A Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of Antimicrobial Peptide PL-18 Vaginal Suppositories in Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- Dose 1 to 5 of Antimicrobial Peptide PL-18 Vaginal Suppositories
- Conditions
- Colpomycosis
- Sponsor
- Protelight Pharmaceuticals Australia PTY LTD
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Characterize safety profile of Antimicrobial Peptide PL-18 Vaginal Suppositories about the incidence of treatment emergent adverse events
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a Single-center, Randomized, Double-blind, Placebo-controlled Phase I Study to Evaluate the Safety, Tolerability and PK Profiles of Single and Multiple Ascending Doses of Antimicrobial Peptide PL-18 Vaginal Suppositories.
Detailed Description
Subjects who provide written informed consent to participate voluntarily in the clinical study will be screened. Eligible subjects will be sequentially enrolled into the above five sequential cohorts and randomized to receive PL-18 (cohort 1: n=8; cohort 2/3/4/5: n=6) or matching placebo (n=2). Subjects will be observed for 3 days after a single dose and receive PL-18 or placebo, once daily, for 6 consecutive days, if no grade ≥2 drug-related adverse events (AEs) occur. During the study, PK sample collection, physical examination, vital signs, laboratory tests, electrocardiography (ECG) and tolerance evaluation will be performed based on the protocol schedule. To ensure the safety of the subjects, two sentinel subjects will be enrolled first in each cohort; one subject will be randomized to receive PL-18, and the other subject randomized to receive placebo. The safety data of the two sentinel subjects from initiation of single dosing to the last drug administration of multiple dosing on D11 will be reviewed by the investigator and sponsor before the subsequent subjects in that dose cohort are enrolled. Subsequent subjects could be simultaneously enrolled, with one randomized to receive placebo and others randomized to receive PL-18.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A subject will be eligible for inclusion in this study only if all of the following criteria are met:
- •Voluntarily signed written informed consent;
- •Ability to comprehend the purpose of the study; ability to co-operate with the investigator and comply with all study requirements;
- •Adult females aged between 18 and 55 years (inclusive);
- •Body weight between 50 and 100 kg (inclusive) and body mass index (BMI) within 18\~32 kg/m2 (inclusive).
- •In good health as determined by screening tests. Good health is defined as having no clinically relevant abnormalities identified by a detailed medical history, full physical examination (including measurement of blood pressure and pulse rate), 12-lead ECG, and clinical laboratory tests:
- •Vital signs (measured after resting for 5 minutes seated position) within normal range, or outside the normal range and not considered clinically significant by the Investigator;
- •Standard 12-lead ECG parameters (recorded after resting for 5 minutes in supine position) in the following ranges; QTc (Fridericia algorithm recommended) ≤470 ms, and normal ECG tracing, or abnormal ECG tracing not considered clinically relevant by the Investigator;
- •Laboratory parameters demonstrating no clinically significant abnormalities, as determined by the Investigator. A total bilirubin outside the normal range may be acceptable if total bilirubin does not exceed 1.5 × ULN conjugated bilirubin (with the exception of a participant with documented Gilbert syndrome).
- •Self-report regular menstrual cycle (21-35 days), and planned to avoid menstruation from the first administration until 7 days after the last administration;
Exclusion Criteria
- •A subject meeting any of the following exclusion criteria will not be allowed to participate in this study:
- •Significant deep epithelial disruption by colposcopy at screening;
- •Anatomical anomalies of the genito-urinary tract and vaginal prolapse;
- •Genitourinary infections at screening or within 21 days prior to screening, including but not limited to bacterial urinary tract infection, bacterial vaginosis, trichomoniasis and vulvovaginal candidiasis;
- •Known, active sexually transmitted infection (STI) in partner, as per anamnesis;
- •Two or more confirmed trichomoniasis, gonococcal, chlamydia trachomatis or syphilis spirochete infections within 180 days prior to screening;
- •History of recurrent genital herpes or active herpes simplex virus (HSV) at screening;
- •Hepatitis B virus, hepatitis C virus, human immunodeficiency virus (HIV), syphilis infection, or positive hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C virus antibody (HCVAb), HIV antibody (HIVAb), treponema pallidum antibody (TP-Ab) at screening;
- •History of clinically severe relevant cardiovascular, hepatic, renal, pulmonary, gastrointestinal, endocrine, or neurological diseases that, in the investigator's opinion, may interfere with the aim of the study or affect the subject's safety;
- •Uncontrolled or acute illness that may complicate the study evaluation in the investigator's opinion;
Arms & Interventions
Antimicrobial Peptide PL-18 Vaginal Suppositories
Dose 1 to 5 of Antimicrobial Peptide PL-18 Vaginal Suppositories
Intervention: Dose 1 to 5 of Antimicrobial Peptide PL-18 Vaginal Suppositories
Placebo dose
Placebo dose 1 to 5 of Antimicrobial Peptide PL-18 Vaginal Suppositories
Intervention: Placebo dose 1 to 5 of Antimicrobial Peptide PL-18 Vaginal Suppositories
Outcomes
Primary Outcomes
Characterize safety profile of Antimicrobial Peptide PL-18 Vaginal Suppositories about the incidence of treatment emergent adverse events
Time Frame: 38 days
All AEs will be summarized by system organ class (SOC) and preferred term (PT). The numbers and percentages of subjects experiencing AEs will be calculated.
The numbers and percentages of subjects experiencing vital sign abnormalities with/without clinical significance.
Time Frame: 17 days
Vital signs abnormalities will be summarized with descriptive statistics. Vital signs include body temperature, blood pressure, heart rate/pulse, respiration. Changes from the baseline of each test over time will be summarized.
The numbers and percentages of subjects experiencing physical examination abnormalities with/without clinical significance.
Time Frame: Day 4 , Day 11 , Day 17
Physical examinations abnormalities will be summarized with descriptive statistics. Physical examination will include general condition, skin, head, eyes, ears, nose, throat, heart, lungs, chests, abdomen, extremities, nerves, back/spine, lymph, nodes. Changes from the baseline of each test over time will be summarized.
Safety assessment about the changes of clinical laboratory tests.
Time Frame: Day2, Day 4 , Day5, Day 8, Day 11 , Day 17
Laboratory abnormalities will be summarized with descriptive statistics. Clinical laboratory tests include hematology, blood chemistry, level of immune factors, urinalysis.
Safety assessment about the changes of 12-lead ECG .
Time Frame: Day1, Day 4 , Day 5, Day 7, Day 11 , Day 17
12-lead ECG abnormalities will be summarized with descriptive statistics.
Secondary Outcomes
- Maximum plasma concentration (Cmax)(Day1~Day4)
- Time to Maximum plasma concentration (Tmax)(Day1~Day4)
- Area under the concentration-time curve from the time zero to last measurable concentration (AUC0-t)(Day1~Day4)
- Area under concentration-time from time zero to infinity (AUC0-inf)(Day1~Day4)
- Terminal half-life (t1/2)(Day1~Day4)
- Apparent clearance (CL/F)(Day1~Day4)
- Apparent volume of distribution (Vz/F)(Day1~Day4)
- Mean residence time (MRT)(Day1~Day4)
- Terminal elimination rate constant (λz)(Day1~Day4)
- Maximum observed concentration at steady state (Cmax,ss)(Day5~Day 11)
- Minimum observed concentration at steady state (Cmin,ss)(Day5~Day 11)
- The average concentration during a dosing interval at steady state (Cav,ss)(Day5~Day 11)
- Area under the concentration-time curve from zero to the end of the dosing interval at steady state (AUCss)(Day5~Day 11)
- Accumulation ratio (Rac)(Day5~Day 11)
- Characterize the effect of Antimicrobial peptide PL-18 Vaginal Suppositories on vaginal bacteria(17 days)