PMID- 27437826
OWN - NLM
STAT- MEDLINE
DCOM- 20170606
LR  - 20200930
IS  - 1944-7884 (Electronic)
IS  - 1525-4135 (Print)
IS  - 1525-4135 (Linking)
VI  - 73
IP  - 5
DP  - 2016 Dec 15
TI  - First-in-Human Trial of MIV-150 and Zinc Acetate Coformulated in a Carrageenan 
      Gel: Safety, Pharmacokinetics, Acceptability, Adherence, and Pharmacodynamics.
PG  - 489-496
AB  - 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.
FAU - Friedland, Barbara A
AU  - Friedland BA
AD  - *The Population Council, New York, NY; and daggerUniversity of Alabama at Birmingham; 
      Birmingham, AL.
FAU - Hoesley, Craig J
AU  - Hoesley CJ
FAU - Plagianos, Marlena
AU  - Plagianos M
FAU - Hoskin, Elena
AU  - Hoskin E
FAU - Zhang, Shimin
AU  - Zhang S
FAU - Teleshova, Natalia
AU  - Teleshova N
FAU - Alami, Mohcine
AU  - Alami M
FAU - Novak, Lea
AU  - Novak L
FAU - Kleinbeck, Kyle R
AU  - Kleinbeck KR
FAU - Katzen, Lauren L
AU  - Katzen LL
FAU - Zydowsky, Thomas M
AU  - Zydowsky TM
FAU - Fernandez-Romero, Jose A
AU  - Fernandez-Romero JA
FAU - Creasy, George W
AU  - Creasy GW
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - J Acquir Immune Defic Syndr
JT  - Journal of acquired immune deficiency syndromes (1999)
JID - 100892005
RN  - 0 (Antiviral Agents)
RN  - 0 (Gels)
RN  - 0 (MIV 150)
RN  - 0 (Placebos)
RN  - 0 (Pyridines)
RN  - 8W8T17847W (Urea)
RN  - 9000-07-1 (Carrageenan)
RN  - FM5526K07A (Zinc Acetate)
SB  - IM
MH  - Administration, Intravaginal
MH  - Adult
MH  - Antiviral Agents/*administration & dosage/adverse effects/pharmacokinetics
MH  - Carrageenan/*administration & dosage/adverse effects/pharmacokinetics
MH  - Chromatography, Liquid
MH  - Double-Blind Method
MH  - Female
MH  - Gels/*administration & dosage/adverse effects
MH  - Humans
MH  - Medication Adherence
MH  - Patient Acceptance of Health Care
MH  - Placebos/administration & dosage
MH  - Pre-Exposure Prophylaxis/*methods
MH  - Pyridines/*administration & dosage/adverse effects/pharmacokinetics
MH  - Sexually Transmitted Diseases, Viral/*prevention & control
MH  - Tandem Mass Spectrometry
MH  - Urea/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacokinetics
MH  - Young Adult
MH  - Zinc Acetate/*administration & dosage/adverse effects/pharmacokinetics
PMC - PMC5172848
COIS- The authors have no conflicts of interest to disclose.
EDAT- 2016/07/21 06:00
MHDA- 2017/06/07 06:00
PMCR- 2016/12/20
CRDT- 2016/07/21 06:00
PHST- 2016/07/21 06:00 [pubmed]
PHST- 2017/06/07 06:00 [medline]
PHST- 2016/07/21 06:00 [entrez]
PHST- 2016/12/20 00:00 [pmc-release]
AID - QAIV16353 [pii]
AID - 10.1097/QAI.0000000000001136 [doi]
PST - ppublish
SO  - J Acquir Immune Defic Syndr. 2016 Dec 15;73(5):489-496. doi: 
      10.1097/QAI.0000000000001136.