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First-in-Human Trial of MIV-150 and Zinc Acetate Coformulated in a Carrageenan Gel: Safety, Pharmacokinetics, Acceptability, Adherence, and Pharmacodynamics.

First-in-Human Trial of MIV-150 and Zinc Acetate Coformulated in a Carrageenan Gel: Safety, Pharmacokinetics, Acceptability, Adherence, and Pharmacodynamics.
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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,


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, (click to view)

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,

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Journal of acquired immune deficiency syndromes (1999) 73(5) 489-496

Abstract
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.

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