Bacterial Vaginosis, Colpomycosis, Mixede Vaginitis
Conditions
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.
Interventions
DRUGDose 1 to 5 of Antimicrobial Peptide PL-18 Vaginal Suppositories
Escalating doses of 1 mg (0.1%)、2.5mg (0.25%)、5 mg (0.5%)、10mg (1%)、15 mg (1.5%)；single dose administration；topical vaginal suppository ；multiple-dose administration after single dose administration a 3-day wash out period ; once-daily for 6 consecutive days;
DRUGPlacebo dose 1 to 5 of Antimicrobial Peptide PL-18 Vaginal Suppositories
Dose 1、2、3、4 and 5 of Antimicrobial Peptide PL-18 Vaginal Suppositories respective placebos；single dose administration；topical vaginal suppository ；multiple-dose administration after single dose administration a 3-day wash out period ; once-daily for 6 consecutive days;
Sponsors
Protelight Pharmaceuticals Australia PTY LTD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* A subject will be eligible for inclusion in this study only if all of the following criteria are met: 1. Voluntarily signed written informed consent; 2. Ability to comprehend the purpose of the study; ability to co-operate with the investigator and comply with all study requirements; 3. Adult females aged between 18 and 55 years (inclusive); 4. Body weight between 50 and 100 kg (inclusive) and body mass index (BMI) within 18\ 32 kg/m2 (inclusive). 5. 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). 6. Self-report regular menstrual cycle (21-35 days), and planned to avoid menstruation from the first administration until 7 days after the last administration; 7. Negative human papilloma virus (HPV) test result (at screening or negative HPV test result performed in study site within 2 months prior to screening; 8. History of sexual life, including vaginal intercourse; 9. Be willing to use vaginal suppositories; 10. Currently in a mutually monogamous sexual relationship or no sexual activity; 11. Sexual abstinence from 72 hours prior to the first drug administration until 7 days after the last administration; 12. Agreement to avoid the use of any other intravaginal products (i.e., contraceptive creams, gels, foams, sponges, lubricants, irrigation solutions, etc.) from screening until 7 days after the last administration; 13. Subjects in a intercourse relationship must agree to use highly effective methods of contraception (as specified in Section 4.6.3) from informed consent obtained until 3 months after the last administration, and pregnancy test results must be negative at screening.
Exclusion criteria
* A subject meeting any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Characterize safety profile of Antimicrobial Peptide PL-18 Vaginal Suppositories about the incidence of treatment emergent adverse events | 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. | 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. | 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. | 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 . | Day1, Day 4 , Day 5, Day 7, Day 11 , Day 17 | 12-lead ECG abnormalities will be summarized with descriptive statistics. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent clearance (CL/F) | Day1~Day4 | CL/F is a PK parameter of the single-dose stage.Plasma PK parameters will be analyzed by non-compartmental analysis (NCA) with WinNonlin® version 8.1 or above and SAS® version 9.4 or higher. |
| Apparent volume of distribution (Vz/F) | Day1~Day4 | Vz/F is a PK parameter of the single-dose stage.Plasma PK parameters will be analyzed by non-compartmental analysis (NCA) with WinNonlin® version 8.1 or above and SAS® version 9.4 or higher. |
| Mean residence time (MRT) | Day1~Day4 | MRT is a PK parameter of the single-dose stage.Plasma PK parameters will be analyzed by non-compartmental analysis (NCA) with WinNonlin® version 8.1 or above and SAS® version 9.4 or higher. |
| Terminal elimination rate constant (λz) | Day1~Day4 | λz is a PK parameter of the single-dose stage.Plasma PK parameters will be analyzed by non-compartmental analysis (NCA) with WinNonlin® version 8.1 or above and SAS® version 9.4 or higher. |
| Maximum observed concentration at steady state (Cmax,ss) | Day5~Day 11 | Concentrations of Antimicrobial Peptide PL-18 in Plasma samples at different time points are measured.Maximum observed concentration at steady state (Cmax,ss) is a PK parameter of the multi-dose stage. |
| Maximum plasma concentration (Cmax) | Day1~Day4 | Concentrations of Antimicrobial Peptide PL-18 in Plasma samples at different time points are measured.Maximum plasma concentration (Cmax) is a PK parameter of the single-dose stage.Plasma concentrations at different time points will be listed and summarized by descriptive statistics. |
| The average concentration during a dosing interval at steady state (Cav,ss) | Day5~Day 11 | The average concentration during a dosing interval at steady state (Cav,ss) is a PK parameter of the multi-dose stage. Plasma PK parameters will be analyzed by non-compartmental analysis (NCA) with WinNonlin® version 8.1 or above and SAS® version 9.4 or higher. |
| Area under the concentration-time curve from zero to the end of the dosing interval at steady state (AUCss) | Day5~Day 11 | AUCss is a PK parameter of the multi-dose stage. Plasma PK parameters will be analyzed by non-compartmental analysis (NCA) with WinNonlin® version 8.1 or above and SAS® version 9.4 or higher. |
| Accumulation ratio (Rac) | Day5~Day 11 | Accumulation ratio (Rac) is a PK parameter of the multi-dose stage. Plasma PK parameters will be analyzed by non-compartmental analysis (NCA) with WinNonlin® version 8.1 or above and SAS® version 9.4 or higher. |
| Characterize the effect of Antimicrobial peptide PL-18 Vaginal Suppositories on vaginal bacteria | 17 days | Changes in vaginal bacteria after single and multiple doses of Antimicrobial Peptide PL-18 Vaginal Suppositories in healthy adult female subjects assessed. Changes in vaginal bacteria will be summarized with descriptive statistics. |
| Minimum observed concentration at steady state (Cmin,ss) | Day5~Day 11 | Concentrations of Antimicrobial Peptide PL-18 in Plasma samples at different time points are measured. Minimum observed concentration at steady state (Cmin,ss) is a PK parameter of the multi-dose stage. |
| Time to Maximum plasma concentration (Tmax) | Day1~Day4 | Tmax is a PK parameter of the single-dose stage.Plasma PK parameters will be analyzed by non-compartmental analysis (NCA) with WinNonlin® version 8.1 or above and SAS® version 9.4 or higher. |
| Area under the concentration-time curve from the time zero to last measurable concentration (AUC0-t) | Day1~Day4 | AUC0-t is a PK parameter of the single-dose stage.Plasma PK parameters will be analyzed by non-compartmental analysis (NCA) with WinNonlin® version 8.1 or above and SAS® version 9.4 or higher. |
| Area under concentration-time from time zero to infinity (AUC0-inf) | Day1~Day4 | AUC0-t is a PK parameter of the single-dose stage.Plasma PK parameters will be analyzed by non-compartmental analysis (NCA) with WinNonlin® version 8.1 or above and SAS® version 9.4 or higher. |
| Terminal half-life (t1/2) | Day1~Day4 | t1/2 is a PK parameter of the single-dose stage.Plasma PK parameters will be analyzed by non-compartmental analysis (NCA) with WinNonlin® version 8.1 or above and SAS® version 9.4 or higher. |
Countries
Australia
Contacts
Primary ContactKristi McLendon, Dr
Outcome results
None listed