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Pre-Exposure Prophylaxis (PrEP) Adherence Monitoring Using Dried Blood Spots (DOT-DBS)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02022657
First Posted: December 30, 2013
Last Update Posted: April 27, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
San Francisco Department of Public Health
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
University of Colorado, Denver
  Purpose
The primary objective of this study is to define the mean, variance, and dose proportionality for tenofovir-diphosphate(TFV-DP) in dried blood spots resulting from 33%, 67%, and 100% of daily dosing with 200mg emtricitabine and 300mg of tenofovir disoproxil fumarate (as Truvada®). With this information, a model will be established to predict adherence rates to TFV-DP using DBS. Forty-eight healthy HIV-uninfected adult participants who are at low risk for HIV infection will be randomized to one of 6 sequences consisting of two directly observed dosing regimens, 33%/67%, 33%/100%, 67%/33%, 67%/100%, 100%/33%, and 100%/67% with each dose regimen lasting approximately 12 weeks, separated by an approximately 12 week washout period. DBS will be collected at regular intervals, including during the washout. The hypothesis of the study is that levels of TFV-DP in DBS will predict adherence rates in the preceding 1-3 months.

Condition Intervention Phase
PrEP Adherence Monitoring Drug: Truvada Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: PrEP Adherence Monitoring Using Dried Blood Spots

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • TFV-DP pharmacokinetics for different dosing patterns of Truvada [ Time Frame: Assessed every 2 weeks during the dosing periods and at steady-state, week 12 for the first dosing period and week 36 for the second dosing period. ]
    Define the mean, variance, and dose proportionality for TFV-DP in DBS for 33%, 67%, 100% of daily dosing.

  • Establish a model to predict adherence rate by TFV-DP in DBS [ Time Frame: After completion of the study ]
    Using the DBS data from the participants assigned to 33%, 67%, or 100% dosing regimen, construct a mathematical model that can be used to assess adherence based on drug levels found in DBS sample.


Secondary Outcome Measures:
  • "intermittent" versus "holiday" pattern of dosing [ Time Frame: Assessed during the dosing periods (every 2 weeks) and at steady-state (weeks 12 and 36). ]
    Drug levels will be evaluated to predict the intermittent or holiday pattern of dosing.

  • Describe tenofovir and emtricitabine pharmacokinetics [ Time Frame: Assessed every 2 weeks on the first dosing period, then every 3 weeks during the washout, then every 2 weeks during the second dosing period. ]
    Concentrations of drug and relationships will be examined in plasma, Red Blood Cells (RBC), peripheral blood monocyte (PBMC), and hair. Covariates that predict concentrations and relationships will be evaluated.

  • Fingerstick DBS versus DBS from venipuncture [ Time Frame: Assessed at weeks 2, 12, and 28. ]
    Paired DBS collected by fingerstick and venipuncture will be compared.

  • Interpret DBS concentrations from PrEP demonstration projects [ Time Frame: after study completion ]
    The model described under primary outcome 2 will be used to interpret DBS concentrations collected in PrEP demonstration projects.


Enrollment: 34
Actual Study Start Date: April 2014
Study Completion Date: January 2017
Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 33%/67%
Participants will be randomized to one of 6 sequences consisting of two directly observed dosing regimens expressed as % of daily dosing of Truvada
Drug: Truvada
Truvada is a combination pill consisting of tenofovir and emtricitabine used in PrEP
Other Names:
  • Tenofovir
  • Emtricitabine
Active Comparator: 33%/100%
Participants will be randomized to one of 6 sequences consisting of two directly observed dosing regimens expressed as % of daily dosing of Truvada
Drug: Truvada
Truvada is a combination pill consisting of tenofovir and emtricitabine used in PrEP
Other Names:
  • Tenofovir
  • Emtricitabine
Active Comparator: 67%/33%
Participants will be randomized to one of 6 sequences consisting of two directly observed dosing regimens expressed as % of daily dosing of Truvada
Drug: Truvada
Truvada is a combination pill consisting of tenofovir and emtricitabine used in PrEP
Other Names:
  • Tenofovir
  • Emtricitabine
Active Comparator: 67%/100%
Participants will be randomized to one of 6 sequences consisting of two directly observed dosing regimens expressed as % of daily dosing of Truvada
Drug: Truvada
Truvada is a combination pill consisting of tenofovir and emtricitabine used in PrEP
Other Names:
  • Tenofovir
  • Emtricitabine
Active Comparator: 100%/33%
Participants will be randomized to one of 6 sequences consisting of two directly observed dosing regimens expressed as % of daily dosing of Truvada
Drug: Truvada
Truvada is a combination pill consisting of tenofovir and emtricitabine used in PrEP
Other Names:
  • Tenofovir
  • Emtricitabine
Active Comparator: 100%/67%
Participants will be randomized to one of 6 sequences consisting of two directly observed dosing regimens expressed as % of daily dosing of Truvada
Drug: Truvada
Truvada is a combination pill consisting of tenofovir and emtricitabine used in PrEP
Other Names:
  • Tenofovir
  • Emtricitabine

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Ambulatory 18-50 year old adults. Enrollment will target approximately half women and approximately one third African-Americans and one third Latino.
  2. Ability to comply with study procedures, including directly observed dosing visits and availability and use of audio-video streaming technology.

Exclusion Criteria:

  1. Inability to give informed consent
  2. A minimum scalp hair length of 2 cm in the occipital region.
  3. Pregnancy or plan to become pregnant or unwillingness to use birth control
  4. Current breastfeeding.
  5. High risk of HIV-1 infection (for example: sexually active with an HIV infected partner; men who have sex with men who may engage in condom-less intercourse with HIV-infected partners or partner of unknown status during the study; males or females who exchange sex for money, shelter, or gifts; active injection drug use or during the last 12 months; newly diagnosed sexually transmitted infections in last 6 months)
  6. Positive screening HIV+ ELISA or suspected acute HIV infection in the opinion of the clinician. (example signs and symptoms of acute HIV infection include combinations of fever, headache, fatigue, arthralgia, vomiting, myalgia, diarrhea, pharyngitis, rash, night sweats, and adenopathy cervical or inguinal)
  7. Positive Hepatitis B (HBV) surface antigen test at screening
  8. Active psychiatric illness, social condition, or alcohol/drug abuse that, in the opinion of the investigators, would interfere with study requirements.
  9. History of non-traumatic, pathologic bone fractures
  10. Glomerular Filtration Rate (GFR, creatinine clearance) < 60 ml/min (MDRD equation).
  11. Urine dipstick protein ≥ 2+
  12. Total bilirubin and/or hepatic transaminases (ALT and AST) ≥ 2.5x upper limit of normal
  13. Absolute neutrophil count ≤ 1,500/mm3, platelets count ≤ 100,000/mm3, or hemoglobin ≤ 10 g/dL.
  14. Medical condition that alters red blood cell kinetics including hemoglobinopathies or active hemolysis.
  15. Any laboratory value or uncontrolled medical conditions that would interfere with the study conditions such as, heart disease and/or cancer.
  16. Contraindicated concomitant medications (including investigational agents, aminoglycosides, ganciclovir/valganciclovir, chronic high-dose acyclovir/valacyclovir, cyclosporine, amphotericin B, foscarnet, and cidofovir, and products with same or similar active ingredients as the study medications (Truvada®) including ATRIPLA®, COMPLERA®, EMTRIVA®, VIREAD®; or drugs containing lamivudine or adefovir, which are close analogs of Emtricitabine (FTC) and tenofovir, respectively).
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02022657


Locations
United States, California
University of California San Francisco/San Francisco Department of Public Health
San Francisco, California, United States, 94102
United States, Colorado
University of Colorado Denver
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
San Francisco Department of Public Health
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Peter L Anderson, PharmD University of Colorado, Denver
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT02022657     History of Changes
Other Study ID Numbers: 13-0427
U01AI106499 ( U.S. NIH Grant/Contract )
First Submitted: December 9, 2013
First Posted: December 30, 2013
Last Update Posted: April 27, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No plan to share IPD

Keywords provided by University of Colorado, Denver:
Pre exposure prophylaxis
Dried blood spots

Additional relevant MeSH terms:
Tenofovir
Emtricitabine
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents