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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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HIV

Intervention / Treatment
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* Drug: PC-1005
* Drug: HEC gel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PC-1005<br>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<br>* Intravaginal use<br>* Other names: MIV-150/zinc acetate in a carrageenan gel;|
| Placebo Comparator: HEC gel<br>4.00 g dosed once daily for 14 days (main study only) | Drug: HEC gel<br> <br> * Other names: placebo gel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: adverse events, serious adverse events, physical exams, and clinical laboratory parameters | 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 | 5 weeks for safety run-in study; 7 weeks for main study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of acceptability and adherence of PC-1005 use in seronegative women (main study only) | Questionnaire, self-report, and applicators returned empty | 14 days |