SPL7013, also known as VivaGel, is a type of medicine called a microbicide. Microbicides are substances that protect the body from infection by microorganisms such as bacteria, viruses, and fungi. Microbicides work by either destroying the microbes or preventing them from establishing an infection.
HIV/AIDS-Related Uses
SPL7013 is an investigational medicine that is not yet approved by the FDA for use outside of clinical trials. It is being studied for the prevention of HIV infection. SPL7013 is also being studied for the prevention of other sexually transmitted infections including herpes simplex virus-2 (HSV-2), the virus that causes genital herpes.This medicine does not cure HIV infection or AIDS and is being studied to reduce the risk of passing the virus to other people.
Dosage Form/Administration
SPL7013 comes in gel form and is applied vaginally with a single-use, prefilled vaginal applicator.
Recommended Daily Dose
SPL7013 has been given once or twice a day, every day, for up to 2 weeks in safety, tolerability, and acceptability studies. A 3% preparation of SPL7013 has been and is currently being evaluated in clinical trials.
Contraindications
Individuals should tell a doctor about any medical problems before taking this medicine.
Possible Side Effects
Along with its desired effects, SPL7013 can cause some unwanted effects. Although not all of these effects are known, stomach pain and painful urination have been reported.
Drug and Food Interactions
A doctor should be notified of any other medications being taken, including prescription, nonprescription (over-the-counter), or herbal medications.
Clinical Trials
Click here to search ClinicalTrials.gov for trials that use SPL7013.
Manufacturer Information
SPL7013
Starpharma Ltd
PO Box 6535
St. Kilda Road Central
Melbourne, Victoria,
Australia
Last Updated: October 6, 2008
Drug Description
SPL7013 is a lysine-based dendrimer with naphthalene disulfonic acid surface groups. [1] It is the active ingredient of VivaGel, a water-based vaginal microbicide gel. [2]
References
[1] Starpharma Overview: Dendrimers: Synthetic Macromolecular Pharmaceuticals, p. 2. Available at: http://www.starpharma.com/dendrimers.asp. Accessed 10/06/08.
[2] Starpharma Latest News: Vivagel Receives Fast Track Status From FDA [Press Release], January 9, 2006. Available at: http://www.starpharma.com/data/060109%20-%20VivaGel%20Fast%20Track%20Status.pdf. Accessed 10/06/08.
HIV/AIDS-Related Uses
SPL7013 is a potent inhibitor of HIV-1 in vitro and appears active against numerous strains. [1] It is being studied for use as the active ingredient in VivaGel, a vaginal microbicide, in the prevention of vaginal transmission of HIV and genital herpes. [2] VivaGel is at the expanded safety/Phase IIa stage of clinical development and was granted fast-track status by the FDA in January 2006. [3]
A study to test VivaGel's safety, acceptability, and ease of use in healthy, sexually active young women in the United States and Puerto Rico began enrollment in July 2007. [4] [5]
A Phase I/II clinical trial is currently underway to investigate the timescale over which VivaGel retains activity against HIV and HSV-2, and the trial will measure the level of antiviral activity retained by VivaGel after vaginal administration. [6]
References
[1] Starpharma Latest News: Vivagel Receives Fast Track Status From FDA [Press Release], January 9, 2006. Available at: http://www.starpharma.com/data/060109%20-%20VivaGel%20Fast%20Track%20Status.pdf. Accessed 10/06/08.
[2] Starpharma Latest News: U.S. NIH Funded Trial of VivaGel in Sexually Active Young Women Commences [Press Release], July 10, 2007. Available at: http://www.starpharma.com/data/070710%20%20VivaGel%20trial%20in%20sexually%20active%20young%20women.pdf. Accessed 10/06/08.
[3] Starpharma Latest News: Vivagel Receives Fast Track Status From FDA [Press Release], January 9, 2006. Available at: http://www.starpharma.com/data/060109%20-%20VivaGel%20Fast%20Track%20Status.pdf.
Accessed 10/06/08.
[4] Starpharma Latest News: U.S. NIH Funded Trial of VivaGel in Sexually Active Young Women Commences [Press Release], July 10, 2007. Available at: http://www.starpharma.com/data/070710%20%20VivaGel%20trial%20in%20sexually%20active%20young%20women.pdf. Accessed 10/06/08.
[5] ClinicalTrials.gov Safety and Acceptability of SPL7013 Gel (VivaGel) in Sexually Active Women. Available at: http://www.clinicaltrials.gov/ct/show/NCT00442910. Accessed 10/06/08.
[6] ClinicalTrials.gov Retention and Duration of Activity of SPL7013 (VivaGel®) After Vaginal Dosing. Available at: http://clinicaltrials.gov/ct2/show/NCT00740584. Accessed 10/06/08.
Dosing Information
Mode of Delivery
Intravaginal. [1]
Dosage Form
Phase I studies have evaluated VivaGel at concentrations of 0.5, 1, and 3% applied vaginally once daily for 7 days. In addition, a 5.0% vaginal gel has been evaluated in macaques. [2] [3]
VivaGel would be used via a single-use, prefilled vaginal applicator. [4]
References
[1] Starpharma Clinical Study Shows STARPHARMA's VivaGel is Safe; Appendix - SPL7013-001/CM4402 Phase 1 Clinical Trial Results [Press Release], December 16, 2004. Available at: http://www.starpharma.com/data/041216%20Clinical%20Study%20shows%20Starpharmas%20VivaGel%20is%20Safe.pdf. Accessed 10/06/08.
[2] Starpharma Clinical Study Shows STARPHARMA's VivaGel is Safe; Appendix - SPL7013-001/CM4402 Phase 1 Clinical Trial Results [Press Release], December 16, 2004. Available at: http://www.starpharma.com/data/041216%20Clinical%20Study%20shows%20Starpharmas%20VivaGel%20is%20Safe.pdf. Accessed 10/06/08.
[3] AIDS Res Hum Retroviruses 2005 Mar;21(3):207-13
[4] Starpharma VivaGel Information Sheet, p. 2. Available at: http://www.starpharma.com/vivagel.asp. Accessed 10/06/08.
Pharmacology
Dendrimers such as SPL7013 are polymers that contain a central core, interior branches, and terminal surface groups adapted to specific targets. SPL7013 has a polyanionic outer surface that provides for multiple target interactions. The active surface groups bind to gp120 proteins on HIV's surface, preventing CD4 receptor binding by healthy cells and thus blocking transmission of HIV to healthy cells. [1] [2]
A Phase I, double-blind, placebo-controlled trial evaluated the plasma absorption of SPL7013 in 36 healthy, sexually abstinent women. Women were assigned to 1 of 3 arms of 0.5, 1.0, and 3.0% gel, respectively, and all doses were administered once daily for 7 days. Eight women received active gel and four received placebo in each arm. Plasma samples after the first, third, fifth, and seventh doses showed no plasma SPL7013 levels, which confirmed localized activity of the drug. [3]
References
[1] Pharmaceutical Journal 2004 Nov 27;273:793-4
[2] AIDS Res Hum Retroviruses 2005 Mar;21(3):207-13
[3] Starpharma Clinical Study Shows STARPHARMA's VivaGel is Safe: Appendix - SPL7013-001/CM4402 Phase 1 Clinical Trial Results [Press Release], December 16, 2004. Available at: http://www.starpharma.com/data/041216%20Clinical%20Study%20shows%20Starpharmas%20VivaGel%20is%20Safe.pdf. Accessed 10/06/08.
Adverse Events/Toxicity
A Phase I placebo-controlled trial in healthy women evaluated the safety and tolerability of VivaGel. No serious or significant adverse events occurred with the 0.5, 1.0, or 3.0% doses. Mild adverse effects attributed to SPL7013 were abdominal pain and painful urination. Vaginal flora levels decreased similarly across all treatment and placebo groups but rebounded to normal levels by 7 days post-treatment. [1]
References
[1] Starpharma Clinical Study Shows STARPHARMA's VivaGel is Safe: Appendix - SPL7013-001/CM4402 Phase 1 Clinical Trial Results [Press Release], December 16, 2004. Available at: http://www.starpharma.com/data/041216%20Clinical%20Study%20shows%20Starpharmas%20VivaGel%20is%20Safe.pdf. Accessed 10/06/08.
Clinical Trials
Click here to search ClinicalTrials.gov for trials that use SPL7013.
Chemistry
CAS Name
L-Lysine, homopolymer [polylysine] [1]
CAS Number
676271-69-5 [2]
Molecular Weight
16,582 Da
Physical Description
SPL7013: white to off-white solid. [3]
VivaGel: water-based gel. [4]
Solubility
Both SPL7013 and VivaGel are highly water soluble. [5]
References
[1] MeSH Available at: http://www.nlm.nih.gov/mesh/MBrowser.html. Accessed 10/06/08.
[2] ChemIDplus Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 10/06/08.
[3] Microbicide Research Portal Candidate Products: VivaGel (SPL7013 Gel). Available at: https://secure.microbicide.org. Accessed 10/06/08.
[4] Microbicide Research Portal Candidate Products: VivaGel (SPL7013 Gel). Available at: https://secure.microbicide.org. Accessed 10/06/08.
[5] Microbicide Research Portal Candidate Products: VivaGel (SPL7013 Gel). Available at: https://secure.microbicide.org. Accessed 10/06/08.
Further Reading
Gong E, Matthews B, McCarthy T, Chu J, Holan G, Raff J, Sacks S. Evaluation of dendrimer SPL7013, a lead microbicide candidate against herpes simplex viruses. Antiviral Res. 2005 Dec;68(3):139-46. Epub 2005 Sep 27.
Jiang YH, Emau P, Cairns JS, Flanary L, Morton WR, McCarthy TD, Tsai CC. SPL7013 gel as a topical microbicide for prevention of vaginal transmission of SHIV89.6P in macaques. AIDS Res Hum Retroviruses. 2005 Mar;21(3):207-13.
McCarthy TD, Karellas P, Henderson SA, Giannis M, O'Keefe DF, Heery G, Paull JR, Matthews BR, Holan G. Dendrimers as drugs: discovery and preclinical and clinical development of dendrimer-based microbicides for HIV and STI prevention. Mol Pharm. 2005 Jul-Aug;2(4):312-8. Review.
Rosa Borges A, Schengrund CL. Dendrimers and antivirals: a review. Curr Drug Targets Infect Disord. 2005 Sep;5(3):247-54. Review.
Lackman-Smith C, Osterling C, Luckenbaugh K, Mankowski M, Snyder B, Lewis G, Paull J, Profy A, Ptak RG, Buckheit RW Jr, Watson KM, Cummins JE Jr, Sanders-Beer BE. Development of a comprehensive human immunodeficiency virus type 1 screening algorithm for discovery and preclinical testing of topical microbicides. Antimicrob Agents Chemother. 2008 May;52(5):1768-81. Epub 2008 Mar 3.
Rupp R, Rosenthal SL, Stanberry LR. VivaGel (SPL7013 Gel): a candidate dendrimer--microbicide for the prevention of HIV and HSV infection. Int J Nanomedicine. 2007;2(4):561-6.
Manufacturer Information
SPL7013
Starpharma Ltd
PO Box 6535
St. Kilda Road Central
Melbourne, Victoria,
Australia
Last Updated: October 6, 2008