Quantification of Estradiol's Impact on Nucleotides in Cellular Populations of the Lower GI Tract

NCT03917420 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 19-0333R21AI145646
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose: To Assess the impact of high and low in vivo estradiol exposure on PrEP (Pre-exposure prophylaxis) nucleotide concentrations in different cellular populations of the lower GI (gastrointestinal) tract and to quantify the relationship between estradiol, progesterone, and testosterone on PrEP nucleotide concentrations in rectal and peripheral blood mononuclear cells. As well as the relationship between estradiol, progesterone, and testosterone on PrEP concentrations in plasma. Participants: Healthy, cisgender female, volunteers, aged 18-49 inclusive on the date of screening with an intact gastrointestinal system and regular menstrual cycle. Procedures (methods): Participants will take a single daily dose of study drug for five days before each sampling visit. The visits will be scheduled during the early follicular phase of the menstrual cycle (approximately days 2-5 after the first day of menses, Visit 1) when estradiol is predicted to be the lowest and the late follicular phase (approximately days 12-15 after the first day of menses, Visit 2) when estradiol is predicted to be highest. Samples of blood, rectal cells, and rectal tissue will be collected at both Visits 1 and 2. All participants will complete a follow-up safety visit within 14 days of completing study sampling.

Conditions

HIV/AIDS

Outcome Measures

Primary Outcomes (4)

• Average Tenofovir Diphosphate Concentrations in Mixed Rectal Cells During the Early (Low Estradiol) Follicular Phases of the Menstrual Cycle.

  Average tenofovir diphosphate concentrations measured in mixed rectal cells collected via cytobrush during the early (low estradiol) follicular phases of the menstrual cycle reported in Fmol/million cells.

  Days 2-5

• Average Tenofovir Diphosphate Concentrations Measured in Mixed Rectal Cells During the Late (High Estradiol) Follicular Phases of the Menstrual Cycle.

  Average tenofovir diphosphate concentrations measured in mixed rectal cells collected via cytobrush during the late (high estradiol) follicular phases of the menstrual cycle reported in Fmol/million cells

  Days 12-15

• Average Emtricitabine Triphosphate Concentrations Measured in Mixed Rectal Cells During the Early (Low Estradiol) Follicular Phases of the Menstrual Cycle.

  Average emtricitabine triphosphate concentrations measured in mixed rectal cells collected via cytobrush during the early (low estradiol) follicular phases of the menstrual cycle reported in Fmol/million cells.

  Days 2-5

• Average Emtricitabine Triphosphate Concentrations Measured in Mixed Rectal Cells During the Late (High Estradiol) Follicular Phases of the Menstrual Cycle.

  Average emtricitabine triphosphate concentrations measured in mixed rectal cells collected via cytobrush during the late (high estradiol) follicular phases of the menstrual cycle reported in Fmol/million cells.

  Days 12-15

Secondary Outcomes (7)

• Average Estradiol Concentrations in Serum.

  Day 5

• Average Progesterone Concentrations in Serum.

  Day 5

• Average Testosterone Concentrations in Serum.

  Day 5

• Average Tenofovir Diphosphate Concentrations in Peripheral Blood Mononuclear Cells.

  Day 5

• Average Emtricitabine Concentrations in Peripheral Blood Mononuclear Cells.

  Day 5

Study Arms (1)

Tenofovir/Emtricitabine

EXPERIMENTAL

Participants will take 5 once daily doses above noted combination tab at 200mg/300mg before each sampling visit

Drug: Tenofovir 300Mg Oral Tablet; Drug: Emtricitabine 200 MG

Interventions

Tenofovir 300Mg Oral Tablet DRUG

Once daily dose of the combo tab x 5 days pre-sampling

Also known as: Truvada

Tenofovir/Emtricitabine

Emtricitabine 200 MG DRUG

Once daily dose of the combo tab x 5 days pre-sampling

Also known as: Truvada

Tenofovir/Emtricitabine

Eligibility Criteria

• Age: 18 Years - 49 Years
• Gender Eligibility Details: Only cisgender pre-menopausal females will be eligible to enroll
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy cisgender pre-menopausal female participants between the ages of 18 and 49 years, inclusive on the date of screening (Healthy is defined as no irregular menstrual cycles or clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, and clinical laboratory tests.
• Regular menstrual cycles defined as at least 1 day of menses occurring every 21-35 days)
• Estimated calculated creatinine clearance (eCcr) of at least 60 mL/min by the Cockcroft-Gault formula where: eCcr (female) in mL/min = \[(140 - age in years) x (weight in kg) x 0.85\] / (72x serum creatinine in mg/dL).
• Negative serum pregnancy test at screening
• All participants should be using at least one of the following methods of contraception\* from the screening visit through 72 hours prior to inpatient admission (at which time the women will be asked to remain abstinent until after their follow-up visit):
• Non continuous systemic hormonal contraceptives that permit intermittent menstruation
• IUD (non-hormonal intrauterine device) placed at least 1 month prior to study enrollment
• Bilateral tubal ligation (Sterilization)
• Vasectomized male partners
• Condom + Spermicide
• \*Unless engaged in sexual activity with female only sex partners or abstinent for at least 3 months prior with no intention of becoming sexually active during the study period. Any history of recent or present concomitant male sex partners will be addressed and ruled out in the context of screening participants for eligibility for the protocol
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial.
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
• Subject must be willing to abstain from sexual intercourse, and all and intrarectal objects and products for at least 72 hours prior to Sampling #1 until study completion.
• Subject must be HIV-1 and Hepatitis B and C negative as documented on screening labs.

You may not qualify if:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including documented drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
• Participants with a history of hysterectomy
• Participants who are pregnant, possibly pregnant or lactating
• History of febrile illness within five days prior to first dose.
• Any condition possibly affecting drug absorption (eg, gastrectomy or other significant alterations of the gastrointestinal tract)
• A positive urine drug screen.
• An untreated-positive test for syphilis, gonorrhea, or Chlamydia at screening.
• Any clinically relevant laboratory chemistry or hematology result Grade 2 or greater according to the Division of AIDS Laboratory Grading Tables
• Treatment with an investigational drug within 4 months preceding the first dose of study product.
• History of regular alcohol consumption exceeding 14 drinks (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of spirits) per week.
• Participation in a clinical trial involving rectal biopsies within 6 months preceding the first dose of trial medication.
• Blood donation of approximately 1 pint (500 mL) within 56 days prior to dosing.
• Any condition which, in the opinion of the investigator, is likely to interfere with follow-up or ability to take the study medication appropriately.
• Unwilling or unable to comply with the dietary and concomitant drug restrictions in regard to study drug administration as outlined in the study procedures and prohibited medications sections.
• Women utilizing continuous hormonal contraception options such as Seasonique, injectables, implants, and hormonal IUDs

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: 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

Acquired Immunodeficiency Syndrome

Interventions

Tenofovir; Tablets; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations

Results Point of Contact

• Title: Amanda Poliseno
• Organization: UNC Chapel Hill

amanda_poliseno@unc.edu

919-962-5344

Study Officials

• Mackenzie Cottrell, PharmD, MS

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2019
• First Posted: April 17, 2019
• Study Start: March 26, 2019
• Primary Completion: September 4, 2019
• Study Completion: September 4, 2019
• Last Updated: April 12, 2023
• Results First Posted: April 12, 2023

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Upon acceptance of final manuscript for publication for an indefinite time period
• Access Criteria: Before data will be shared, a data use agreement will be put in place in accordance with local regulations. The requestor will need to obtain appropriate ethics approval.

Locations

US (1)