31.3 Years
STANDARD_DEVIATION 10.84 • n=5 Participants
|
|
Sex: Female, Male
Female
|
92 Participants
n=5 Participants
|
176 Participants
n=7 Participants
|
268 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
36 Participants
n=5 Participants
|
79 Participants
n=7 Participants
|
115 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · American Hispanic
|
17 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Arabic/North African
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Black
|
39 Participants
n=5 Participants
|
84 Participants
n=7 Participants
|
123 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · East & South East Asian
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · White/Caucasian
|
68 Participants
n=5 Participants
|
125 Participants
n=7 Participants
|
193 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Unknown
|
4 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 168Population: ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product.
Diary cards were issued to the participants during randomization visit for recording GH recurrences. HSV recurrences since the last visit was assessed after review of the diary card and discussion with the participant. The percentage of participants with time to first GH recurrence was based on Kaplan-Meier estimates. Confidence intervals for differences in proportions was calculated using the standard error for the Kaplan-Meier estimate derived using Greenwood's formula.
Outcome measures
| Measure |
Placebo
n=128 Participants
Participants received double blinded treatment of oral dose of matching placebo to Valacyclovir 1 g given as 2 x 500 mg caplets QD for 6 months (24 weeks). Participants with GH recurrences during the study temporarily discontinued their blinded treatment assignment and received open label valaciclovir 500 mg BID for 3 days after which the double-blind therapy was resumed.
|
Valaciclovir 1g QD
n=255 Participants
Participants received double blinded treatment of oral dose of Valacyclovir 1 g given as 2 x 500 mg caplets QD for 6 months (24 weeks). Participants with GH recurrences during the study temporarily discontinued their blinded treatment assignment and received open label valaciclovir 500 mg BID for 3 days after which the double-blind therapy was resumed.
|
|---|---|---|
|
Percentage of Participants With Time to First GH Recurrence
|
43 Percentage of participants
|
71 Percentage of participants
|
SECONDARY outcome
Timeframe: Up to Day 168Population: ITT population. Only those participants available at the specified time points were analyzed.
Mean number of GH recurrence reaching macular/papular stage per month was reported. Diary cards were issued to the participants during randomization visit for the recording GH recurrences. HSV recurrences since the last visit was assessed after review of the diary card and discussion with the participant.
Outcome measures
| Measure |
Placebo
n=122 Participants
Participants received double blinded treatment of oral dose of matching placebo to Valacyclovir 1 g given as 2 x 500 mg caplets QD for 6 months (24 weeks). Participants with GH recurrences during the study temporarily discontinued their blinded treatment assignment and received open label valaciclovir 500 mg BID for 3 days after which the double-blind therapy was resumed.
|
Valaciclovir 1g QD
n=227 Participants
Participants received double blinded treatment of oral dose of Valacyclovir 1 g given as 2 x 500 mg caplets QD for 6 months (24 weeks). Participants with GH recurrences during the study temporarily discontinued their blinded treatment assignment and received open label valaciclovir 500 mg BID for 3 days after which the double-blind therapy was resumed.
|
|---|---|---|
|
Mean Number of GH Recurrences Per Month Within the 6-month Study Period
|
0.48 Number of recurrences
Standard Deviation 1.860
|
0.11 Number of recurrences
Standard Deviation 0.254
|
SECONDARY outcome
Timeframe: Upto Day 168Population: ITT population
An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE was defined as any untoward medical occurrence that, at any dose results in death, was life-threatening, required hospitalization or prolongation of hospitalization, results in disability/incapacity, was a congenital anomaly/birth defect or medically significant.
Outcome measures
| Measure |
Placebo
n=128 Participants
Participants received double blinded treatment of oral dose of matching placebo to Valacyclovir 1 g given as 2 x 500 mg caplets QD for 6 months (24 weeks). Participants with GH recurrences during the study temporarily discontinued their blinded treatment assignment and received open label valaciclovir 500 mg BID for 3 days after which the double-blind therapy was resumed.
|
Valaciclovir 1g QD
n=255 Participants
Participants received double blinded treatment of oral dose of Valacyclovir 1 g given as 2 x 500 mg caplets QD for 6 months (24 weeks). Participants with GH recurrences during the study temporarily discontinued their blinded treatment assignment and received open label valaciclovir 500 mg BID for 3 days after which the double-blind therapy was resumed.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Any AEs
|
98 Participants
|
185 Participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Any SAEs
|
4 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Day 168Population: ITT population
Diary cards were issued to the participants during randomization visit for recording HSV outbreak within 6-momths. HSV outbreak was assessed after review of the diary card and discussion with the participant. The percentage of participants who had first oral HSV outbreak at 6-months was reported.
Outcome measures
| Measure |
Placebo
n=128 Participants
Participants received double blinded treatment of oral dose of matching placebo to Valacyclovir 1 g given as 2 x 500 mg caplets QD for 6 months (24 weeks). Participants with GH recurrences during the study temporarily discontinued their blinded treatment assignment and received open label valaciclovir 500 mg BID for 3 days after which the double-blind therapy was resumed.
|
Valaciclovir 1g QD
n=255 Participants
Participants received double blinded treatment of oral dose of Valacyclovir 1 g given as 2 x 500 mg caplets QD for 6 months (24 weeks). Participants with GH recurrences during the study temporarily discontinued their blinded treatment assignment and received open label valaciclovir 500 mg BID for 3 days after which the double-blind therapy was resumed.
|
|---|---|---|
|
Percentage of Participants With Time to First Oral Herpes Simplex Virus (HSV) Outbreak Within 6-months
|
11 Percentage of participants
|
14 Percentage of participants
|
SECONDARY outcome
Timeframe: Day 168Population: ITT population.
Culture samples were tested for AVC-susceptibility by the analytical laboratory. Re-testing of the ACV resistant isolates was carried out to check if the half maximal inhibitory concentration (IC-50s) for all the ACV resistant isolates were within the expected errors of 2.0 microgram per milliliters (mcg/ml) cut-off for the plaque reduction assay. Those isolates that confirm to be resistant in repeat assays were considered as resistant to ACV.
Outcome measures
| Measure |
Placebo
n=128 Participants
Participants received double blinded treatment of oral dose of matching placebo to Valacyclovir 1 g given as 2 x 500 mg caplets QD for 6 months (24 weeks). Participants with GH recurrences during the study temporarily discontinued their blinded treatment assignment and received open label valaciclovir 500 mg BID for 3 days after which the double-blind therapy was resumed.
|
Valaciclovir 1g QD
n=255 Participants
Participants received double blinded treatment of oral dose of Valacyclovir 1 g given as 2 x 500 mg caplets QD for 6 months (24 weeks). Participants with GH recurrences during the study temporarily discontinued their blinded treatment assignment and received open label valaciclovir 500 mg BID for 3 days after which the double-blind therapy was resumed.
|
|---|---|---|
|
Number of Isolates With Resistance to Acyclovir (ACV)
|
0 Number of isolates
|
0 Number of isolates
|
Adverse Events
Placebo
Serious events: 4 serious events
Other events: 75 other events
Deaths: 0 deaths
Valaciclovir 1g QD
Serious events: 3 serious events
Other events: 138 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Placebo
n=128 participants at risk
Participants received double blinded treatment of oral dose of matching placebo to Valacyclovir 1 g given as 2 x 500 mg caplets QD for 6 months (24 weeks). Participants with GH recurrences during the study temporarily discontinued their blinded treatment assignment and received open label valaciclovir 500 mg BID for 3 days after which the double-blind therapy was resumed.
|
Valaciclovir 1g QD
n=255 participants at risk
Participants received double blinded treatment of oral dose of Valacyclovir 1 g given as 2 x 500 mg caplets QD for 6 months (24 weeks). Participants with GH recurrences during the study temporarily discontinued their blinded treatment assignment and received open label valaciclovir 500 mg BID for 3 days after which the double-blind therapy was resumed.
|
|---|---|---|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
1.6%
2/128 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
0.39%
1/255 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
|
Infections and infestations
Appendicitis
|
0.00%
0/128 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
0.39%
1/255 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
|
Injury, poisoning and procedural complications
Gun shot wound
|
0.00%
0/128 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
0.39%
1/255 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.78%
1/128 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
0.00%
0/255 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphoma
|
0.78%
1/128 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
0.00%
0/255 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
Other adverse events
| Measure |
Placebo
n=128 participants at risk
Participants received double blinded treatment of oral dose of matching placebo to Valacyclovir 1 g given as 2 x 500 mg caplets QD for 6 months (24 weeks). Participants with GH recurrences during the study temporarily discontinued their blinded treatment assignment and received open label valaciclovir 500 mg BID for 3 days after which the double-blind therapy was resumed.
|
Valaciclovir 1g QD
n=255 participants at risk
Participants received double blinded treatment of oral dose of Valacyclovir 1 g given as 2 x 500 mg caplets QD for 6 months (24 weeks). Participants with GH recurrences during the study temporarily discontinued their blinded treatment assignment and received open label valaciclovir 500 mg BID for 3 days after which the double-blind therapy was resumed.
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
10.2%
13/128 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
13.7%
35/255 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
|
Infections and infestations
Herpes simplex
|
6.2%
8/128 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
8.6%
22/255 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
|
Infections and infestations
Vulvovaginal mycotic infection
|
9.4%
12/128 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
6.3%
16/255 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
|
Infections and infestations
Urinary tract infection
|
7.0%
9/128 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
2.7%
7/255 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
|
Infections and infestations
Influenza
|
5.5%
7/128 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
2.7%
7/255 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
|
Nervous system disorders
Headache
|
30.5%
39/128 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
23.1%
59/255 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
8.6%
11/128 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
6.3%
16/255 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
|
Gastrointestinal disorders
Nausea
|
7.8%
10/128 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
4.3%
11/255 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
4.7%
6/128 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
5.1%
13/255 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
3.1%
4/128 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
5.5%
14/255 • AEs were collected up to end of study (Day 168).
ITT population was defined as all participants randomized to treatment who were administered at least one dose of investigational product. ITT population was used for reporting adverse event.
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER