Characterization of Doxycycline Pharmacokinetics and Adherence

NCT07755618 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: HPTN 117UM1AI068619
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sexually Transmitted Infection

Keywords

Doxycycline; Pharmacokinetics; PK Sampling

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (34)

• Number of gastrointestinal (GI)-related adverse events reported after doxycycline hyclate dosing during the multiple dose phase.

  Study visit days 14-23

• Number of gastrointestinal (GI)-related adverse events reported after doxycycline hyclate dosing after the multiple dose phase.

  Up to 14 days post last dose.

• Maximum observed dried blood spot (DBS) concentration (Cmax) for 200mg doxycycline hyclate after a single dose.

  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.

  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.

  1, 2, 3, 4, 6, 8, 24, 72, 96, 168, 240, and 336 hours post dose.

Study Arms (4)

Single-Dose PK Phase- 200mg delayed release (DR) doxycycline tablet

EXPERIMENTAL

Participants in this arm will take one 200 mg delayed release (DR) doxycycline hyclate tablet

Drug: Single-Dose PK Phase - DR Group

Multi-Dose PK Phase- daily dosing (every 24 hours)

EXPERIMENTAL

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

Single Dose PK Phase- Two 100mg immediate release (IR) doxycycline tablets

EXPERIMENTAL

Participants in this arm will take two 100mg immediate release (IR) doxycycline hyclate tablets

Drug: Single-Dose PK Phase - IR Group

Multi-dose PK Phase- Intermittent (every 72 hours) dosing

EXPERIMENTAL

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

Interventions

Single-Dose PK Phase - DR Group DRUG

One 200 mg doxycycline hyclate delayed release (DR) tablet

Single-Dose PK Phase- 200mg delayed release (DR) doxycycline tablet

Multi-Dose PK Phase - Intermittent Group DRUG

One 200 mg doxycycline hyclate delayed release (DR) tablet every 72 hours

Multi-dose PK Phase- Intermittent (every 72 hours) dosing

Single-Dose PK Phase - IR Group DRUG

Two 100 mg doxycycline hyclate immediate-release (IR) tablets

Single Dose PK Phase- Two 100mg immediate release (IR) doxycycline tablets

Multi-Dose PK Phase - Daily Group DRUG

One 200 mg doxycycline hyclate delayed release (DR) tablet every 24 hours

Multi-Dose PK Phase- daily dosing (every 24 hours)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• HIV Prevention Trials Network: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Conditions

Sexually Transmitted Diseases

Condition Hierarchy (Ancestors)

Communicable Diseases; Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mackenzie Cottrell, PharmD, MS

  University of North Carolina, Chapel Hill

  STUDY CHAIR

• Mark Marzinke, PhD

  Johns Hopkins University

  STUDY CHAIR

Central Study Contacts

Busola Akingbade, MPH

CONTACT

919-321-3344; bakingbade@fhi360.org

Michelle Robinson

CONTACT

919-321-3585; mrobinson@fhi360.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Sixteen (16) participants (approximately 8 males and 8 females) will undergo two randomization sequences upon enrollment into the study. In the single dose phase, participants will be randomized (1:1) to take a dose of 200mg doxycycline hyclate as either 1) 1x 200mg delayed release (DR) tablet or 2) 2x100mg immediate release (IR) tablets. Following administration of this single dose, participants will undergo semi-intensive PK sampling over a 14-day period. In the multiple dose phase, participants will also be randomized (1:1) to receive 200mg doxycycline hyclate (as a DR tablet) either daily (every 24 hours) or intermittently (every 72 hours) for 10 days. Both randomizations (IR vs DR and daily vs intermittent frequency) will be stratified by sex. All doses will be directly observed by study staff. Participants will be followed for 14 days after their last dose. PK sampling will occur at designated times over the course of the study.

Study Record Dates

• First Submitted: August 5, 2026
• First Posted: August 10, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: August 10, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• 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.

Locations

US (1)