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

A Multicenter, Randomized, Double-blind Study to Compare the Efficacy and Safety of Patient-initiated Famciclovir 1000 mg b.i.d. x 1 Day to Valacyclovir 500 mg b.i.d. x 3 Days in Immunocompetent Adults With Recurrent Genital Herpes

This study will assess the safety and efficacy of one-day famciclovir (1000 mg twice a day (b.i.d)) in reducing the duration of genital herpes lesions and the associated symptoms compared to three-day treatment with valacyclovir (500 mg capsule b.i.d).

Study Overview

• Status: Completed
• Conditions: Genital Herpes
• Intervention / Treatment: Drug: Famciclovir; Drug: Placebo matching valacyclovir; Drug: Valacyclovir; Drug: Placebo matching famciclovir

• Study Type: Interventional
• Enrollment (Actual): 1179
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Novartis Investigative Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B6
      • Novartis Investigational site
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2C7
      • Novartis Investigational site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0W3
      • Novartis Investigational site
  • Ontario
    • Markham, Ontario, Canada, L3P 1A8
      • Novartis Investigational site
    • Ottawa, Ontario, Canada, K1S 0G8
      • Novartis Investigational site
  • Quebec
    • Laval, Quebec, Canada, H7X 3S5
      • Novartis Investigational site
    • Montréal, Quebec, Canada, H2K 4L5
      • Novartis Investigational site
    • Montréal, Quebec, Canada, H3H IV4
      • Novartis Investigational site
    • Sainte-Foy, Quebec, Canada, G1V 4G2
      • Novartis Investigational site
• Germany
  • Augsburg, Germany, D-86179
    • Novartis Investigational site
  • Berlin, Germany
    • Novartis Investigational site
  • Freiburg, Germany, 79106
    • Novartis Investigational site
  • Rostock, Germany, D-18055
    • Novartis Investigational site
  • Wolfsburg, Germany, D-38440
    • Novartis Investigational site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Chandler, Arizona, United States, 85225
      • Novartis Investigative Site
    • Phoenix, Arizona, United States, 85015
      • Women's Health Research
    • Tucson, Arizona, United States, 85712
      • Quality of Life Medical & Research Center, LLC
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Burke Pharmaceutical Research
    • Jonesboro, Arkansas, United States, 72401
      • NEA Women's Clinic
    • Little Rock, Arkansas, United States, 72205
      • The Woman's Clinic
  • California
    • Burbank, California, United States, 91505
      • Providence Clinical Research
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associates
    • Sacramento, California, United States, 95825
      • Sacramento Research Medical Group
    • Sacramento, California, United States, 95831
      • North California Research Corp.
    • San Diego, California, United States, 92108
      • Medical Center for Clinical Research
    • San Francisco, California, United States, 94114
      • Conant Research
  • Colorado
    • Denver, Colorado, United States, 80262
      • Barbara Davis Center
    • Lakewood, Colorado, United States, 80228
      • Cohen & Womack, P.C.
  • Florida
    • Boynton Beach, Florida, United States, 33437
      • Visions Clinical Research
    • Clearwater, Florida, United States, 33759
      • Women's Medical Research Group, LLC
    • Miami, Florida, United States, 33156
      • International Research Association LLC
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Ctr.
    • Pembroke Pines, Florida, United States, 33024
      • University Clinical Research, Inc.
    • Pembroke Pines, Florida, United States, 33024
      • Avancia Research
    • West Palm Beach, Florida, United States, 33409
      • Palm Beach Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Mount Vernon Clinical Research
  • Indiana
    • Evansville, Indiana, United States, 47714
      • MediSphere Medical Research Center, LLC.
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Infectious Disease Research Group
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
  • Kentucky
    • Madisonville, Kentucky, United States, 42431
      • Common Wealth Biomedical Research
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • SNBL Clinical Pharmacology Center
  • Massachusetts
    • Springfield, Massachusetts, United States, 01107
      • Future Care Studies
  • Missouri
    • St. Louis, Missouri, United States, 63117
      • Clayton Research Institute
  • Montana
    • Billings, Montana, United States, 59101
      • Deaconess Billings Clinic Research Center
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Heartland Clinical Research, Inc.
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • UNC Clinical Research.
    • Winston-Salem, North Carolina, United States, 27103
      • Hawthorne Medical Research, Inc.
  • Ohio
    • Dayton, Ohio, United States, 45439
      • Providence Health Partners-Center for Clinical Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynne Health Science Institute
  • Oregon
    • Portland, Oregon, United States, 97210
      • Westover Heights Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Paddington Testing Co. Inc
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee Womens Hospital
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • S. Carolina Clinical Research Center
    • Florence, South Carolina, United States, 29501
      • Research Inc.
    • Simpsonville, South Carolina, United States, 29681
      • Palmetto Clinical Trial Services, LLC
  • Texas
    • Austin, Texas, United States, 78705
      • Benchmark Research
    • Dallas, Texas, United States, 75235
      • Renaissance Clinical Research and Hypertension Clinic
    • Houston, Texas, United States, 77058
      • Center For Clinical Studies
    • Houston, Texas, United States, 77030
      • Center for Clinical Studies (TX Medical Center)
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah-School of Medicine (Div. of Inf. Disease)
    • Sandy, Utah, United States, 84070
      • Salt Lake Women's Center/Physician's Research Options
  • Virginia
    • Richmond, Virginia, United States, 23225
      • Clinical Trials of Virginia, Inc.
  • Washington
    • Seattle, Washington, United States, 98122
      • University of Washington, Virology Research Clinic
    • Tacoma, Washington, United States, 98405
      • Liberty Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• At least 18 years old
• History of at least 4 recurrences of genital herpes in the preceding 12 months
• Lesions located on the external genitalia or anogenital region
• Willing to discontinue suppressive treatment
• Documented positive herpes simplex virus (HSV)
• General good health, and history of normal renal function

Exclusion Criteria:

• Women of childbearing potential not using approved form of contraceptive
• Pregnant or nursing women
• History of hypersensitivity to famciclovir, valacyclovir, or acyclovir
• Known to be immunosuppressed
• Known to have renal dysfunction
• Receiving anti-herpes therapy
• Known to have other genital tract disorders
• Known to have condition which could interfere with drug absorption

Additional protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Famciclovir; Famciclovir 500 mg tablet; Other Names: Famvir; Drug: Placebo matching valacyclovir; Valacyclovir placebo, matching in size, color and forms of valacyclovir capsule.
Active Comparator: Valacyclovir; Patients received Valacyclovir 500 mg capsule twice a day 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.	Drug: Valacyclovir; Valacyclovir 500 mg capsule; Other Names: Valtrex; Drug: Placebo matching famciclovir; Famciclovir placebo, matching in size, color and forms of famciclovir tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-assessed Time to Healing of All Non-aborted Genital Herpes Lesions	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.	72 hours after initiation of study medication up to Day 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Aborted Genital Herpes Lesions	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.	72 hours after initiation of study medication up to Day 20
Investigator-assessed Time to Healing of All (Non-aborted and Aborted) Genital Herpes Lesions	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.	72 hours after initiation of study medication up to Day 20
Time to Resolution of Symptoms Associated With Recurrent Genital Herpes	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.	72 hours after initiation of study medication up to Day 20
Number of Patients With a Second Recurrence of Genital Herpes	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.	Up to 6 months after investigator assessed healing of first recurrence of genital herpes
Time to a Second Recurrence of Genital Herpes	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: From the date of treatment initiation no earlier than the recurrence of genital herpes to the date of onset for the second recurrence, or; From the date of healing of non-aborted lesions or confirmation of aborted lesions to the date of onset for the second recurrence.	Up to 6 months after investigator assessed healing of first recurrence of genital herpes

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Bodsworth N, Fife K, Koltun W, Tyring S, Abudalu M, Prichard M, Hamed K. Single-day famciclovir for the treatment of genital herpes: follow-up results of time to next recurrence and assessment of antiviral resistance. Curr Med Res Opin. 2009 Feb;25(2):483-7. doi: 10.1185/03007990802664678.

Helpful Links

• eRecruitment

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: March 22, 2006
• First Submitted That Met QC Criteria: March 22, 2006
• First Posted (Estimate): March 24, 2006

Study Record Updates

• Last Update Posted (Estimate): June 30, 2011
• Last Update Submitted That Met QC Criteria: June 28, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: valacyclovir; Herpes simplex; genital herpes; famciclovir; Recurrent genital herpes
• Additional Relevant MeSH Terms: Skin Diseases; Virus Diseases; Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; DNA Virus Infections; Skin Diseases, Infectious; Skin Diseases, Viral; Herpesviridae Infections; Herpes Simplex; Herpes Genitalis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Valacyclovir; Famciclovir
• Other Study ID Numbers: CFAM810A2308