Human Immunodeficiency Virus (HIV) Prophylaxis Clinical Trial
Official title:
Open-Label Safety and Pharmacokinetic Study of Single (TDF), Dual (TDF-FTC), and Triple ARV IVR (TDF-FTC-MVC) in Healthy Women
| Verified date | June 2019 |
| Source | Auritec Pharmaceuticals |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This study will evaluate the hypothesis that intravaginal rings (IVRs) can safely and in a
sustained fashion, deliver the antiretroviral (ARV) drugs - tenofovir disoproxil fumarate
(TDF), emtricitabine (FTC), and maraviroc (MVC), in healthy women when used in the following
drug combinations: 1) TDF ("Single" IVR); 2) TDF-FTC ("Dual" IVR) and; 3) TDF-FTC-MVC
("Triple" IVR).
TDF = tenofovir disoproxil fumarate; FTC = emtrcitabine; MVC = maraviroc
| Status | Completed |
| Enrollment | 10 |
| Est. completion date | December 2016 |
| Est. primary completion date | December 2016 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Female |
| Age group | 18 Years to 45 Years |
| Eligibility |
Inclusion Criteria: - Provides written informed consent - Healthy female 18-45 years of age - HIV negative per subject report and results of screening examination - Negative for sexually transmitted diseases in the past 3 months and at screening exam - No history of genital herpes simplex I or II per subject report - Currently using contraception with plans to continue throughout the study duration or having sex with females only - Pre-menopausal with a regular menstrual cycle with at least 21 days between menses and no history of intermenstrual bleeding or with suppressed menstrual cycle by hormonal contraception such as Depo-Provera or continuous oral contraceptive agents - Subjects must agree to abstain from vaginal, anal, and oral sex throughout the first week of each dosing period and then use condoms for vaginal/rectal intercourse until after the final visit for use of each IVR - Subjects must agree to not douche or use any vaginal product other than the Single, Dual and Triple ARV IVRs, including lubricants, feminine hygiene products, and vaginal drying agents throughout the dosing period and until after the final visit - Subjects must agree to blood draws and vaginal exams throughout the course of the study Exclusion Criteria: - HIV positive by subject report or results of screening examination - Positive history for autoimmune disease - Abnormal genital exam defined as grade 1 or higher adverse event by DAIDS genital AE grading table - Abnormal ALT or AST or Hepatitis B infection - Active vaginal infection as determined by site IoR - Abnormal renal function (defined as a creatinine clearance of <50mL/min/1.73 m2) - Pregnant or less than 6 months post-partum or current lactation - Current use of an IVR (i.e., Nuvaring, Estring, Femring) - History of TDF, FTC, and MVC use and/or adverse reaction to any of these drugs - History of adverse reaction to silicone - History of toxic shock syndrome - Currently receiving chemotherapy or immunosuppressive agents - Use of investigative drugs within 30 days or 5 half-lives - Currently using or suspected to be using non-therapeutic injection drugs |
| Country | Name | City | State |
|---|---|---|---|
| United States | University of Texas Medical Branch | Galveston | Texas |
| Lead Sponsor | Collaborator |
|---|---|
| Auritec Pharmaceuticals | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Oak Crest Institute of Science, The University of Texas Medical Branch, Galveston |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) | Number of Adverse Events (AEs) was recorded. Safety parameters were monitored for each IVR combination and the grading scale for each parameter followed the Female Genital Grading Table for Use in Microbicide Studies. AEs not included in that table were graded using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014 (Grade 1 = mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Potentially Life-Threatening). | Days 0-21 following insertion of each IVR. | |
| Primary | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Fluid (CVF) | Drug concentrations [tenofovir (TFV), tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and maraviroc (MVC)] in cervicovaginal fluids (CVF) for each IVR combination. | Time points at which outcome measure was assessed are Days 2 (after IVR insertion) and 7 (day of IVR removal). | |
| Primary | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Lavage (CVL) | Drug concentrations [tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and maraviroc (MVC)] in cervicovaginal lavage (CVL) were evaluated for each IVR combination. | Time points at which outcome measure was assessed are Days 2 (after IVR insertion) and 7 (day of IVR removal). | |
| Primary | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Vaginal Tissue | Drug concentrations [tenofovir disoproxil fumarate (TDF), tenofovir (TFV), tenofovir diphosphate (TFV-DP), emtricitabine (FTC) and maraviroc (MVC)] in vaginal tissue (VT) were evaluated for each IVR combination. | Time points at which outcome measure was assessed are Days 2 (after IVR insertion) and 7 (day of IVR removal). | |
| Primary | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Plasma | Drug concentrations [tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and maraviroc (MVC)] in plasma were evaluated for each IVR combination. | Time points at which outcome measure was assessed are Days 2 (after IVR insertion) and 7 (day of IVR removal). | |
| Primary | Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Terminal Half-life | Drug concentrations [tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and maraviroc (MVC)] in terminal half-life were evaluated for each IVR combination. | Time points at which outcome measure was assessed are Day 7 (day of IVR removal) and daily up to 14 days. | |
| Secondary | Acceptability of the IVRs | Acceptability of the IVRs was assessed through reported willingness to use the IVR for 28 days in a real-world setting on a likert scale, 1 being "not at all confident" to 5 being "completely confident" for Periods 1 and 2. | Days 0-21 following insertion of each IVR. |