Trial Outcomes & Findings for Patient-initiated Episodic Treatment of Recurrent Genital Herpes in Black Patients (NCT NCT00477334)

Last Updated: 2011-03-28

Results Overview

Time to healing of all non-aborted genital herpes lesions, defined as the time from the first dose of study medication to the investigator-assessed time of healing (i.e. loss of all crusts and re-epithelialization of lesions; erythema may be present).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

463 participants

Primary outcome timeframe

21 days

Results posted on

2011-03-28

Participant Flow

Participant milestones

Participant milestones
Measure	Famciclovir 1000 mg Famciclovir 1000 mg; twice a day for one day for treatment.	Placebo Comparator Placebo twice a day for one day for treatment.
Overall Study STARTED	312	151
Overall Study Randomized and Took Study Drug	206	98
Overall Study Intent to Treat Population	201	98
Overall Study Participants Completing First Recurrence	187	92
Overall Study Modified Intent to Treat Population	152	78
Overall Study COMPLETED	142	75
Overall Study NOT COMPLETED	170	76

Reasons for withdrawal

Reasons for withdrawal
Measure	Famciclovir 1000 mg Famciclovir 1000 mg; twice a day for one day for treatment.	Placebo Comparator Placebo twice a day for one day for treatment.
Overall Study Discontinued prior to taking study drug	106	53
Overall Study Adverse Event	1	2
Overall Study Withdrawal by Subject	2	1
Overall Study Lost to Follow-up	15	4
Overall Study Administrative Problems	39	15
Overall Study Protocol Violation	7	1

Baseline Characteristics

Patient-initiated Episodic Treatment of Recurrent Genital Herpes in Black Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Famciclovir 1000 mg n=201 Participants Famciclovir 1000 mg; twice a day for one day for treatment.	Placebo Comparator n=98 Participants Placebo twice a day for one day for treatment.	Total n=299 Participants Total of all reporting groups
Age Continuous	37.5 years STANDARD_DEVIATION 10.35 • n=5 Participants	38.5 years STANDARD_DEVIATION 10.34 • n=7 Participants	37.8 years STANDARD_DEVIATION 10.34 • n=5 Participants
Sex: Female, Male Female	127 Participants n=5 Participants	69 Participants n=7 Participants	196 Participants n=5 Participants
Sex: Female, Male Male	74 Participants n=5 Participants	29 Participants n=7 Participants	103 Participants n=5 Participants
Number of Years: recurrent genital herpes	6.9 Years STANDARD_DEVIATION 6.75 • n=5 Participants	7.0 Years STANDARD_DEVIATION 6.50 • n=7 Participants	7.0 Years STANDARD_DEVIATION 6.66 • n=5 Participants
Genital herpes recurrence in last 12 months	6.0 Genital herpes recurrences STANDARD_DEVIATION 3.26 • n=5 Participants	5.8 Genital herpes recurrences STANDARD_DEVIATION 2.72 • n=7 Participants	5.9 Genital herpes recurrences STANDARD_DEVIATION 3.09 • n=5 Participants

PRIMARY outcome

Timeframe: 21 days

Population: Modified Intent to Treat Population (mITT) that includes all Intent to Treat participants with non-aborted genital herpes lesions during the treatment period.

Outcome measures

Outcome measures
Measure	Famciclovir 1000 mg n=152 Participants Famciclovir 1000 mg; twice a day for one day for treatment.	Placebo Comparator n=78 Participants Placebo twice a day for one day for treatment.	Grade 3 Toxicity	Grade 4 Toxicity
Investigator Assessed Time to Healing of All Non-aborted Genital Herpes Lesions	5.38 Days Interval 3.82 to 7.35	4.79 Days Interval 3.56 to 7.03	—	—

SECONDARY outcome

Timeframe: 21 days

Population: Intent-to-Treat (ITT). All randomized participants who initiated treatment (i.e. received any dose of the study drug) with the intention of treating genital herpes recurrences.

Outcome measures

Outcome measures
Measure	Famciclovir 1000 mg n=201 Participants Famciclovir 1000 mg; twice a day for one day for treatment.	Placebo Comparator n=98 Participants Placebo twice a day for one day for treatment.	Grade 3 Toxicity	Grade 4 Toxicity
Percentage of Participants With Aborted and Non-aborted Genital Herpes Lesions During the Treatment Period Percentage with aborted lesions (n=49,20)	24.4 Percentage of Participants	20.4 Percentage of Participants	—	—
Percentage of Participants With Aborted and Non-aborted Genital Herpes Lesions During the Treatment Period Percentage with non-aborted lesions (n= 152,78)	75.6 Percentage of Participants	79.6 Percentage of Participants	—	—

SECONDARY outcome

Timeframe: 21 days

Population: ITT participants who discontinued from the study before healing of non aborted lesions was confirmed and participants 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 as having non aborted lesions in this analysis.

Kaplan-Meier estimation.

Outcome measures

Outcome measures
Measure	Famciclovir 1000 mg n=201 Participants Famciclovir 1000 mg; twice a day for one day for treatment.	Placebo Comparator n=98 Participants Placebo twice a day for one day for treatment.	Grade 3 Toxicity	Grade 4 Toxicity
Investigator Assessed Time to Healing of All Non-aborted and Aborted Genital Herpes Lesions	4.13 Days Interval 1.24 to 6.0	4.06 Days Interval 2.01 to 6.64	—	—

SECONDARY outcome

Timeframe: 72 hour after initiation of study medication up to 21 days

Population: Intent to Treat Population. If a participant never had a symptom prior to the last valid diary entry for the first recurrence, then the time to resolution of the symptom was set to missing and the participant was not included in the analysis.

Median time to resolution of symptoms: all symptoms, pain, burning, itching, tingling and tenderness associated with recurrent genital herpes estimated using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Famciclovir 1000 mg n=201 Participants Famciclovir 1000 mg; twice a day for one day for treatment.	Placebo Comparator n=98 Participants Placebo twice a day for one day for treatment.	Grade 3 Toxicity	Grade 4 Toxicity
Time to Resolution of Symptoms Associated With Recurrent Genital Herpes Burning (n=126,65)	2.3 Days Interval 1.0 to 4.0	2.5 Days Interval 1.5 to 4.4	—	—
Time to Resolution of Symptoms Associated With Recurrent Genital Herpes All symptoms (n=195/98)	4.5 Days Interval 2.8 to 8.2	5.7 Days Interval 2.8 to 9.0	—	—
Time to Resolution of Symptoms Associated With Recurrent Genital Herpes Pain (n=141,69)	3.0 Days Interval 1.5 to 5.3	2.6 Days Interval 1.5 to 5.9	—	—
Time to Resolution of Symptoms Associated With Recurrent Genital Herpes Itching (n=168,86)	3.2 Days Interval 1.5 to 6.0	3.5 Days Interval 1.6 to 6.6	—	—
Time to Resolution of Symptoms Associated With Recurrent Genital Herpes Tingling (n=141,70)	2.0 Days Interval 1.0 to 4.2	2.3 Days Interval 1.1 to 5.9	—	—
Time to Resolution of Symptoms Associated With Recurrent Genital Herpes Tenderness (n=147/74)	3.4 Days Interval 1.6 to 6.5	2.9 Days Interval 1.6 to 6.0	—	—

SECONDARY outcome

Timeframe: 6 months

Population: Intent to Treat Population: participants who completed the first recurrence.

Number of participants with a second recurrence of genital herpes in the follow-up period.

Outcome measures

Outcome measures
Measure	Famciclovir 1000 mg n=185 Participants Famciclovir 1000 mg; twice a day for one day for treatment.	Placebo Comparator n=92 Participants Placebo twice a day for one day for treatment.	Grade 3 Toxicity	Grade 4 Toxicity
Number of Participants With a Second Recurrence of Genital Herpes in the Follow-up Period	141 Participants	75 Participants	—	—

SECONDARY outcome

Timeframe: 6 months

Population: Intent to Treat Population: participants who completed the first recurrence.

Kaplan Meier estimated time in days to second recurrent from treatment initiation and from the date of healing of aborted lesions.

Outcome measures

Outcome measures
Measure	Famciclovir 1000 mg n=185 Participants Famciclovir 1000 mg; twice a day for one day for treatment.	Placebo Comparator n=92 Participants Placebo twice a day for one day for treatment.	Grade 3 Toxicity	Grade 4 Toxicity
Time to Second Recurrence of Genital Herpes Time from initiation of treatment	69.0 Days Interval 31.0 to 143.0	81.0 Days Interval 31.0 to 122.0	—	—
Time to Second Recurrence of Genital Herpes Time from healing of non-aborted lesion	63.0 Days Interval 25.0 to 137.0	75.0 Days Interval 24.0 to 118.0	—	—

SECONDARY outcome

Timeframe: Baseline, Day 2

Population: 304 Participants = 206 participants in the Famciclovir Group + 98 participants in the Placebo Group. Individual n values in each of the categories is the number of participants in the group with normal baseline values and at least one non-missing post baseline measurement.

The number of participants with clinically noted shifts in Hematology tests from normal at baseline are graded based on Division of Microbiology and Infectious Diseases (DMID) toxicity tables from Grade 1 toxicity (smallest change) to Grade 4 toxicity (largest change). Grade 3 and 4 toxicities are considered to be clinically meaningful.

Outcome measures

Outcome measures
Measure	Famciclovir 1000 mg n=304 Participants Famciclovir 1000 mg; twice a day for one day for treatment.	Placebo Comparator n=304 Participants Placebo twice a day for one day for treatment.	Grade 3 Toxicity n=304 Participants	Grade 4 Toxicity n=304 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Hematology Test and Treatment Haematocrit-Famciclovir (n=186)	0 Participants	0 Participants	0 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Hematology Test and Treatment Haemoglobin-Famciclovir (n=183)	2 Participants	0 Participants	0 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Hematology Test and Treatment Absolute Neutrophils-Famciclovir (n=177)	6 Participants	2 Participants	0 Participants	1 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Hematology Test and Treatment Platelet count-Famciclovir (n=184)	0 Participants	0 Participants	0 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Hematology Test and Treatment Platelet count-Placebo (n=88)	0 Participants	0 Participants	1 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Hematology Test and Treatment Haematocrit-Placebo (n=87)	0 Participants	0 Participants	0 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Hematology Test and Treatment Haemoglobin-Placebo(n=88)	3 Participants	0 Participants	0 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Hematology Test and Treatment Absolute Neutrophils-Placebo (n=83)	0 Participants	0 Participants	1 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Hematology Test and Treatment WBC(total)-Famciclovir (n=163)	15 Participants	1 Participants	0 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Hematology Test and Treatment WBC(total)-Placebo(n=98)	6 Participants	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Day 2

The number of participants with clinically noted shifts in Clinical Chemistry tests from normal at baseline are graded based on Division of Microbiology and Infectious Diseases (DMID) toxicity tables from Grade 1 toxicity (smallest change) to Grade 4 toxicity (largest change). Grade 3 and 4 toxicities are considered to be clinically meaningful. SGPT(ALT)= Serum Glutamic Pyruvate Transaminase (Alanine Aminotransferase) and SGOT(AST)= Serum Glutamic Oxalacetic Transaminase (Aspartate Aminotransferase)

Outcome measures

Outcome measures
Measure	Famciclovir 1000 mg n=304 Participants Famciclovir 1000 mg; twice a day for one day for treatment.	Placebo Comparator n=304 Participants Placebo twice a day for one day for treatment.	Grade 3 Toxicity n=304 Participants	Grade 4 Toxicity n=304 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Chemistry Test and Treatment Blood Urea Nitrogen-Placebo (n=95)	0 Participants	0 Participants	0 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Chemistry Test and Treatment Creatinine-Famciclovir (n=182)	16 Participants	0 Participants	0 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Chemistry Test and Treatment Lipase-Placebo (n=90)	1 Participants	1 Participants	0 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Chemistry Test and Treatment SGPT(ALT)-Famciclovir (n=183)	3 Participants	0 Participants	0 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Chemistry Test and Treatment SGPT(ALT)-Placebo (n=92)	1 Participants	1 Participants	0 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Chemistry Test and Treatment SGOT(AST)-Famciclovir (n=190)	4 Participants	1 Participants	0 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Chemistry Test and Treatment SGOT(AST)-Placebo (n=92)	0 Participants	2 Participants	0 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Chemistry Test and Treatment Blood Urea Nitrogen-Famciclovir (n=196)	0 Participants	0 Participants	0 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Chemistry Test and Treatment Creatinine-Placebo (n=90)	5 Participants	0 Participants	0 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Chemistry Test and Treatment Bilirubin(total)-Famciclovir (n=192)	1 Participants	0 Participants	0 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Chemistry Test and Treatment Bilirubin(total)-Placebo (n=93)	1 Participants	0 Participants	0 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Chemistry Test and Treatment Amylase-Famciclovir (n=152)	6 Participants	2 Participants	0 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Chemistry Test and Treatment Amylase-Placebo (n=72)	3 Participants	1 Participants	0 Participants	0 Participants
The Number of Participants With Clinically Notable Shifts From Normal at Baseline by Chemistry Test and Treatment Lipase-Famciclovir (n=190)	2 Participants	3 Participants	1 Participants	0 Participants

Adverse Events

Famciclovir 1000 mg

Serious events: 2 serious events

Other events: 26 other events

Deaths: 0 deaths

Placebo Comparator

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Famciclovir 1000 mg n=206 participants at risk Famciclovir 1000 mg; twice a day for one day for treatment.	Placebo Comparator n=98 participants at risk Placebo twice a day for one day for treatment.
Cardiac disorders Heart Palpitations	0.49% 1/206 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).	0.00% 0/98 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).
Gastrointestinal disorders Pancreatitis	0.49% 1/206 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).	0.00% 0/98 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).
Injury, poisoning and procedural complications Radius Fracture	0.00% 0/206 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).	1.0% 1/98 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).
Respiratory, thoracic and mediastinal disorders Pulmonary Hypertension	0.49% 1/206 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).	0.00% 0/98 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).

Other adverse events

Other adverse events
Measure	Famciclovir 1000 mg n=206 participants at risk Famciclovir 1000 mg; twice a day for one day for treatment.	Placebo Comparator n=98 participants at risk Placebo twice a day for one day for treatment.
Nervous system disorders Headache	4.9% 10/206 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).	2.0% 2/98 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).
Gastrointestinal disorders Nausea	2.4% 5/206 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).	2.0% 2/98 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).
Gastrointestinal disorders Diarrhoea	1.5% 3/206 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).	1.0% 1/98 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).
Investigations Blood Pressure increased	0.97% 2/206 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).	0.00% 0/98 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).
Metabolism and nutrition disorders Decreased appetite	0.97% 2/206 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).	0.00% 0/98 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).
Gastrointestinal disorders Vomiting	0.97% 2/206 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).	0.00% 0/98 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).
Infections and infestations Upper respiratory tract infection	0.49% 1/206 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).	2.0% 2/98 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).
Gastrointestinal disorders Dry mouth	0.49% 1/206 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).	1.0% 1/98 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).
Reproductive system and breast disorders Adnexa uteri pain	0.00% 0/206 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).	1.0% 1/98 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).
Reproductive system and breast disorders Pelvic pain	0.00% 0/206 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).	1.0% 1/98 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).
Nervous system disorders Somnolence	0.00% 0/206 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).	1.0% 1/98 • 21 days AEs presented in this section are the AEs greater than 1% that occured in the treatment period. SAEs presented in this section are these that were reported either during the treatment or follow-up period (one SAE was reported during the follow-up period).

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