A Randomized, double-blind, placebo-controlled, single-dose, dose escalation study in healthy participants to evaluate safety, tolerability and pharmacokinetics of intra-vaginal ABI-1968
Clinical Network Services, Pty Ltd.
40 participants
Mar 23, 2017
Interventional
Conditions
Summary
This research study is testing the safety, tolerability and pharmacokinetics (looking at the amount of drug in your blood to evaluate the way the body processes the drug) of ABI-1968 Topical cream delivered to the cervix by intra-vaginal application. In this study, a total of 40 participants will be enrolled over 5 dosing groups/cohorts with each cohort consisting of 8 people – 6 will receive the active drug, and 2 will get placebo. Participants will be randomly assigned to receive either the active drug or placebo (a ‘dummy’ topical cream that looks identical, but contains no active drug). Participants will have a 75% chance of receiving study drug and 25% chance of receiving placebo. The study drug (or placebo) will be administered as a topical cream to the cervix by intra-vaginal application by the Gynecologist. No participant will be a member of more than one cohort. This study is a dose escalation study meaning that the first cohort will receive the lowest dose of study drug. The dose of study drug will increase with each subsequent cohort. Results will be reviewed by a safety monitoring committee after each dose strength has been tested to make sure that it is safe to continue with testing in the next cohort. The next cohort will not be enrolled until the safety monitoring committee have confirmed it is safe to do so. The study can be stopped at any time, based on evaluation of the side effects of the study drug. The five different dose strengths planned for this study are 0.01, 0.03, 0.1, 0.3 and 1.0 % by weight, applied as a topical cream via a single-use graduated applicator which delivers an approximate 2g dose. During this study, it is possible that the strengths may be reduced, repeated or increased; however, 1.0 % is the highest dose that will be given. Participants will not have a choice as to which cohort or dose level they are assigned (randomised) to, with each cohort enrolled on a first eligible basis. The participant and the study staff will not know if the they are assigned to receive the active study drug or the placebo, although in an emergency the study staff can find out. The first cohort will have 2 ‘sentinel’ volunteers; one will receive the active drug, the other the placebo. These individuals will receive the study drug (or placebo) approximately 24 hours before the rest of the cohort. Participants will be told if they are assigned to the sentinel cohort.
Eligibility
Inclusion Criteria10
- Women, 18 to 50 years old, with an intact uterus.
- Generally, in good health with no clinically significant pulmonary, cardiac, gastro-enterologic, neurologic, renal, musculoskeletal, rheumatologic, metabolic, neoplastic, or endocrine disease.
- Able and willing to use stringent methods of contraception after required abstinence period (up to Day 7) through to Day 28, including the use of a non-latex condom (for partner protection) and a second acceptable contraception method such as a vasectomy, contraceptive pill or IUDs are allowed. IUDs should be inserted at least 3 months prior to enrolment. The use of contraception methods such as a diaphragm, cervical caps, or Nuvaring - Registered Trademark, will not be allowed.
- Agree to provide coital history at study visits, and any local adverse reactions for sexual partner.
- Expect to have same sexual partner for duration of the study.
- Agree to abstain from activities such as sexual intercourse, vaginal douching or insertion of any vaginal products other than the study drug for at least 48 hours prior to enrolment through 7 days after dosing.
- Generally regular menstrual cycles.
- Able and willing to return to the clinic for all study procedures.
- Able and willing to provide informed consent.
- Negative Pap test at screening or within 3 months of enrolment, and no history of cervical intraepithelial lesions at any time.
Exclusion Criteria14
- Women who are pregnant, plan to become pregnant in the next 3 months, or lactating females.
- History of cancer, except basal cell or squamous cell carcinoma of the skin.
- History of genital herpes with >3 outbreaks per year, or active non-HPV vaginal infection.
- Have an active pelvic infection (positive urine screen for gonorrhea or chlamydial infection, positive bedside testing criteria for bacterial vaginosis, candida vaginitis or trichomonal vaginitis, positive bimanual exam consistent with pelvic inflammatory disease).
- Current or recent abnormal vaginal discharge and /or abnormal vaginal bleeding, within the 3 months prior to randomization.
- Had an abortion or miscarriage within the 3 months prior to randomization.
- Any clinically significant immune suppressing condition.
- Subjects with a significant acute condition or any other condition that in the opinion of the Investigator might interfere with the evaluation of the study objectives.
- Currently taking any of the following medications: inhaled or oral corticosteroids, immunomodulatory treatments, over the counter (OTC) intra-vaginal preparation, or any prescription that in the opinion of the Investigator could interfere with the interpretation of the results, within 2 weeks of enrolment.
- Hypersensitivity to any component of the placebo formulation excipients or other nucleoside analogues (such as cidofovir, etc.).
- Participation in any clinical study with an experimental medication or device within 30 days or 5 half-lives (whichever is longer) of enrolment.
- Menses expected to start within 7 days of enrolment.
- Current alcohol or substance abuse as assessed by the Principal Investigator.
- An employee, or family member of an employee, of the Sponsor, the CRO, or the Clinical Research Unit (CRU).
Interested in this trial?
Get notified about updates and connect with the research team.
Interventions
Phase 1 study in healthy female volunteers involving 5 Cohorts ABI-1968 Single dose topical cream delivered topically to the cervix by intra-vaginal application via a single-use graduated applicator which delivers an approximate 2g dose. Cohort 1: 0.01%, Cohort 2: 0.03%, Cohort 3: 0.1%, Cohort 4: 0.3%, Cohort 5: 1.0% - by weight The study drug (or placebo) will be administered as a topical cream to the cervix by intra-vaginal application by the Gynecologist. This study is a dose escalation study meaning that the first cohort will receive the lowest dose of study drug. The dose of study drug will increase with each subsequent cohort. Results will be reviewed by a safety monitoring committee after each dose strength has been tested to make sure that it is safe to continue with testing in the next cohort. The next cohort will not be enrolled until the safety monitoring committee have confirmed it is safe to do so. The study can be stopped at any time, based on evaluation of the side effects of the study drug. During this study, it is possible that the strengths may be reduced, repeated or increased; however, 1.0 % is the highest dose that will be given. Participants will not have a choice as to which cohort or dose level they are assigned (randomised) to, with each cohort enrolled on a rst eligible basis. The participant and the study sta will not know if the they are assigned to receive the active study drug or the placebo, although in an emergency the study staff can find out. The first cohort will have 2 ‘sentinel’ volunteers; one will receive the active drug, the other the placebo. These individuals will receive the study drug (or placebo) approximately 24 hours before the rest of the cohort. Participants will be told if they are assigned to the sentinel cohort.
Locations(1)
View Full Details on ANZCTR
For the most up-to-date information, visit the official listing.
ACTRN12617000467336