Trial Outcomes & Findings for Efficacy and Safety of Famciclovir 1-day Treatment Compared to 3-day Treatment With Valacyclovir in Adults With Recurrent Genital Herpes (NCT NCT00306787)

NCT ID: NCT00306787

Last Updated: 2011-06-30

Results Overview

Time to healing of all non-aborted genital herpes lesions was defined as the time from the first dose of study drug taken no earlier than the recurrence of genital herpes to the investigator-assessed time of healing (i.e. loss of all crusts and re-epithelialization of the lesions; erythema could have been present). Non-aborted lesions are lesions which underwent vesicle, ulcer/soft crust, and/or hard crust formation and required re-epithelialization for healing. The median time was estimated using Kaplan-Meier method by censoring missing values at the time of last clinical lesion observation.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1179 participants
• Primary outcome timeframe: 72 hours after initiation of study medication up to Day 20
• Results posted on: 2011-06-30

Participant Flow

A total of 1179 patients were randomized in the study and followed to their first genital herpes recurrence. A total of 423 patients did not experience a recurrence within 4 months of randomization therefore, no treatment was initiated and study drug was not taken. A total of 756 patients were randomized and took study drug (safety population).

Participant milestones

Measure	Famciclovir Patients received Famciclovir 1000 mg (2 x 500 mg tablets) twice a day for one day. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions and the second dose approximately 12 hours later. Patients also received 1 valacyclovir placebo capsule, beginning with the first famciclovir dose, twice a day for 3 days, each taken about 12 hours apart.	Valacyclovir Patients received Valacyclovir 500 mg capsule twice a day (b.i.d) approximately 12 hours apart for 3 consecutive days. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions. On the first day patients also received 2 famciclovir placebo tablets taken with the first 2 doses of Valacyclovir.
Overall Study STARTED	579	600
Overall Study Received Study Drug (Safety Population)	371	385
Overall Study Intent to Treat (ITT) Population	370	381
Overall Study COMPLETED	345	359
Overall Study NOT COMPLETED	234	241

Reasons for withdrawal

Measure	Famciclovir Patients received Famciclovir 1000 mg (2 x 500 mg tablets) twice a day for one day. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions and the second dose approximately 12 hours later. Patients also received 1 valacyclovir placebo capsule, beginning with the first famciclovir dose, twice a day for 3 days, each taken about 12 hours apart.	Valacyclovir Patients received Valacyclovir 500 mg capsule twice a day (b.i.d) approximately 12 hours apart for 3 consecutive days. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions. On the first day patients also received 2 famciclovir placebo tablets taken with the first 2 doses of Valacyclovir.
Overall Study Discontinued without taking study drug	208	215
Overall Study Adverse Event	1	1
Overall Study Lack of Efficacy	1	0
Overall Study Protocol Violation	8	10
Overall Study Withdrawal by Subject	2	9
Overall Study Lost to Follow-up	9	6
Overall Study Administrative problems	4	0
Overall Study Abnormal laboratory value(s)	1	0

Baseline Characteristics

Efficacy and Safety of Famciclovir 1-day Treatment Compared to 3-day Treatment With Valacyclovir in Adults With Recurrent Genital Herpes

Baseline characteristics by cohort

Measure	Famciclovir n=370 Participants Patients received Famciclovir 1000 mg (2 x 500 mg tablets) twice a day for one day. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions and the second dose approximately 12 hours later. Patients also received 1 valacyclovir placebo capsule, beginning with the first famciclovir dose, twice a day for 3 days, each taken about 12 hours apart.	Valacyclovir n=381 Participants Patients received Valacyclovir 500 mg capsule twice a day (b.i.d) approximately 12 hours apart for 3 consecutive days. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions. On the first day patients also received 2 famciclovir placebo tablets taken with the first 2 doses of Valacyclovir.	Total n=751 Participants Total of all reporting groups
Age Continuous	39.6 years STANDARD_DEVIATION 11.6 • n=5 Participants	41.7 years STANDARD_DEVIATION 12.6 • n=7 Participants	40.7 years STANDARD_DEVIATION 12.2 • n=5 Participants
Sex: Female, Male Female	245 Participants n=5 Participants	243 Participants n=7 Participants	488 Participants n=5 Participants
Sex: Female, Male Male	125 Participants n=5 Participants	138 Participants n=7 Participants	263 Participants n=5 Participants

PRIMARY outcome

Timeframe: 72 hours after initiation of study medication up to Day 20

Population: Modified Intent To Treat (mITT) population. The mITT population included all patients who initiated treatment with the study drug, with the intention of treating genital herpes recurrences who developed non-aborted genital herpes lesions during the treated recurrence except those with confirmed aborted lesions at the final clinical assessment.

Time to healing of all non-aborted genital herpes lesions was defined as the time from the first dose of study drug taken no earlier than the recurrence of genital herpes to the investigator-assessed time of healing (i.e. loss of all crusts and re-epithelialization of the lesions; erythema could have been present). Non-aborted lesions are lesions which underwent vesicle, ulcer/soft crust, and/or hard crust formation and required re-epithelialization for healing. The median time was estimated using Kaplan-Meier method by censoring missing values at the time of last clinical lesion observation.

Outcome measures

Measure	Famciclovir n=249 Participants Patients received Famciclovir 1000 mg (2 x 500 mg tablets) twice a day for one day. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions and the second dose approximately 12 hours later. Patients also received 1 valacyclovir placebo capsule, beginning with the first famciclovir dose, twice a day for 3 days, each taken about 12 hours apart.	Valacyclovir n=253 Participants Patients received Valacyclovir 500 mg capsule twice a day (b.i.d) approximately 12 hours apart for 3 consecutive days. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions. On the first day patients also received 2 famciclovir placebo tablets taken with the first 2 doses of Valacyclovir.
Investigator-assessed Time to Healing of All Non-aborted Genital Herpes Lesions	4.25 days Interval 3.06 to 5.78	4.08 days Interval 3.02 to 5.8

SECONDARY outcome

Timeframe: 72 hours after initiation of study medication up to Day 20

Population: ITT population. Patients who discontinued from the study before healing of non-aborted lesions was confirmed and patients who completed the study after 21 days since treatment initiation without non-aborted lesion stages and without a final assessment on aborted lesion status were assumed to have non-aborted lesions in this analysis.

Lesions that developed no further than the papule stage (erythema may have been present) were considered as aborted lesions. Prodrome also was considered the sign of aborted lesions in this study. Lesions which underwent vesicle, ulcer/soft crust, and/or hard crust formation and required re-epithelialization for healing were considered as non-aborted lesions.

Outcome measures

Measure	Famciclovir n=370 Participants Patients received Famciclovir 1000 mg (2 x 500 mg tablets) twice a day for one day. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions and the second dose approximately 12 hours later. Patients also received 1 valacyclovir placebo capsule, beginning with the first famciclovir dose, twice a day for 3 days, each taken about 12 hours apart.	Valacyclovir n=381 Participants Patients received Valacyclovir 500 mg capsule twice a day (b.i.d) approximately 12 hours apart for 3 consecutive days. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions. On the first day patients also received 2 famciclovir placebo tablets taken with the first 2 doses of Valacyclovir.
Percentage of Participants With Aborted Genital Herpes Lesions Aborted Lesions	32.7 Percentage of participants	33.6 Percentage of participants
Percentage of Participants With Aborted Genital Herpes Lesions Non-Aborted lesions	67.3 Percentage of participants	66.4 Percentage of participants

SECONDARY outcome

Timeframe: 72 hours after initiation of study medication up to Day 20

Population: ITT population. Median time was estimated by kaplan-Meier method by censoring the missing non-aborted times at last clinical observation. Patients with aborted lesions were assigned a time to healing of zero.

Lesions that developed no further than the papule stage (erythema may have been present) were considered as aborted lesions. Prodrome also was considered the sign of aborted lesions in this study. Lesions which underwent vesicle, ulcer/soft crust, and/or hard crust formation and required re-epithelialization for healing were considered as non-aborted lesions. The median time was estimated using Kaplan-Meier method.

Outcome measures

Measure	Famciclovir n=370 Participants Patients received Famciclovir 1000 mg (2 x 500 mg tablets) twice a day for one day. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions and the second dose approximately 12 hours later. Patients also received 1 valacyclovir placebo capsule, beginning with the first famciclovir dose, twice a day for 3 days, each taken about 12 hours apart.	Valacyclovir n=381 Participants Patients received Valacyclovir 500 mg capsule twice a day (b.i.d) approximately 12 hours apart for 3 consecutive days. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions. On the first day patients also received 2 famciclovir placebo tablets taken with the first 2 doses of Valacyclovir.
Investigator-assessed Time to Healing of All (Non-aborted and Aborted) Genital Herpes Lesions	3.07 days Interval 0.0 to 5.0	3.01 days Interval 0.0 to 4.88

SECONDARY outcome

Timeframe: 72 hours after initiation of study medication up to Day 20

Population: ITT population. If the resolution of any or all symptoms was not confirmed by a subsequent visit or diary entry, the time to resolution was censored at the time of the last diary entry. If a patient dropped out before any diary entries were created, the patient was assigned a censoring time of 0. n= number of patients with symptoms.

Kaplan-Meier estimated time in hours of the resolution of all symptoms (pain, burning, itching, tingling and tenderness) associated with recurrent genital herpes. Kaplan-Meier method is used to estimate the time to resolution of symptoms.

Outcome measures

Measure	Famciclovir n=370 Participants Patients received Famciclovir 1000 mg (2 x 500 mg tablets) twice a day for one day. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions and the second dose approximately 12 hours later. Patients also received 1 valacyclovir placebo capsule, beginning with the first famciclovir dose, twice a day for 3 days, each taken about 12 hours apart.	Valacyclovir n=381 Participants Patients received Valacyclovir 500 mg capsule twice a day (b.i.d) approximately 12 hours apart for 3 consecutive days. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions. On the first day patients also received 2 famciclovir placebo tablets taken with the first 2 doses of Valacyclovir.
Time to Resolution of Symptoms Associated With Recurrent Genital Herpes Tingling (n = 266, 275)	23.8 hours Interval 0.0 to 58.0	23.0 hours Interval 0.0 to 50.5
Time to Resolution of Symptoms Associated With Recurrent Genital Herpes Pain (n = 220, 228)	18.0 hours Interval 0.0 to 52.7	20.3 hours Interval 0.0 to 46.6
Time to Resolution of Symptoms Associated With Recurrent Genital Herpes Burning (n = 221, 218)	16.1 hours Interval 0.0 to 50.5	12.6 hours Interval 0.0 to 47.5
Time to Resolution of Symptoms Associated With Recurrent Genital Herpes Itching (n = 309, 297)	43.9 hours Interval 12.2 to 76.7	43.5 hours Interval 11.5 to 85.6
Time to Resolution of Symptoms Associated With Recurrent Genital Herpes Tenderness (n = 298, 311)	55.2 hours Interval 20.4 to 106.0	48.0 hours Interval 14.3 to 87.3

SECONDARY outcome

Timeframe: Up to 6 months after investigator assessed healing of first recurrence of genital herpes

Population: ITT population included all randomized patients who initiated treatment with (i.e. received any dose of) the study drug, with the intention of treating genital herpes recurrences.

Patients who experienced a first recurrence of genital herpes and took study medication were followed for a period of up to 6 months to the second recurrence.

Outcome measures

Measure	Famciclovir n=370 Participants Patients received Famciclovir 1000 mg (2 x 500 mg tablets) twice a day for one day. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions and the second dose approximately 12 hours later. Patients also received 1 valacyclovir placebo capsule, beginning with the first famciclovir dose, twice a day for 3 days, each taken about 12 hours apart.	Valacyclovir n=381 Participants Patients received Valacyclovir 500 mg capsule twice a day (b.i.d) approximately 12 hours apart for 3 consecutive days. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions. On the first day patients also received 2 famciclovir placebo tablets taken with the first 2 doses of Valacyclovir.
Number of Patients With a Second Recurrence of Genital Herpes Patients continued in follow up period	324 participants	342 participants
Number of Patients With a Second Recurrence of Genital Herpes Patients with 2nd recurrence in follow up period	226 participants	231 participants

SECONDARY outcome

Timeframe: Up to 6 months after investigator assessed healing of first recurrence of genital herpes

Population: ITT population. Patients with missing time-to-second recurrence were not included in the calculation of the median.

Patients who experienced a first recurrence of genital herpes and took study medication were followed for a period of up to 6 months to the second recurrence. Time to a second recurrence of genital herpes was calculated in 2 ways as follows:

1. From the date of treatment initiation no earlier than the recurrence of genital herpes to the date of onset for the second recurrence, or

2. From the date of healing of non-aborted lesions or confirmation of aborted lesions to the date of onset for the second recurrence.

Outcome measures

Measure	Famciclovir n=226 Participants Patients received Famciclovir 1000 mg (2 x 500 mg tablets) twice a day for one day. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions and the second dose approximately 12 hours later. Patients also received 1 valacyclovir placebo capsule, beginning with the first famciclovir dose, twice a day for 3 days, each taken about 12 hours apart.	Valacyclovir n=231 Participants Patients received Valacyclovir 500 mg capsule twice a day (b.i.d) approximately 12 hours apart for 3 consecutive days. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions. On the first day patients also received 2 famciclovir placebo tablets taken with the first 2 doses of Valacyclovir.
Time to a Second Recurrence of Genital Herpes From treatment initiation	33.5 days Interval 18.0 to 67.0	38.0 days Interval 18.0 to 73.0
Time to a Second Recurrence of Genital Herpes From date of healing /confirmation	27.5 days Interval 14.0 to 63.0	32.0 days Interval 14.0 to 69.0

Adverse Events

Famciclovir

Serious events: 2 serious events

Other events: 66 other events

Deaths: 0 deaths

Valacyclovir

Serious events: 1 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Measure	Famciclovir n=371 participants at risk Patients received Famciclovir 1000 mg (2 x 500 mg tablets) twice a day for one day. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions and the second dose approximately 12 hours later. Patients also received 1 valacyclovir placebo capsule, beginning with the first famciclovir dose, twice a day for 3 days, each taken about 12 hours apart.	Valacyclovir n=385 participants at risk Patients received Valacyclovir 500 mg capsule twice a day (b.i.d) approximately 12 hours apart for 3 consecutive days. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions. On the first day patients also received 2 famciclovir placebo tablets taken with the first 2 doses of Valacyclovir.
Cardiac disorders Myocardial ischemia	0.27% 1/371 • 30 days post last dose of study medication Safety Population	0.00% 0/385 • 30 days post last dose of study medication Safety Population
Psychiatric disorders Suicide Attempt	0.27% 1/371 • 30 days post last dose of study medication Safety Population	0.00% 0/385 • 30 days post last dose of study medication Safety Population
Psychiatric disorders Substance Abuse	0.00% 0/371 • 30 days post last dose of study medication Safety Population	0.26% 1/385 • 30 days post last dose of study medication Safety Population

Other adverse events

Measure	Famciclovir n=371 participants at risk Patients received Famciclovir 1000 mg (2 x 500 mg tablets) twice a day for one day. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions and the second dose approximately 12 hours later. Patients also received 1 valacyclovir placebo capsule, beginning with the first famciclovir dose, twice a day for 3 days, each taken about 12 hours apart.	Valacyclovir n=385 participants at risk Patients received Valacyclovir 500 mg capsule twice a day (b.i.d) approximately 12 hours apart for 3 consecutive days. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions. On the first day patients also received 2 famciclovir placebo tablets taken with the first 2 doses of Valacyclovir.
Nervous system disorders Headache	7.8% 29/371 • 30 days post last dose of study medication Safety Population	4.4% 17/385 • 30 days post last dose of study medication Safety Population
Gastrointestinal disorders Nausea	6.2% 23/371 • 30 days post last dose of study medication Safety Population	4.7% 18/385 • 30 days post last dose of study medication Safety Population
Gastrointestinal disorders Diarrhea	2.2% 8/371 • 30 days post last dose of study medication Safety Population	1.3% 5/385 • 30 days post last dose of study medication Safety Population
Gastrointestinal disorders Vomiting	1.3% 5/371 • 30 days post last dose of study medication Safety Population	0.78% 3/385 • 30 days post last dose of study medication Safety Population
Gastrointestinal disorders Abdominal pain	0.27% 1/371 • 30 days post last dose of study medication Safety Population	1.0% 4/385 • 30 days post last dose of study medication Safety Population

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER