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Safety, Pharmacokinetics and Acceptability of PC-1005 for Vaginal Use

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Population Council
Sponsor:
Information provided by (Responsible Party):
Population Council
ClinicalTrials.gov Identifier:
NCT02033109
First received: January 8, 2014
Last updated: September 23, 2014
Last verified: September 2014
  Purpose

This Phase 1 clinical trial will evaluate MIV-150, a third generation non-nucleoside reverse transcriptase inhibitor, co-formulated with a potentially potent agent, zinc acetate for the prevention of HIV infection in women. This is the first in-human of PC-1005 (MIV-150/zinc acetate in a carrageenan gel), the first study in which females will be exposed to MIV-150, the first time MIV-150 will be administered topically, and the first time MIV-150 will be administered intravaginally.


Condition Intervention Phase
HIV
Drug: PC-1005
Drug: HEC gel
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase 1, Double-Blind, Parallel, Placebo-Controlled, Randomized Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Acceptability of PC-1005 Microbicide Gel Formulation in HIV-seronegative Women

Resource links provided by NLM:


Further study details as provided by Population Council:

Primary Outcome Measures:
  • Safety: adverse events, serious adverse events, physical exams, and clinical laboratory parameters [ Time Frame: 5 weeks for safety run-in study; 7 weeks for main study ] [ Designated as safety issue: Yes ]
    • Number and percent of participants with treatment emergent adverse events and adverse events, and medical significance of adverse events and serious adverse events
    • Number, percent and medical significance of abnormalities in physical exams, pelvic exams, and biopsies once product has been administered
    • Number, percent and medical significance of abnormalities in clinical laboratory parameters once product has been administered

  • Pharmacokinetics: evaluation of concentrations of MIV-150 in plasma [ Time Frame: Days 1, 2 and 3 (run-in) / Days 1, 8 and 14 (main study) ] [ Designated as safety issue: No ]
    • Area under the plasma/serum concentration curve
    • Peak plasma/serum concentration
    • Trough plasma/serum concentration
    • Time to peak plasma/serum concentration
    • Elimination half-life
    • Apparent clearance


Secondary Outcome Measures:
  • Assessment of acceptability and adherence of PC-1005 use in seronegative women (main study only) [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    Questionnaire, self-report, and applicators returned empty


Other Outcome Measures:
  • Exploratory: pharmacodynamics and immune mediators [ Time Frame: Day 1 (baseline, both run-in and main); Day 14 (post-dose, main study only) ] [ Designated as safety issue: No ]
    • Anti-HIV, anti-HSV, and anti-HPV activity in cervicovaginal lavages (CVL)
    • Immune mediators in CVL

  • Exploratory: MIV-150 and zinc levels in cervical tissue biopsies (main study only) [ Time Frame: Day 14 (post-dose) ] [ Designated as safety issue: No ]
    Additional cervical biopsy after the last dose

  • Exploratory: dye stain assay analysis [ Time Frame: Post-dose ] [ Designated as safety issue: No ]
    • Sensitivity, specificity, negative predictive values and positive predictive values of the dye stain assay, using applicators inserted under direct observation as the positive controls
    • Correlation between self-reported adherence, pharmacokinetics, pharmacodynamics, number of returned applicators and dye stain assay

  • Exploratory: pharmacokinetics evaluation of zinc in resum [ Time Frame: Days 1, 2 and 3 (run-in) / Days 1, 8 and 14 (main study) ] [ Designated as safety issue: No ]

Estimated Enrollment: 35
Study Start Date: June 2014
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PC-1005
  • 4.00 g dosed once daily for 3 days (safety run-in)
  • 4.00 g dosed once daily for 14 days (main study)
Drug: PC-1005
Intravaginal use
Other Name: MIV-150/zinc acetate in a carrageenan gel
Placebo Comparator: HEC gel
4.00 g dosed once daily for 14 days (main study only)
Drug: HEC gel
Other Names:
  • hydroxyethylcellulose gel
  • placebo gel

Detailed Description:

This study will begin with a safety run-in, which is an open label, single-arm safety run-in with 5 women receiving PC-1005 once daily for 3 consecutive days. Safety and pharmacokinetics will take place after each dose. the participants from the run-in will not be eligible for the main study.

The main study participants will be randomized 4:1 to the study gels: 24 randomized to PC-1005 (active) and 6 randomized to HEC gel (placebo). The study product will be applied vaginally once daily for 14 days with clinical and laboratory assessments at baseline (enrollment) and after the 1st, 2nd, 8th, 9th, and 14th doses, and a safety follow-up visit 7 days after the 14th dose.

Participants in the run-in and main study will be requested to be sexually abstinent starting immediately after the Screening Visit until study exit.

  Eligibility

Ages Eligible for Study:   19 Years to 49 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Women between 19 and 49 years of age, inclusive
  • Willing and able to provide written informed consent
  • Healthy, based on medical history, vital signs, physical examination, urinalysis, laboratory evaluations for genital infections and laboratory evaluations for hematology, liver and renal function with a BMI ≥18 kg/m^2 and ≤32 kg/m^2
  • HIV-negative as determined by HIV ELISA test at screening
  • Hepatitis B and C negative at screening
  • Rapid plasma reagin negative at screening
  • If HSV-2 positive, must be free from outbreaks for at least 6 months prior to screening
  • In the absence of the use of exogenous hormone(s), have a self-reported regular menstrual cycle, defined as having a minimum of 21 days and a maximum of 35 days between menses
  • Normal Pap test at screening
  • Agrees to use one form of effective contraception for the duration of the trial
  • Willing to abstain from sexual intercourse/activity including receptive vaginal, oral, digital, and anal intercourse, and the use of any vaginal products including tampons, male and female condoms, contraceptive sponges, diaphragms, cervical caps, douches, lubricants, and vibrators/dildos starting from the Screening Visit through Study Exit
  • Agrees to not participate in any other clinical research trial for the duration of this trial

Exclusion Criteria:

  • History of or known sensitivity/allergy to any component of either study product
  • Currently pregnant or breast-feeding, or within 3 months of last pregnancy outcome
  • Participation in any other clinical research trial involving investigational or marketed products currently or within two months of participation prior to screening, including any trial of a spermicide, microbicide and/or drug
  • Diagnosed with or treated for any STI (other than HSV) or pelvic inflammatory disease in the last 3 months
  • Positive test for Neisseria gonorrhea, Chlamydia trachomatis, or Trichomonas vaginalis
  • Symptomatic vulvovaginal candidiasis, bacterial vaginosis (BV), or urinary tract infection (UTI) at screening
  • Presence of any clinically significant genital epithelial findings such as abrasions, ulcerations, lacerations, or vesicles suspicious for STIs at screening
  • Presence of any other clinically significant abnormal physical finding on the vulva, vaginal walls or cervix at screening
  • Any clinically significant abnormal hematology, chemistry or urinalysis findings at screening
  • Any chronic (excluding HSV-2) or progressive disease (including any known history of cancer, diabetes, cardiac disease, autoimmune disease, blood dyscrasias, or Wilson's disease), or signs of cardiovascular disease, or renal failure, even controlled with medication
  • History of hysterectomy or menopause
  • Use of excluded contraceptive methods including Nuvaring®, condoms (male or female), contraceptive sponge, diaphragm, or cervical cap (Safety Run-in and Main study)
  • History of gynecological surgery or procedure within past 2 months
  • History of uterine prolapse, undiagnosed vaginal bleeding or urethral obstruction within the last 3 months, including break-through bleeding requiring sanitary protection
  • Known current drug abuse, including illicit drugs, or alcohol abuse
  • Any other condition(s) that, in the opinion of the Investigator, might interfere with adherence to trial requirements or evaluation of the trial objectives
  • Unable to comply with study requirements, including but not limited to, attending all study visits, using the gel as directed, observing abstinence throughout the study and use of effective contraceptives, limiting alcoholic beverages to 2 per day and caffeine to no more than 6 servings per day
  • History of latex allergy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02033109

Contacts
Contact: Barbara Friedland, MPH 212-339-0629

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Craig J Hoesley, MD    205-934-3365      
Principal Investigator: Craig J Hoesley, MD         
Sponsors and Collaborators
Population Council
Investigators
Principal Investigator: Craig J Hoesley, MD University of Alabama at Birmingham
Study Chair: George W Creasy, MD Population Council
Study Director: Barbara Friedland, MPH Population Council
  More Information

No publications provided

Responsible Party: Population Council
ClinicalTrials.gov Identifier: NCT02033109     History of Changes
Other Study ID Numbers: Population Council #558
Study First Received: January 8, 2014
Last Updated: September 23, 2014
Health Authority: United States: Food and Drug Administration

ClinicalTrials.gov processed this record on November 23, 2014