Characterization of Doxycycline Pharmacokinetics and Adherence

Doxycycline is a Food and Drug Administration (FDA) approved broad-spectrum, second-generation tetracycline antibiotic that is generally well-tolerated and has been widely used as primary prophylaxis for bacterial and parasitic infections. While the pharmacokinetics (PK) of doxycycline in blood are well-described, knowledge gaps exist with intermittent dosing and establishing adherence thresholds for prophylactic use. Further, the multi-compartment distribution of the doxycycline has not been extensively characterized. The purpose of this study will be to characterize pharmacologic parameters for daily and non-daily doxycycline use and establish adherence cutoffs for daily and non-daily use.

Inclusion criteria

• Aged 18 to 65 years of age at the time of screening
• Able and willing to follow study participation requirements and provide informed consent to take part in the study
• Has a non-reactive/negative HIV test results at screening per applicable algorithm
• Has and is able to maintain a caput (head) of hair, that has not been chemically treated (defined as hair that has been bleached, permed, relaxed or dyed/colored) and is greater than one centimeter in length for the duration of the study
• For females of reproductive potential: Has a negative urine pregnancy test at screening
• For females of reproductive potential: Using at least two effective methods of contraception for at least 30 days (inclusive) prior to enrollment and intending to use two effective methods of contraception for the duration of study participation. It is strongly recommended that at least one barrier method (e.g. condoms) in addition to a hormonal contraception method be used. Examples of acceptable and effective methods include:

• Hormonal methods (oral pills, vaginal ring, depo, transdermal or implant)
• Intrauterine device (IUD) inserted at least 30 days prior to enrollment
• Surgical sterilization (of participant or partner(s)) including bilateral tubal ligation or vasectomized male partners
• Barrier methods (condom with/without spermicide, sponge, cervical cap, diaphragm)
• Self-identifies as having same sex partners
• Self-reported sexually abstinent as defined by abstaining from penile-vaginal intercourse for 90 days prior to enrollment and intending to remain sexually abstinent for the duration of study participation
• Has access to a smartphone and/or laptop and is able and willing to participate in video-based communications with study staff for directly observed dosing requirements
• In good general health, in the opinion of the investigator of record (IoR) or designee and has no medical condition that would adversely impact the conduct of the study (inclusive of self-reported conditions and/or those found upon medical history and examination or in available medical records). This includes, but is not limited to, having an intact, healthy gastrointestinal tract (without damage or functional disruption) and the ability to swallow pills

Exclusion criteria

• Per participant report, planned or active use of any anticonvulsants at screening and an unwillingness to restrict use of certain medications (iron, antacids, etc.) for the duration of the study
• For females of reproductive potential: Pregnant or currently breastfeeding, or intends to become pregnant and/or breastfeed during the study
• Has any of the following laboratory abnormalities:

• An estimated calculated creatinine clearance (CrCl) less than 60 mL/min by the Cockcroft-Gault formula at screening
• Positive for hepatitis B surface antigen (HBsAg) at screening
• Has a Grade 2 or higher clinically significant laboratory abnormality as defined by The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 - July 2017 (exception: a CrCl ≥ 60 mL/min at enrollment is permissible for enrollment)
• Per participant reported symptoms or clinical and/or laboratory diagnosis of an active pharyngeal, anorectal, or reproductive tract infection (RTI) requiring treatment at screening and enrollment per current US Centers for Disease Control and Prevention (CDC) guidelines (https://www.cdc.gov/std/treatment-guidelines/default.htm). Infections requiring treatment include Neisseria gonorrhoeae (GC), Chlamydia trachomatis (CT), syphilis, active herpes simplex virus (HSV) lesions, or symptomatic genital warts, chancroid, pelvic inflammatory disease (PID), bacterial vaginosis (BV), symptomatic vaginal candidiasis, and trichomoniasis
• Participation in research studies involving drugs, products, or vaccines within 30 days of the enrollment and for the duration of the study
• Has donated blood within 8 weeks of enrollment of approximately 1 pint (550 mL)
• Has a known allergy (adverse reaction) to any of the components of the study product, including known hypersensitivity to tetracycline-class antibiotics
• Prior use of doxycycline or any other tetracycline-class antibiotic within 30 days prior to enrollment
• Has an active infection that may be responsive to treatment with doxycycline or another tetracycline antibiotic
• Has evidence or history of any other condition (e.g., gastrectomy, seizure disorder), that, in the opinion of the IoR or designee, would make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives