- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT02053142
Acyclovir Therapy for Genital Herpes Ulcers in HIV Negative African Women
13 september 2017 uppdaterad av: University of North Carolina, Chapel Hill
Prospective Study of Pharmacokinetics, Clinical and Virologic Response to Acyclovir Episodic Therapy for Genital Herpes Ulcers in HIV Negative African Women
This is a prospective study to evaluate the pharmacokinetics, clinical and virologic response to acyclovir episodic therapy for genital herpes ulcers in HIV negative African women.
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Detaljerad beskrivning
This is a two-part study designed to measure the Area Under the Curve (AUC) from a single dose of acyclovir 400mg in 60 African HIV-negative heterosexual women who have a history of genital ulcer disease (GUD), are HSV-2 seropositive and HIV-1 seronegative.
The study will also examine the time to healing of genital lesion and duration of HSV shedding from GUD among 90 HIV negative African women who have a history of GUD and are Herpes Simplex Virus (HSV)-2 seropositive and HIV-1 seronegative randomized in a 2:1 ratio to receive episodic acyclovir or matching placebo.
Studietyp
Interventionell
Inskrivning (Faktisk)
74
Fas
- Inte tillämpbar
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
-
-
-
Lusaka, Zambia
- Centre for Infectious Disease Research in Zambia
-
-
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år till 50 år (Vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Kvinna
Beskrivning
Inclusion Criteria:
- HIV negative as determined by concordant rapid testing
- HSV-2 seropositive (Focus HerpeSelect EIA >3.4)
- At least one prior occurrence of GUD
- 18 to 50 years of age
Exclusion Criteria:
- Current use, or use within the past 7 days, of acyclovir, valacyclovir, or famciclovir
- Prior hypersensitivity and/or allergic reaction to acyclovir
- Use of probenecid, which prolongs renal excretion of acyclovir
- Current use, or use within the past 28 days, of an investigational agent
- Currently pregnant or nursing
- Currently plan to become pregnant during the next 3 months
- Currently consume, on average, more than 7 drinks of alcohol per week (for Part I)
- Current use of more than 20 cigarettes daily (for Part I)
- Any condition that in the opinion of the investigator will interfere with successful completion of all study procedures.
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Fyrdubbla
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
---|---|
Experimentell: Part 1 PK
400mg dose of acyclovir taken orally, followed by 2 ml blood plasma collection at 1,2,4,6 and 8 hours.
|
Single dose of acyclovir 200mg was given for pk study
|
Aktiv komparator: Acyclovir
400 mg Acyclovir three times daily for 5 days
|
Single dose of acyclovir 200mg was given for pk study
|
Placebo-jämförare: Placebo
Placebo three times daily for 5 days
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Area under the Curve (AUC)
Tidsram: 0, 2, 3, 4, 6 and 8 hours post acyclovir administration
|
Blood will be drawn for pharmacokinetic measures to determine whether there is a difference in African women vs. the existing AUC data for women and men in North America and Europe.
|
0, 2, 3, 4, 6 and 8 hours post acyclovir administration
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Time to re-epithelization and time to cessation of HSV shedding
Tidsram: days 1-5, 7, 9, 11 and 13
|
Daily assessment of response of genital lesions over 13 days by time to healing and duration of HSV shedding during acyclovir 400mg orally three times daily versus placebo three times daily for 5 days.
|
days 1-5, 7, 9, 11 and 13
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Samarbetspartners
Utredare
- Huvudutredare: Stewart Reid, MD, Centre for Infectious Disease Research in Zambia
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Allmänna publikationer
- Kimberlin DF, Weller S, Whitley RJ, Andrews WW, Hauth JC, Lakeman F, Miller G. Pharmacokinetics of oral valacyclovir and acyclovir in late pregnancy. Am J Obstet Gynecol. 1998 Oct;179(4):846-51. doi: 10.1016/s0002-9378(98)70176-0.
- Reichman RC, Badger GJ, Mertz GJ, Corey L, Richman DD, Connor JD, Redfield D, Savoia MC, Oxman MN, Bryson Y, et al. Treatment of recurrent genital herpes simplex infections with oral acyclovir. A controlled trial. JAMA. 1984 Apr 27;251(16):2103-7.
- Nilsen AE, Aasen T, Halsos AM, Kinge BR, Tjotta EA, Wikstrom K, Fiddian AP. Efficacy of oral acyclovir in the treatment of initial and recurrent genital herpes. Lancet. 1982 Sep 11;2(8298):571-3. doi: 10.1016/s0140-6736(82)90658-4.
- Celum, C., et al., HSV-2 Suppressive Therapy for Prevention of HIV Acquisition: Results of HPTN 039. The Lancet, in press.
- Reitano M, Tyring S, Lang W, Thoming C, Worm AM, Borelli S, Chambers LO, Robinson JM, Corey L. Valaciclovir for the suppression of recurrent genital herpes simplex virus infection: a large-scale dose range-finding study. International Valaciclovir HSV Study Group. J Infect Dis. 1998 Sep;178(3):603-10. doi: 10.1086/515385.
- Gupta R, Wald A, Krantz E, Selke S, Warren T, Vargas-Cortes M, Miller G, Corey L. Valacyclovir and acyclovir for suppression of shedding of herpes simplex virus in the genital tract. J Infect Dis. 2004 Oct 15;190(8):1374-81. doi: 10.1086/424519. Epub 2004 Sep 20.
- Watson-Jones D, Weiss HA, Rusizoka M, Changalucha J, Baisley K, Mugeye K, Tanton C, Ross D, Everett D, Clayton T, Balira R, Knight L, Hambleton I, Le Goff J, Belec L, Hayes R; HSV trial team; Steering and Data Monitoring Committees. Effect of herpes simplex suppression on incidence of HIV among women in Tanzania. N Engl J Med. 2008 Apr 10;358(15):1560-71. doi: 10.1056/NEJMoa0800260. Epub 2008 Mar 12. Erratum In: N Engl J Med. 2010 Apr 15;362(15):1450.
- Blum, M., et al., The bioavailability and pharmacokinetics of ZOVIRAX 200 mg capsules vs solution in normal volunteers at risk of developing herpes simplex virus infections (Protocol P12-83). Burroughs Wellcome Document No. TEIN/82/0001.
- De Miranda, P. and D. Page, Systemic absorption and pharmacokinetics of acyclovir (ZOVIRAX) when administered orally in multiple doses of 600 mg to immunocompromised patients with herpes infections (Protocol 12-30, Dr. R. Whitley). Burroughs Wellcome Document No. TEIN/82/0007.
- De Miranda, P. and D. Page, Systemic absorption and pharmacokinetics of acyclovir (ZOVIRAX) when administered orally in multiple doses of 800 mg to immunocompromised patients with herpes infections (Protocol 12-30, Dr. R. Whitley) Burroughs Wellcome Document No. TEIN/83/0001.
- Blum, M. and S. Liao, Pharmacokinetics and relative bioavailability of acyclovir capsules (ZOVIRAX) after multiple oral doses (Interim summary of study P12-32) amendment). Burroughs Wellcome Document No. TYBH/83/0001.
- Amini H, Javan M, Gazerani P, Ghaffari A, Ahmadiani A. Lack of bioequivalence between two aciclovir tablets in healthy subjects. Clin Drug Investig. 2008;28(1):47-53. doi: 10.2165/00044011-200828010-00006.
- Bahrami G, Mirzaeei Sh, Kiani A. Determination of acyclovir in human serum by high-performance liquid chromatography using liquid-liquid extraction and its application in pharmacokinetic studies. J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Feb 25;816(1-2):327-31. doi: 10.1016/j.jchromb.2004.11.038.
- Palma-Aguirre JA, Absalon-Reyes JA, Novoa-Heckel G, de Lago A, Oliva I, Rodriguez Z, Gonzalez-de la Parra M, Burke-Fraga V, Namur S. Bioavailability of two oral suspension and two oral tablet formulations of acyclovir 400 mg: two single-dose, open-label, randomized, two-period crossover comparisons in healthy Mexican adult subjects. Clin Ther. 2007 Jun;29(6):1146-52. doi: 10.1016/j.clinthera.2007.06.007.
- Vergin H, Kikuta C, Mascher H, Metz R. Pharmacokinetics and bioavailability of different formulations of aciclovir. Arzneimittelforschung. 1995 Apr;45(4):508-15.
- Landowski CP, Sun D, Foster DR, Menon SS, Barnett JL, Welage LS, Ramachandran C, Amidon GL. Gene expression in the human intestine and correlation with oral valacyclovir pharmacokinetic parameters. J Pharmacol Exp Ther. 2003 Aug;306(2):778-86. doi: 10.1124/jpet.103.051011. Epub 2003 May 15.
- Steingrimsdottir H, Gruber A, Palm C, Grimfors G, Kalin M, Eksborg S. Bioavailability of aciclovir after oral administration of aciclovir and its prodrug valaciclovir to patients with leukopenia after chemotherapy. Antimicrob Agents Chemother. 2000 Jan;44(1):207-9. doi: 10.1128/AAC.44.1.207-209.2000.
- Frenkel LM, Brown ZA, Bryson YJ, Corey L, Unadkat JD, Hensleigh PA, Arvin AM, Prober CG, Connor JD. Pharmacokinetics of acyclovir in the term human pregnancy and neonate. Am J Obstet Gynecol. 1991 Feb;164(2):569-76. doi: 10.1016/s0002-9378(11)80023-2.
- Haddad J, Langer B, Astruc D, Messer J, Lokiec F. Oral acyclovir and recurrent genital herpes during late pregnancy. Obstet Gynecol. 1993 Jul;82(1):102-4.
- Stone KM, Whittington WL. Treatment of genital herpes. Rev Infect Dis. 1990 Jul-Aug;12 Suppl 6:S610-9. doi: 10.1093/clinids/12.supplement_6.s610.
- Spruance SL, Jones TM, Blatter MM, Vargas-Cortes M, Barber J, Hill J, Goldstein D, Schultz M. High-dose, short-duration, early valacyclovir therapy for episodic treatment of cold sores: results of two randomized, placebo-controlled, multicenter studies. Antimicrob Agents Chemother. 2003 Mar;47(3):1072-80. doi: 10.1128/AAC.47.3.1072-1080.2003.
- Bodsworth NJ, Crooks RJ, Borelli S, Vejlsgaard G, Paavonen J, Worm AM, Uexkull N, Esmann J, Strand A, Ingamells AJ, Gibb A. Valaciclovir versus aciclovir in patient initiated treatment of recurrent genital herpes: a randomised, double blind clinical trial. International Valaciclovir HSV Study Group. Genitourin Med. 1997 Apr;73(2):110-6. doi: 10.1136/sti.73.2.110.
- Sacks SL, Aoki FY, Diaz-Mitoma F, Sellors J, Shafran SD. Patient-initiated, twice-daily oral famciclovir for early recurrent genital herpes. A randomized, double-blind multicenter trial. Canadian Famciclovir Study Group. JAMA. 1996 Jul 3;276(1):44-9.
- Spruance SL, Tyring SK, DeGregorio B, Miller C, Beutner K. A large-scale, placebo-controlled, dose-ranging trial of peroral valaciclovir for episodic treatment of recurrent herpes genitalis. Valaciclovir HSV Study Group. Arch Intern Med. 1996 Aug 12-26;156(15):1729-35.
- Aoki FY, Tyring S, Diaz-Mitoma F, Gross G, Gao J, Hamed K. Single-day, patient-initiated famciclovir therapy for recurrent genital herpes: a randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2006 Jan 1;42(1):8-13. doi: 10.1086/498521. Epub 2005 Nov 23. Erratum In: Clin Infect Dis. 2006 Feb 15;42(4):588.
- Wald A, Carrell D, Remington M, Kexel E, Zeh J, Corey L. Two-day regimen of acyclovir for treatment of recurrent genital herpes simplex virus type 2 infection. Clin Infect Dis. 2002 Apr 1;34(7):944-8. doi: 10.1086/339325. Epub 2002 Feb 20.
- Leone PA, Trottier S, Miller JM. Valacyclovir for episodic treatment of genital herpes: a shorter 3-day treatment course compared with 5-day treatment. Clin Infect Dis. 2002 Apr 1;34(7):958-62. doi: 10.1086/339326. Epub 2002 Feb 20.
- Wald A, Huang ML, Carrell D, Selke S, Corey L. Polymerase chain reaction for detection of herpes simplex virus (HSV) DNA on mucosal surfaces: comparison with HSV isolation in cell culture. J Infect Dis. 2003 Nov 1;188(9):1345-51. doi: 10.1086/379043. Epub 2003 Oct 31.
- Wald A, Zeh J, Selke S, Warren T, Ryncarz AJ, Ashley R, Krieger JN, Corey L. Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons. N Engl J Med. 2000 Mar 23;342(12):844-50. doi: 10.1056/NEJM200003233421203.
- Diaz-Mitoma F, Ruben M, Sacks S, MacPherson P, Caissie G. Detection of viral DNA to evaluate outcome of antiviral treatment of patients with recurrent genital herpes. J Clin Microbiol. 1996 Mar;34(3):657-63. doi: 10.1128/jcm.34.3.657-663.1996.
- Leone P, Warren T, Hamed K, Fife K, Wald A. Famciclovir reduces viral mucosal shedding in HSV-seropositive persons. Sex Transm Dis. 2007 Nov;34(11):900-7. doi: 10.1097/OLQ.0b013e318063c749.
- Bavaro JB, Drolette L, Koelle DM, Almekinder J, Warren T, Tyring S, Wald A. One-day regimen of valacyclovir for treatment of recurrent genital herpes simplex virus 2 infection. Sex Transm Dis. 2008 Apr;35(4):383-6. doi: 10.1097/OLQ.0b013e31815e4190.
- Goldberg LH, Kaufman R, Conant MA, Sperber J, Allen ML, Illeman M, Chapman S. Oral acyclovir for episodic treatment of recurrent genital herpes. Efficacy and safety. J Am Acad Dermatol. 1986 Aug;15(2 Pt 1):256-64. doi: 10.1016/s0190-9622(86)70165-5.
- Tyring SK, Douglas JM Jr, Corey L, Spruance SL, Esmann J. A randomized, placebo-controlled comparison of oral valacyclovir and acyclovir in immunocompetent patients with recurrent genital herpes infections. The Valaciclovir International Study Group. Arch Dermatol. 1998 Feb;134(2):185-91. doi: 10.1001/archderm.134.2.185.
- Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS. 2006 Jan 2;20(1):73-83. doi: 10.1097/01.aids.0000198081.09337.a7.
- Rebbapragada A, Wachihi C, Pettengell C, Sunderji S, Huibner S, Jaoko W, Ball B, Fowke K, Mazzulli T, Plummer FA, Kaul R. Negative mucosal synergy between Herpes simplex type 2 and HIV in the female genital tract. AIDS. 2007 Mar 12;21(5):589-98. doi: 10.1097/QAD.0b013e328012b896.
- Belec, L., et al. Impact of HSV-2 Episodic Therapy on HIV-1 and HSV-2 Genital Shedding and Ulcer Healing Among Women in Ghana and the Central African Republic: Randomized Double-Blind Placebo-Controlled trial. in XXth Annual Conference of the International Union Against STI. 2006. Versailles, France.
- Paz-Bailey, G., et al. Impact of Episodic Acyclovir Therapy on Genital Ulcer Duration and HIV Shedding from Herpetic Ulcers Among Men in South Africa. in 17th International Society for STD Research Meeting. 2007. Seattle, Washington, USA.
Användbara länkar
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 januari 2009
Primärt slutförande (Faktisk)
1 december 2009
Avslutad studie (Faktisk)
1 december 2009
Studieregistreringsdatum
Först inskickad
31 januari 2014
Först inskickad som uppfyllde QC-kriterierna
31 januari 2014
Första postat (Uppskatta)
3 februari 2014
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
15 september 2017
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
13 september 2017
Senast verifierad
1 december 2014
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- CIDRZ 1208/IRB12-0390
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .
Kliniska prövningar på Ulcers of Female Genital Organs
-
AbbVie (prior sponsor, Abbott)AlmedisAvslutad
-
Phillip Song, MDIndragenGranulom | Kontakta Ulcer of Vocal Folds | Granulom av stämband | Granulom, larynxFörenta staterna
-
NPO PetrovaxAktiv, inte rekryterandeExtern Genital EndometriosRyska Federationen
-
University of TennesseeUniversity of Tennessee West Cancer CenterAvslutad
-
Wayne State UniversitySt Vincent's Hospital; University of California, San Francisco FresnoAvslutadVårta, Genital
-
ProbiSearch SLAvslutadUtvärdera användningen av en ny probiotisk stam hos par med fertilitetsproblem och dysbios. (PROFEC)Infertilitet | Vaginal flora obalans | Genital störningSpanien
-
UBP Greater China (Shanghai) Co., LtdHar inte rekryterat ännu
-
UBP Greater China (Shanghai) Co., LtdHar inte rekryterat ännu
-
EMSAvslutad
-
Starpharma Pty LtdNational Institute of Allergy and Infectious Diseases (NIAID)AvslutadHIV-infektioner | HSV-2 Genital HerpesAustralien
Kliniska prövningar på Placebo
-
SamA Pharmaceutical Co., LtdOkändAkut bronkit | Akut övre luftvägsinfektionKorea, Republiken av
-
National Institute on Drug Abuse (NIDA)AvslutadAnvändning av cannabisFörenta staterna
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyAvslutadManliga försökspersoner med typ II-diabetes (T2DM)Tyskland
-
Heptares Therapeutics LimitedAvslutadFarmakokinetik | SäkerhetsfrågorStorbritannien
-
Longeveron Inc.AvslutadHypoplastiskt vänsterhjärtsyndromFörenta staterna
-
Texas A&M UniversityNutraboltAvslutadGlucose and Insulin Response
-
Regado Biosciences, Inc.AvslutadFrisk volontärFörenta staterna
-
ItalfarmacoAvslutadBeckers muskeldystrofiNederländerna, Italien
-
Universidade Estadual de LondrinaConselho Nacional de Desenvolvimento Científico e Tecnológico; Coordination...AvslutadVassleproteintillskott associerat med motståndsträning på hälsoindikatorer hos tränade äldre kvinnorFriska | Kroppssammansättning