Dose-Proportionality and Intra-Individual Variability of Intracellular TFV-DP and FTC-TP in Healthy Volunteers

NCT01276600 | Completed Phase 1 DMC

• 1 other identifier: HPTN 066
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

Describe the dose-proportionality and intra-individual variability of tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) at steady-state in healthy human participants taking Truvada® (FTC 200mg/TDF 300 mg) under direct observation.

Conditions

HIV

Outcome Measures

Primary Outcomes (2)

• Assess dose-proportionality

  Assess dose-proportionality of intracellular TFV-DP and FTC-TP from weekly to daily dosing (Arms 1-4).

  49 days

• Comparison of intra-individual variability--days 28 and 35

  Describe intra-individual variability in intracellular TFV-DP and FTC-TP concentrations at steady-state (comparison of Day 28 and Day 35).

  Days 28 and 35

Secondary Outcomes (3)

• Determine relationship between pre-dose and decaying concentrations

  Days 35 and 49

• Determine differences between men and women

  49 days

• Safety profiles

  49 days

Study Arms (4)

Arm 1

EXPERIMENTAL

1 tablet orally weekly

Drug: Emtricitabine/tenofovir

Arm 2

EXPERIMENTAL

One tablet orally twice weekly

Drug: Emtricitabine/tenofovir

Arm 3

EXPERIMENTAL

Two tablets orally twice weekly

Drug: Emtricitabine/tenofovir

Arm 4

EXPERIMENTAL

One tablet orally daily

Drug: Emtricitabine/tenofovir

Interventions

Emtricitabine/tenofovir DRUG

200mg of emtricitabine 300mg of tenofovir

Arm 1; Arm 2; Arm 3; Arm 4

Eligibility Criteria

• Age: 18 Years - 44 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• to 44 years of age, inclusive on the date of screening.
• Provides informed consent for the study.
• Non-reactive HIV rapid test results at the screening and enrollment visits.
• An estimated calculated creatinine clearance (eCcr) at least 70 mL/min by the Cockcroft-Gault formula where:
• eCcr (female) in mL/min = \[(140 - age in years) x (weight in kg) x 0.85\] / (72 x serum creatinine in mg/dL).
• eCcr (male) in mL/min = \[(140 - age in years) x (weight in kg)\] / (72 x serum creatinine in mg/dL).
• Participants are sexually active, defined as at least one sex (vaginal or anal intercourse) act in the 30 days prior to screening.
• Participants must agree to use condoms for all coital events during study participation.
• Intensive sampling cohort only:
• Not using spermicide as a means of birth control (in conjunction with a condom or diaphragm)
• Women must:
• Be pre-menopausal
• Have regular menstrual cycles with at least 21 days between menses (unless on contraception that causes amenorrhea or irregular menses)
• Have a negative urine pregnancy test at screening and enrollment
• Be utilizing an alternative method of birth control in addition to condoms (hormonal contraceptive, diaphragm or have undergone surgical sterilization) or have a vasectomized exclusive male partner.

You may not qualify if:

• At screening::
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 1.5 X the site laboratory ULN (upper limit of normal)
• Hemoglobin less than 10.0 g/dL
• Platelet count less than 100,000/mm3
• Serum phosphate level below site laboratory LLN (lower limit of normal)
• INR or aPTT greater than site laboratory ULN
• Other safety tests (bicarbonate (HCO3), potassium (K), chloride (Cl), sodium (Na), calcium (Ca), fasting glucose) with results outside of the laboratories reference range
• + or greater protein on urine dipstick testing
• + or greater glucose on urine dipstick testing
• Culture-confirmed urinary tract infection
• Co-enrollment in any other HIV interventional research study (excluding behavioral only interventions) or prior enrollment in the active arm of a HIV vaccine trial.
• Clinically apparent or patient report of active skin disorders including: rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, and pustular rash.
• Women who are pregnant or breastfeeding.
• One or more reactive HIV rapid test results at screening or enrollment, even if HIV infection is not confirmed.
• Positive hepatitis B surface antigen (HBsAg) test.

Sponsors & Collaborators

• HIV Prevention Trials Network: lead

Study Sites (2)

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Interventions

Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Intervention Hierarchy (Ancestors)

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

Study Officials

• Craig Hendrix, MD

  Johns Hopkins University

  STUDY CHAIR

• Kristine Patterson, MD

  University of North Carolina

  STUDY CHAIR

• Kenneth Mayer, MD

  Brown University

  STUDY CHAIR

• Adriana Andrade, MD, MPH

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 12, 2011
• First Posted: January 13, 2011
• Study Start: January 1, 2011
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: March 25, 2025

Record last verified: 2025-03

Locations

US (2)