Clinical trial NCT01575405 (phase 1, status: completed)
Conditions: hiv prevention
ICD codes: B20, Z71.7, O98.72, Z21, O98.73, R75, Z11.4
Drugs: rectal formulation (rf) of tenofovir 1% gel, vaginal formulations (original vf and reduced vaginal glycerin formulation rgvf) of tenofovir 1% gel, universal hec placebo gel formulation
SMILES: C[C@H](CN1C=NC2=C1N=CN=C2N)OCP(O)(O)=O, OCC(O)CO, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          1. ≥ Age of 18 at screening

          2. Willing and able to communicate in English

          3. Willing and able to provide written informed consent to take part in the study

          4. Willing and able to provide adequate locator information

          5. Understands and agrees to local sexually transmitted infection (STI) reporting
             requirements

          6. HIV-1 uninfected at screening according to the standard DAIDS algorithm in Appendix II

          7. Must have been vaccinated for or have natural immunity to Hepatitis B, which will be
             verified by a positive Hepatitis B surface antibody (HBsAb) test at screening (Note:
             One re-screen will be allowed for individuals who are non immune to Hepatitis B but
             undergo vaccination.)

          8. Availability to return for all study visits, barring unforeseen circumstances

          9. Willing to abstain from RAI and practices involving insertion of anything in rectum
             (drug, enema, penis, or sex toy) for 72 hours before and 72 hours after each flexible
             sigmoidoscopy and study product exposure.

         10. Must agree to use study provided condoms for the duration of the study

         11. Must be in general good health

         12. Must agree not to participate in other concurrent interventional and/or drug trials

         13. Per participant report at screening, a history of consensual RAI at least once in the
             last three months.

             In addition to the criteria listed above, female participants must meet the following
             criteria:

         14. Willing to abstain from insertion of anything into vagina (drug, douche, penis, or sex
             toy) other than the swabs/sponges for study related specimen collection for 24 hours
             before and after each study product exposure

         15. Post-menopausal or using (or willing to use) an acceptable form of contraception
             (e.g., intrauterine device (IUD), hormonal contraception, surgical sterilization, or
             vasectomization of male partner). If the female participant has female partners only,
             the method of contraception will be noted as a barrier method in the study
             documentation. Temporary abstinence due to absence of partner(s) for the duration of
             the study will be acceptable.

        Exclusion Criteria:

          1. Abnormalities of the colorectal mucosa, or significant colorectal symptom(s), which in
             the opinion of the clinician represents a contraindication to biopsy (including but
             not limited to presence of any unresolved injury, infectious or inflammatory condition
             of the local mucosa, and presence of symptomatic external hemorrhoids).

          2. At screening: participant-reported symptoms and/or clinical or laboratory diagnosis of
             active rectal or reproductive tract infection requiring treatment per current CDC
             guidelines or symptomatic urinary tract infection (UTI). Infections requiring
             treatment include symptomatic bacterial vaginosis, symptomatic vaginal candidiasis,
             other vaginitis, trichomoniasis, Chlamydia (CT), gonorrhea (GC), syphilis, active HSV
             lesions, chancroid, pelvic inflammatory disease, genital sores or ulcers, cervicitis,
             or symptomatic genital warts requiring treatment. Note that an HSV-1 or HSV-2
             seropositive diagnosis with no active lesions is allowed, since treatment is not
             required. (Note: In cases of non-anorectal GC/CT identified at screening, one
             re-screening 2 months after screening visit will be allowed.)

          3. Per participant report and/or clinical or laboratory diagnosis, anorectal STI within
             six months prior to the Screening Visit

          4. At screening:

               1. Hemoglobin < 10.0 g/dL

               2. Platelet count less than 100,000/mm3

               3. White blood cell count < 2,000 cells/mm3 or > 15,000 cells/mm3

               4. For females: calculated creatinine clearance less than 60 mL/min by the
                  Cockcroft-Gault formula where creatinine clearance in mL/min (140- age in years)
                  x (weight in kg) x (0.85 for female)/72 x (serum creatinine in mg/dL)

               5. For males: calculated creatinine clearance less than 60 mL/min by the
                  Cockcroft-Gault formula where creatinine clearance in mL/min = (140 - age in
                  years) x (weight in kg) x (1 for male)/72 x (serum creatinine in mg/dL)

               6. Serum creatinine > 1.3× the site laboratory upper limit of normal (ULN)

               7. Alanine transaminase (ALT) and/or aspartate aminotransferase (AST) > 2.5× the
                  site laboratory ULN

               8. +1 glucose or +1 protein on urinalysis (UA)

               9. History of bleeding problems (verified via prothrombin time (PT)/ International
                  Normalized Ratio (INR) test)

              10. Positive for Hepatitis B surface antigen (HBsAg)

          5. History of significant gastrointestinal bleeding in the opinion of the investigator

          6. Known allergic reaction to methylparaben, propylparaben, sorbic acid, glycerin,
             glycerol, or tenofovir

          7. Current known HIV-infected partner(s)

          8. By participant report at enrollment, history of excessive daily alcohol use (as
             defined by the CDC as heavy drinking consisting of an average consumption of more than
             2 drinks per day for men, and more than 1 drink per day for women), frequent binge
             drinking or illicit drug use that includes any injection drugs, methamphetamines
             (crystal meth), heroin, or cocaine including crack cocaine, within the past 12 months

          9. Per participant report at screening, anticipated use and/or unwillingness to abstain
             from the following medications during the period of study participation:

               1. Heparin, including Lovenox®

               2. Warfarin

               3. Plavix® (clopidogrel bisulfate)

               4. Rectally administered medications (including over-the-counter products)

               5. Acyclovir, valacyclovir, famciclovir, and TDF

               6. >81 mg of aspirin per day AND unwillingness and/or inability to completely stop
                  all use of aspirin or aspirin-containing medications for 3 days before and 3 days
                  after the biopsy collection procedure

               7. Non-steroidal anti-inflammatory drugs (NSAIDS)

               8. Any other drugs that are associated with increased likelihood of bleeding
                  following mucosal biopsy

         10. By participant report at screening, use of systemic immunomodulatory medications,
             rectally administered medications, rectally administered products (including condoms)
             containing N-9, or any investigational products within the 4 weeks prior to the
             Enrollment/Baseline Evaluation Visit and throughout study participation

         11. History of recurrent urticaria

         12. Any other condition or prior therapy that, in the opinion of the investigator, would
             preclude informed consent, make study participation unsafe, make the individual
             unsuitable for the study or unable to comply with the study requirements. Such
             conditions may include, but are not limited to, current or recent history of severe,
             progressive, or uncontrolled substance abuse, or renal, hepatic, hematological,
             gastrointestinal, endocrine, pulmonary, neurological, or cerebral disease

             In addition to the criteria listed above, female participants will be excluded if they
             meet any of the following criteria:

         13. Pregnant at the Enrollment/Baseline Visit

         14. Breastfeeding at screening or intend to breastfeed during study participation per
             participant report.