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[PMID]: | 27437826 |
[Au] Autor: | Friedland BA; Hoesley CJ; Plagianos M; Hoskin E; Zhang S; Teleshova N; Alami M; Novak L; Kleinbeck KR; Katzen LL; Zydowsky TM; Fernández-Romero JA; Creasy GW |
[Ad] Endereço: | *The Population Council, New York, NY; and †University of Alabama at Birmingham; Birmingham, AL. |
[Ti] Título: | First-in-Human Trial of MIV-150 and Zinc Acetate Coformulated in a Carrageenan Gel: Safety, Pharmacokinetics, Acceptability, Adherence, and Pharmacodynamics. |
[So] Source: | J Acquir Immune Defic Syndr;73(5):489-496, 2016 Dec 15. | [Is] ISSN: | 1944-7884 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | OBJECTIVE: To evaluate the safety and pharmacokinetics of MIV-150 and zinc acetate in a carrageenan gel (PC-1005). Acceptability, adherence, and pharmacodynamics were also explored. DESIGN: A 3-day open-label safety run-in (n = 5) preceded a placebo-controlled, double-blind trial in healthy, HIV-negative, abstinent women randomized (4:1) to vaginally apply 4 mL of PC-1005 or placebo once daily for 14 days. METHODS: Assessments included physical examinations, safety labs, colposcopy, biopsies, cervicovaginal lavages (CVLs), and behavioral questionnaires. MIV-150 (plasma, CVL, tissue), zinc (plasma, CVL), and carrageenan (CVL) concentrations were determined with LC-MS/MS, ICP-MS, and ELISA, respectively. CVL antiviral activity was measured using cell-based assays. Safety, acceptability, and adherence were analyzed descriptively. Pharmacokinetic parameters were calculated using noncompartmental techniques and actual sampling times. CVL antiviral EC50 values were calculated using a dose-response inhibition analysis. RESULTS: Participants (n = 20) ranged from 19-44 years old; 52% were black or African American. Among those completing the trial (13/17, PC-1005; 3/3, placebo), 11/17 reported liking the gel overall; 7 recommended reducing the volume. Adverse events, which were primarily mild and/or unrelated, were comparable between groups. Low systemic MIV-150 levels were observed, without accumulation. Plasma zinc levels were unchanged from baseline. Seven of seven CVLs collected 4-hour postdose demonstrated antiviral (HIV, human papillomavirus) activity. High baseline CVL anti-herpes-simplex virus type-2 (HSV-2) activity precluded assessment of postdose activity. CONCLUSIONS: PC-1005 used vaginally for 14 days was well tolerated. Low systemic levels of MIV-150 were observed. Plasma zinc levels were unchanged. Postdose CVLs had anti-HIV and anti-human papillomavirus activity. These data warrant further development of PC-1005 for HIV and sexually transmitted infection prevention. |
[Mh] Termos MeSH primário: |
Antivirais/administração & dosagem Carragenina/administração & dosagem Géis/administração & dosagem Profilaxia Pré-Exposição/métodos Piridinas/administração & dosagem Doenças Virais Sexualmente Transmissíveis/prevenção & controle Ureia/análogos & derivados Acetato de Zinco/administração & dosagem
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[Mh] Termos MeSH secundário: |
Administração Intravaginal Adulto Antivirais/efeitos adversos Antivirais/farmacocinética Carragenina/efeitos adversos Carragenina/farmacocinética Cromatografia Líquida Método Duplo-Cego Feminino Géis/efeitos adversos Seres Humanos Adesão à Medicação Aceitação pelo Paciente de Cuidados de Saúde Placebos/administração & dosagem Piridinas/efeitos adversos Piridinas/farmacocinética Espectrometria de Massas em Tandem Ureia/administração & dosagem Ureia/efeitos adversos Ureia/farmacocinética Adulto Jovem Acetato de Zinco/efeitos adversos Acetato de Zinco/farmacocinética
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[Pt] Tipo de publicação: | CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL |
[Nm] Nome de substância:
| 0 (Antiviral Agents); 0 (Gels); 0 (MIV 150); 0 (Placebos); 0 (Pyridines); 8W8T17847W (Urea); 9000-07-1 (Carrageenan); FM5526K07A (Zinc Acetate) |
[Em] Mês de entrada: | 1706 |
[Cu] Atualização por classe: | 170606 |
[Lr] Data última revisão:
| 170606 |
[Sb] Subgrupo de revista: | IM; X |
[Da] Data de entrada para processamento: | 160721 |
[St] Status: | MEDLINE |
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