Safety and Pharmacokinetic Study of Oral Maraviroc and Maraviroc 1% Gel in HIV-1 Seronegative Adults

Exclusion Criteria

• •1. Undergoing or completed gender reassignment
• •2. Participant reports any of the following at Screening:
• •1. Post-exposure prophylaxis for HIV exposure within 4 weeks prior to screening
• •2. Reports history of unprotected insertive or receptive anal intercourse within 3 months prior to screening
• •3. History of sexually transmitted disease in the last 3 months
• •4. Known HIV-infected partners
• •5. Non-therapeutic injection drug use in the 12 months prior to screening
• •6. History of recurrent urticaria
• •7. Allergy to soy, soybeans, peanuts, methylparaben, propylparaben, or sorbic acid
• •8. Use of antiretroviral medications with activity against HIV within the 4 weeks prior to the Enrollment
• •9. Use of systemic immunomodulatory medications within the 4 weeks prior to the Enrollment
• •10. Use of vaginally or rectally administered medications or products (including condoms) containing Nonoxynol-9 (N-9) within the 4 weeks prior to the Enrollment
• •11. Participating in another research study involving drugs or medical devices within the 4 weeks prior to the Enrollment
• •12. Has plans to relocate away from the study site area during the period of study participation
• •3. 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® (enoxaparin sodium)
• •2. Warfarin
• •3. Plavix® (clopidogrel bisulfate)
• •4. Any other drugs that are associated with increased likelihood of bleeding following mucosal biopsy (e.g., daily high dose aspirin (\> than 81 mg), NSAIDs, or Pradaxa®)
• •5. Rectally or vaginally administered medications (including over-the-counter products)
• •6. Use of potent CYP3A inhibitors (e.g., ketoconazole and clarithromycin), and CYP3A inducers (e.g., anti-convulsants and St.John's wort)
• •7. Multiple dose dexamethasone
• •8. Antiretroviral medications with activity against HIV
• •4. History of significant gastrointestinal bleeding in the opinion of the investigator
• •5. Abnormalities of the cervical, vaginal, or colorectal mucosa, or significant symptom(s), which in the opinion of the clinician represents a contraindication to protocol-required biopsies (including but not limited to presence of any unresolved injury, infectious or inflammatory condition of the local mucosa, and presence of symptomatic external hemorrhoids).
• •6. Body mass index (BMI) \< 18 or \> 35 kg/m2
• •7. 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 genital GC/CT identified at screening, one re-screening 2 months after screening visit will be allowed
• •8. Has any of the following laboratory abnormalities at Screening:
• •CHARM-03, Version 1.0 28 31st July 2014
• •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. Calculated creatinine clearance ≤ 70 mL/minute using the Cockcroft-Gault equation
• •5. Alanine transaminase (ALT) and/or aspartate aminotransferase (AST) \> 2.5× the site laboratory ULN
• •6. Total bilirubin \> 2.5 ULN
• •7. ≥ +1 glucose or +2 protein on urinalysis (UA)
• •8. International Normalized Ratio (INR) test \> 1.5× the site laboratory upper limit of normal (ULN)
• •9. Positive for Hepatitis B surface antigen (HBsAg)
• •10. Positive for Hepatitis C antibody (HCV Ab)
• •11. CCR5 Δ 32 homozygous or heterozygous
• •9. 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:
• •10. Participant reports any of the following at Screening:
• •1. Last pregnancy outcome or gynecological surgery 90 days or less prior to screening
• •2. Intends to become pregnant during the period of study participation
• •3. Chronic and/or recurrent symptomatic vaginal candidiasis