HIV
Conditions
Brief summary
A double-blind, randomised, placebo-controlled, dose escalation trial to evaluate the safety and to assess local and systemic pharmacokinetics of ds003 vaginal tablets administered to healthy HIV-negative women.
Interventions
DRUGDS003 vaginal tablet
The trial will be conducted in three cohorts of 12 women each. In each cohort, participants will be randomised in a 3:1 ratio to receive either DS003 or placebo on Day 0 and Day 17. In each cohort, therefore, 9 participants will receive DS003 vaginal tablets and 3 participants will receive placebo vaginal tablets.
DRUGPlacebo
Sponsors
International Partnership for Microbicides, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Women must meet all of the following criteria to be eligible for enrolment: 1. Women ≥ 18 and ≤ 45 years of age who can give written informed consent 2. BMI of ≥ 18 and \< 30 kg/m2 3. Vital signs within normal limits and no clinically significant ECG findings 4. Available for all visits and consent to follow all procedures scheduled for the trial 5. Healthy, based on medical history, vital signs, physical examination, urinalysis (dipstick and microscopy), laboratory evaluations for genital infections (bacterial vaginosis, gonorrhoea, chlamydia and trichomonas) and laboratory evaluations for haematology and biochemistry 6. HIV-negative as determined by an HIV test at the time of screening 7. On a stable form of contraception, defined as: * A stable oral contraceptive regimen for at least 2 months prior to enrolment, OR * Transdermal contraceptive patch for at least 3 months prior to enrolment, OR * Subcutaneous implant inserted at least 3 months prior to enrolment, OR * Long-acting progestins for at least 2 consecutive injections, OR An IUD inserted (with no vaginal or gynaecological complaints associated with its use) at least 3 months prior to enrolment, OR * Have undergone surgical sterilisation at least 3 months prior to enrolment AND be willing to use oral contraceptives if necessary to delay menstruation while taking part in the trial 8. Upon pelvic examination and colposcopy at screening and visual inspection of the cervix at the time of enrolment, the cervix and vagina appear normal as determined by the Investigator 9. Asymptomatic for urogenital infections at the time of screening (if a woman is diagnosed with any curable STI, either clinically or by laboratory test at the time of screening, she must complete the full course of treatment and have a healthy genital tract before being considered for potential re-screening) 10. Willing to refrain from the use of topical vaginal medications, vaginal products or objects, including tampons, female condoms, cotton wool, rags, diaphragms, cervical caps (or any other vaginal barrier method), douches, lubricants, vibrators/dildos, and drying agents for 7 days prior to enrolment and for the duration of the trial 11. Documentation of no abnormality on cervical cytology, including grossly bloody smear, within 90 days prior to screening 12. Willing to refrain from participation in any other research trial for the duration of this trial 13. Willing to provide adequate locator information for trial retention purposes and be reachable per local standard procedures, e.g. by home visit or telephone, or via family or close neighbour contacts (confidentiality to be maintained) 14. Willing to agree to abstain from all the following for a total of 2 days (48 hours) prior to each trial visit, and for a total of 3 days (72 hours) after the biopsy procedure: Penile-vaginal intercourse • Oral contact with her genitalia 15. Hepatitis B and C negative at the time of screening
Exclusion criteria
Women who meet any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the safety of three escalating doses of DS003 (1 mg, 3 mg and 10 mg), administered in a vaginal tablet formulation, to healthy, HIV-negative female volunteers. | 12 weeks | Gynaecological assessments, including pelvic examination and colposcopy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the local (vaginal fluids) and systemic (plasma) DS003 PK profile and the 24 hour cervical tissue concentration when administered in three escalating doses of a vaginal tablet formulation. | 12 weeks | Measurement of DS003 concentrations in plasma, vaginal fluids and cervical tissue collected at various time points after administration of the vaginal tablet(s). |
Outcome results
None listed