Characterization of Doxycycline Pharmacokinetics and Adherence

Characterization of Doxycycline Pharmacokinetics and Adherence Post-Single and Repeat Dosing Schemas

The purpose of this study is to evaluate the effect of body changes on doxycycline concentrations for different dosing schedules. This study will involve a single dose phase and a multiple dose phase. Healthy individuals who do not have a sexually transmitted infection (STI), including acute (e.g., gonorrhea or chlamydia) or chronic (e.g., HIV or HSV-2) infections will be enrolled in this study. Study participants will be randomized to a dosing schedule in each phase and come to the research clinic throughout their time on study for sample collection. Study participants that choose to enroll in this study will be enrolled for about 37 days.

Study Overview

• Status: Enrolling by invitation
• Conditions: Sexually Transmitted Infection
• Intervention / Treatment: Drug: Single-Dose PK Phase - DR Group; Drug: Multi-Dose PK Phase - Daily Group; Drug: Single-Dose PK Phase - IR Group; Drug: Multi-Dose PK Phase - Intermittent Group

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Aged 18 to 65 years of age at the time of screening
2. Able and willing to follow study participation requirements and provide informed consent to take part in the study
3. Has a non-reactive/negative HIV test results at screening per applicable algorithm
4. 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
5. For females of reproductive potential: Has a negative urine pregnancy test at screening

6. 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:

   1. Hormonal methods (oral pills, vaginal ring, depo, transdermal or implant)
   2. Intrauterine device (IUD) inserted at least 30 days prior to enrollment
   3. Surgical sterilization (of participant or partner(s)) including bilateral tubal ligation or vasectomized male partners
   4. Barrier methods (condom with/without spermicide, sponge, cervical cap, diaphragm)
   5. Self-identifies as having same sex partners
   6. 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
7. 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
8. 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:

1. 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
2. For females of reproductive potential: Pregnant or currently breastfeeding, or intends to become pregnant and/or breastfeed during the study

3. Has any of the following laboratory abnormalities:

   1. An estimated calculated creatinine clearance (CrCl) less than 60 mL/min by the Cockcroft-Gault formula at screening
   2. Positive for hepatitis B surface antigen (HBsAg) at screening
   3. 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)
4. 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
5. Participation in research studies involving drugs, products, or vaccines within 30 days of the enrollment and for the duration of the study
6. Has donated blood within 8 weeks of enrollment of approximately 1 pint (550 mL)
7. Has a known allergy (adverse reaction) to any of the components of the study product, including known hypersensitivity to tetracycline-class antibiotics
8. Prior use of doxycycline or any other tetracycline-class antibiotic within 30 days prior to enrollment
9. Has an active infection that may be responsive to treatment with doxycycline or another tetracycline antibiotic
10. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single-Dose PK Phase- 200mg delayed release (DR) doxycycline tablet; Participants in this arm will take one 200 mg delayed release (DR) doxycycline hyclate tablet	Drug: Single-Dose PK Phase - DR Group; One 200 mg doxycycline hyclate delayed release (DR) tablet
Experimental: Multi-Dose PK Phase- daily dosing (every 24 hours); Participants randomized to this arm will receive one 200mg doxycycline hyclate delayed release (DR) tablet daily (every 24 hours) for 10 days.	Drug: Multi-Dose PK Phase - Daily Group; One 200 mg doxycycline hyclate delayed release (DR) tablet every 24 hours
Experimental: Single Dose PK Phase- Two 100mg immediate release (IR) doxycycline tablets; Participants in this arm will take two 100mg immediate release (IR) doxycycline hyclate tablets	Drug: Single-Dose PK Phase - IR Group; Two 100 mg doxycycline hyclate immediate-release (IR) tablets
Experimental: Multi-dose PK Phase- Intermittent (every 72 hours) dosing; Participants randomized to this arm will receive one 200mg doxycycline hyclate delayed release (DR) tablet intermittently (every 72 hours) for 10 days.	Drug: Multi-Dose PK Phase - Intermittent Group; One 200 mg doxycycline hyclate delayed release (DR) tablet every 72 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma concentration (Cmax) for 200mg doxycycline hyclate after a single dose.	Median (IQR) plasma doxycycline hyclate Cmax (ng/mL units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Minimum observed plasma concentration (Cmin) for 200mg doxycycline hyclate after a single dose.	Median (IQR) plasma doxycycline hyclate Cmin (ng/mL units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Time to reach maximum plasma concentration (Tmax) of 200mg doxycycline hyclate after a single dose.	Median (IQR) plasma doxycycline hyclate Tmax (hours units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Plasma half-life (T1/2) of 200mg doxycycline hyclate after a single dose.	Median (IQR) plasma doxycycline hyclate half-life (T1/2, hours units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Area Under the Concentration-Time Curve in plasma From One to 336 Hours After Dosing (AUC0-24) of 200mg doxycycline hyclate.	Median (IQR) plasma doxycycline hyclate area under the concentration time curve (AUC)0-inf (ng*hr/mL units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Plasma concentrations at 24 hours (C24) post last dose of doxycycline following 10 days of daily or intermittent dosing.	Median (IQR) plasma concentration at 24 hours post last dose (ng/mL units)	24 hours post last dose of the multiple dose phase.
Plasma concentrations at 48 hours (C48) post last dose of doxycycline following 10 days of daily or intermittent dosing.	Median (IQR) plasma concentration at 48 hours post last dose (ng/mL units)	48 hours post last dose of the multiple dose phase.
Plasma concentrations at 72 hours (C72) post last dose of doxycycline following 10 days of daily or intermittent dosing.	Median (IQR) plasma concentration at 72 hours post last dose (ng/mL units)	72 hours post last doseof the multiple dose phase.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of gastrointestinal (GI)-related adverse events reported after doxycycline hyclate dosing during the multiple dose phase.	Number of GI-related adverse events during 10 days of daily or intermittent doxycycline dosing	Study visit days 14-23
Number of gastrointestinal (GI)-related adverse events reported after doxycycline hyclate dosing after the multiple dose phase.	Number of GI-related adverse events for 14 days following final daily or intermittent dose (through the Final/Day 37 visit)	Up to 14 days post last dose.
Maximum observed dried blood spot (DBS) concentration (Cmax) for 200mg doxycycline hyclate after a single dose.	Median (IQR) DBS doxycycline hyclate Cmax (ng/mL units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Minimum observed dried blood spot (DBS) concentration (Cmin) for 200mg doxycycline hyclate after a single dose.	Median (IQR) DBS doxycycline hyclate Cmin (ng/mL units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Time to reach maximum dried blood spot (DBS) concentration (Tmax) of 200mg doxycycline hyclate after a single dose.	Median (IQR) DBS doxycycline hyclate Tmax (hours units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Dried blood spot (DBS) half-life (T1/2) of 200mg doxycycline hyclate after a single dose.	Median (IQR) DBS doxycycline hyclate half-life (T1/2, hours units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Area Under the Concentration-Time Curve in dried blood spots (DBS) From One to 336 Hours After Dosing (AUC0-24) of 200mg doxycycline hyclate.	Median (IQR) DBS doxycycline hyclate area under the concentration time curve (AUC)0-inf (ng*hr/mL units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Maximum observed anorectal fluid concentration (Cmax) for 200mg doxycycline hyclate after a single dose.	Median (IQR) anorectal doxycycline hyclate Cmax (ng/swab units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Minimum observed anorectal fluid concentration (Cmin) for 200mg doxycycline hyclate after a single dose.	Median (IQR) anorectal doxycycline hyclate Cmin (ng/swab units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Time to reach maximum anorectal fluid concentration (Tmax) of 200mg doxycycline hyclate after a single dose.	Median (IQR) anorectal doxycycline hyclate Tmax (hours units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Anorectal fluid half-life (T1/2) of 200mg doxycycline hyclate after a single dose.	Median (IQR) anorectal doxycycline hyclate half-life (T1/2, hours units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Area Under the Concentration-Time Curve in anorectal fluid From One to 336 Hours After Dosing (AUC0-24) of 200mg doxycycline hyclate.	Median (IQR) anorectal doxycycline hyclate area under the concentration time curve (AUC)0-inf (ng*hr/swab units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Maximum observed vaginal fluid concentration (Cmax) for 200mg doxycycline hyclate after a single dose.	Median (IQR) vaginal doxycycline hyclate Cmax (ng/swab units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Minimum observed vaginal fluid concentration (Cmin) for 200mg doxycycline hyclate after a single dose.	Median (IQR) vaginal doxycycline hyclate Cmin (ng/swab units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Time to reach maximum vaginal fluid concentration (Tmax) of 200mg doxycycline hyclate after a single dose.	Median (IQR) vaginal doxycycline hyclate Tmax (hours units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Vaginal fluid half-life (T1/2) of 200mg doxycycline hyclate after a single dose.	Median (IQR) vaginal doxycycline hyclate half-life (T1/2, hours units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Area Under the Concentration-Time Curve in vaginal fluid From One to 336 Hours After Dosing (AUC0-24) of 200mg doxycycline hyclate.	Median (IQR) vaginal doxycycline hyclate area under the concentration time curve (AUC)0-inf (ng*hr/swab units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Maximum observed pooled urine concentration (Cmax) for 200mg doxycycline hyclate after a single dose.	Mean (95% CI) urine doxycycline hyclate Cmax (ng/mL units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Minimum observed pooled urine concentration (Cmin) for 200mg doxycycline hyclate after a single dose.	Mean (95% CI) urine doxycycline hyclate Cmin (ng/mL units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Time to reach maximum pooled urine concentration (Tmax) of 200mg doxycycline hyclate after a single dose.	Mean (95% CI) urine doxycycline hyclate Tmax (hours units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Pooled urine half-life (T1/2) of 200mg doxycycline hyclate after a single dose.	Mean (95% CI) urine doxycycline hyclate half-life (T1/2, hours units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Area Under the Concentration-Time Curve in urine From One to 336 Hours After Dosing (AUC0-24) of 200mg doxycycline hyclate.	Mean (95% CI) urine doxycycline hyclate area under the concentration time curve (AUC)0-inf (ng*hr/mL units)	1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.
Dried blood spot (DBS) concentrations at 24 hours (C24) post last dose of doxycycline following 10 days of daily or intermittent dosing.	Median (IQR) DBS concentration at 24 hours post last dose (ng/mL units)	24 hours post last dose of the multiple dose phase.
Dried blood spot (DBS) concentrations at 48 hours (C48) post last dose of doxycycline following 10 days of daily or intermittent dosing.	Median (IQR) DBS concentration at 48 hours post last dose (ng/mL units)	48 hours post last dose of the multiple dose phase.
Dried blood spot (DBS) concentrations at 72 hours (C72) post last dose of doxycycline following 10 days of daily or intermittent dosing.	Median (IQR) DBS concentration at 72 hours post last dose (ng/mL units)	72 hours post last dose of the multiple dose phase.
Urine concentrations at 24 hours (C24) post last dose of doxycycline following 10 days of daily or intermittent dosing.	Median (IQR) urine concentration at 24 hours post last dose (ng/mL units)	24 hours post last dose of the multiple dose phase.
Urine concentrations at 48 hours (C48) post last dose of doxycycline following 10 days of daily or intermittent dosing.	Median (IQR) urine concentration at 48 hours post last dose (ng/mL units)	48 hours post last dose of the multiple dose phase.
Urine concentrations at 72 hours (C72) post last dose of doxycycline following 10 days of daily or intermittent dosing.	Median (IQR) urine concentration at 72 hours post last dose (ng/mL units)	72 hours post last dose of the multiple dose phase.
Anorectal fluid concentrations at 24 hours (C24) post last dose of doxycycline following 10 days of daily or intermittent dosing.	Median (IQR) anorectal concentration at 24 hours post last dose (ng/swab units)	24 hours post last dose of the multiple dose phase.
Anorectal fluid concentrations at 48 hours (C48) post last dose of doxycycline following 10 days of daily or intermittent dosing.	Median (IQR) anorectal concentration at 48 hours post last dose (ng/swab units)	48 hours post last dose of the multiple dose phase.
Anorectal fluid concentrations at 72 hours (C72) post last dose of doxycycline following 10 days of daily or intermittent dosing.	Median (IQR) anorectal concentration at 72 hours post last dose (ng/swab units)	72 hours post last dose of the multiple dose phase.
Vaginal fluid concentrations at 24 hours (C24) post last dose of doxycycline following 10 days of daily or intermittent dosing.	Median (IQR) vaginal concentration at 24 hours post last dose (ng/swab units)	24 hours post last dose of the multiple dose phase.
Vaginal fluid concentrations at 48 hours (C48) post last dose of doxycycline following 10 days of daily or intermittent dosing.	Median (IQR) vaginal concentration at 48 hours post last dose (ng/swab units)	48 hours post last dose of the multiple dose phase.
Vaginal fluid concentrations at 72 hours (C72) post last dose of doxycycline following 10 days of daily or intermittent dosing.	Median (IQR) vaginal concentration at 72 hours post last dose (ng/swab units)	72 hours post last dose of the multiple dose phase.

Collaborators and Investigators

• Sponsor: HIV Prevention Trials Network
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Mackenzie Cottrell, PharmD, MS, University of North Carolina, Chapel Hill; Study Chair: Mark Marzinke, PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: August 5, 2026
• First Submitted That Met QC Criteria: August 5, 2026
• First Posted (Actual): August 10, 2026

Study Record Updates

• Last Update Posted (Actual): September 17, 2026
• Last Update Submitted That Met QC Criteria: September 14, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Doxycycline; PK Sampling
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Pathological Conditions, Signs and Symptoms; Sexually Transmitted Diseases
• Other Study ID Numbers: HPTN 117; UM1AI068619 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For studies within two years of primary objective(s) publication, de-identified individual participant data that underlie results in a publication, will be provided upon request. For studies more than two years from the primary objective(s) publication, de-identified datasets will be available upon request (Public Use Datasets).
• IPD Sharing Time Frame: Investigators may request de-identified datasets in order to duplicate published results, as required by specific journals. Otherwise, de-identified datasets will be made available upon request, two years following publication of the primary results manuscript.
• IPD Sharing Access Criteria: Researchers may submit a request for access to data that has informed published results, by sending an email to HPTN-Data-Access@scharp.org. To access available de-identified datasets, investigators must complete the request form on the Atlas website. Researchers of approved requests will need to sign an HPTN Data Use Agreement before receiving the data and agree to use the provided acknowledgement statement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No