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CompletedNCT01687218Updated Jun 24, 2021Results posted

Safety and Acceptability Study of Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet and Rectally-Applied Tenofovir Reduced-Glycerin 1% Gel

A Phase 2 interventional study of Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet) and Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel) in HIV, sponsored by CONRAD. Completed at 8 sites in 5 countries. Open to male participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-06-24.

Sponsored by CONRAD · Phase 2, Interventional, and Other

Phase
Phase 2
Study type
Interventional
Enrollment
195
Allocation
Randomized
Ages
18 Years and older
Sex
Male
01

Study summary

MTN-017 is a Phase 2, multi-site, randomized, six-sequence, two three-period, open label crossover study, examining the effects of oral Truvada and reduced glycerin 1% tenofovir gel. The study population will be sexually active, HIV-uninfected males who are 18 years of age or older, who report a history of receptive anal intercourse in the past 3 months. Each of the study product regimens offers different advantages to participants seeking an effective HIV prevention agent. How these relative advantages will compare in terms of safety, acceptability, systemic and local absorption, and adherence will be examined within this study.

02

Conditions studied

  • HIV
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Male
Accepts healthy volunteers
Yes

Inclusion criteria

  1. Male or transgender female > age of 18 at Screening
  2. Able and willing to provide written informed consent
  3. HIV-1 uninfected at Screening and Enrollment
  4. Able and willing to provide adequate locator information, as defined in site SOP
  5. Available to return for all study visits, barring unforeseen circumstances and willing to comply with study participation requirements
  6. In general good health at Screening and Enrollment, as determined by the site IoR or designee
  7. Per participant report, a history of consensual RAI at least once in the past 3 months
  8. Per participant report at Screening and Enrollment, agrees not to engage in receptive or insertive sexual activity with another study participant for the duration of study participation.
  9. Willing to use study-provided condoms for the duration of the study for penetrative intercourse
  10. Willing to not take part in other research studies involving drugs, medical devices, vaccines or genital products for the duration of study participation (including the time between Screening and Enrollment)

  11. Men and transgender females who agree to take part in the PK, PD and Mucosal Immunology Subset, must also agree to abstain from:

    • Inserting anything into the rectum, including abstaining from RAI for 72 hours after the collection of biopsies
    • Taking non-steroidal anti-inflammatory drugs (NSAIDs), aspirin and/or other drugs that are associated with increased likelihood of bleeding following mucosal biopsy collection for 72 hours prior to and following the collection of biopsies.

Exclusion criteria

Exclusion Criteria:

  1. At Screening, participant-reported symptoms, and/or clinical or laboratory diagnosis of active anorectal or reproductive tract infection requiring treatment per current World Health Organization (WHO) guidelines or symptomatic urinary tract infection (UTI). Infections requiring treatment include symptomatic Chlamydia trachomatis (CT) infection, Neisseria gonorrhea (GC), syphilis, active herpes simplex virus (HSV) lesions, anogenital sores or ulcers, or symptomatic genital warts.

    Note: HSV-1 or HSV-2 seropositive diagnosis with no active lesions is allowed, since treatment is not required.

    In cases of non-anorectal GC/CT identified at screening, one re-screening 2 months after the screening visit will be allowed

  2. History of inflammatory bowel disease as reported by participant history

  3. At Screening:

    • Positive for hepatitis B surface antigen
    • Positive for hepatitis C antibody
    • Hemoglobin \< 10.0 g/dL
    • Platelet count less than 100,000/mm3
    • White blood cell count \< 2,000 cells/mm3 or > 15,000 cells/mm3
    • Calculated creatinine clearance less than 60 mL/min by the Cockcroft-Gault formula where creatinine clearance in mL/min = (140 - age in years) x (weight in kg) x (1 for male)/72 x (serum creatinine in mg/dL)
    • Serum creatinine > 1.3 x the site laboratory upper limit of normal (ULN)
    • Alanine transaminase (ALT) and/or aspartate aminotransferase (AST) > 2.5× the site laboratory ULN
    • PK, PD and Immunological Subset only: International normalized ratio (INR) > 1.5× the site laboratory ULN or partial thromboplastin time (PTT) > 1.25× the site laboratory ULN
  4. Known allergy to methylparaben and/or propylparaben
  5. Known allergy to any of the study products.

  6. Per participant report, use of the following medications and/or products within 12 weeks prior to screening, and/or anticipated use or unwillingness to abstain from use throughout study participation:

    • Any investigational products
    • Systemic immunomodulatory medications
    • Use of Heparin, including Lovenox®
    • Warfarin
    • Plavix® (clopidogrel bisulfate)
    • Rectally-administered medications or products, containing N-9 or corticosteroids
  7. By participant report, use of post-exposure prophylaxis (PEP) for HIV exposure within the 12 weeks prior to screening or anticipated use during study participation.
  8. Symptoms suggestive of acute HIV seroconversion at Screening and Enrollment
  9. Has any other condition that, in the opinion of the Investigator of Record (IoR)/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives would make the patient unsuitable for the study or unable/unwilling to comply with the study requirements. Such conditions may include, but are not limited to, colorectal abnormalities, substance abuse, or renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological or psychiatric disease.
04

Study design

Phase
Phase 2
Primary purpose
Other
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
195 participants (actual)

Study arms

  • Active comparator
    Group 1

    Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks); followed by Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks)

    Drug: Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet) · Drug: Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel) · Drug: Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)

  • Active comparator
    Group 2

    Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks); followed by Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks)

    Drug: Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet) · Drug: Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel) · Drug: Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)

  • Active comparator
    Group 3

    Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks)

    Drug: Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet) · Drug: Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel) · Drug: Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)

  • Active comparator
    Group 4

    Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks); followed by Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks)

    Drug: Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet) · Drug: Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel) · Drug: Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)

  • Active comparator
    Group 5

    Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks); followed by Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks)

    Drug: Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet) · Drug: Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel) · Drug: Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)

  • Active comparator
    Group 6

    Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks);followed by Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks)

    Drug: Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet) · Drug: Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel) · Drug: Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)

Interventions

  • DrugOral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet)
  • DrugRectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel)
  • DrugRectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)
05

What researchers measure

Primary outcomes

  1. Safety: Grade 2 or Higher Adverse Events

    Compare the safety profiles of daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel. Analysis of the primary endpoint of grade 2 or higher AEs was performed on only the evaluable participants based on the principle of intent-to-treat (ITT) whereby participants who were randomized were included in the analysis regardless of whether or not they received product in a given period (i.e, were lost to follow-up, or terminated early and/or were on a product hold).

    Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)

  2. Acceptability: Participant Self-report of Liking the Product. H1-Overall How do You Feel About the Product You Used Recently?

    To evaluate and compare acceptability of daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel. Consistent with the acceptability endpoint of liking the product, a variable was created by combining from Section H. Liking the Product of the MTN-017 Follow-up Behavioral Questionnaire question 1A and question 1BC. Categories 1 and 2 were combined and categories 3 and 4 were combined to create a dichotomous variable.

    Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)

  3. Acceptability: Participant Self-report of Ease of Use. I1-Overall How Easy or Difficult Was it to Use the Product?

    To evaluate and compare acceptability of daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel. Consistent with the acceptability endpoint of ease of use, a variable was created to compare regimens. This variable combines questions 1A and 1BC from Section I. Ease of Use of the MTN-017 Follow-up Behavioral Questionnaire. Categories 1 and 2 were combined and categories 3 and 4 were combined to create dichotomous variables.

    Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)

  4. Acceptability: Participant Self-report of Likelihood of Product Use if Shown to be Effective. N1-If This Product Provides Some Protection How Likely Would You be to Take it?

    To evaluate and compare acceptability of daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel. Consistent with the acceptability endpoint of likelihood to use product in the future, a variable was created by combining Section N. Likelihood to Use Product in the Future of the MTN-017 Follow-up Behavioral Questionnaire questions 1A, 1B, and 1C. Categories 1 and 2 were combined and categories 3 and 4 were combined to create a dichotomous variable.

    Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)

Secondary outcomes

  1. Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mL) in Blood Plasma

    Compare tenofovir concentrations in blood plasma among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.

    Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)

  2. Pharmacokinetics: End Period Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Tissue

    Compare end period tenofovir concentrations in rectal tissue among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.

    Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)

  3. Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Sponge

    Compare tenofovir concentrations in rectal sponge specimens among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.

    Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)

  4. Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mL) in Blood Plasma

    Compare emtricitabine concentrations in blood plasma among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.

    Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)

  5. Pharmacokinetics: End Period Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Tissue

    Compare end period emtricitabine concentrations in rectal tissue among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.

    Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)

  6. Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Sponge

    Compare emtricitabine concentrations in rectal sponge among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.

    Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)

  7. Pharmacokinetics: End Period Tenofovir-Diphosphate (TFV-DP) Concentrations (log10 ng/mg) in Rectal Tissue

    Compare end period tenofovir-diphosphate (TFV-DP) concentrations in rectal tissue among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.

    Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)

  8. Adherence: Percentage of Prescribed Doses Taken Orally or Administered Rectally in an 8-week Period

    Compare percentage of prescribed doses taken orally or administered rectally in an 8-week period based on the Final Converged Rates. Final Converged Rates were measured first via self-report through Short Message Service (SMS). The clinic staff also reported the most likely number of doses taken. Finally, the MTN Behavioral Research Working Group (BRWG) provided the final estimate of the number of doses taken for each participant for each period based on self-report, staff estimates and PK testing results. Note that these final judgement data are missing if PK results are missing.

    Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)

Other outcomes

  1. Pharmacodynamics

    To characterize pharmacodynamic responses following oral and rectal exposure to antiretroviral drugs

    Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)

  2. Mucosal Immunity

    To characterize changes in mucosal immunity between baseline and the end of the daily FTC/TDF and TFV RG 1% gel product use

    Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)

  3. Correlation Between PK and Adherence

    To assess correlation of PK with adherence measures

    Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)

  4. Factors Associated With Adherence

    To identify factors associated with product adherence and whether they differ by product used (FTC/TDF or TFV RG 1% gel) or regimen (daily use or RAI-associated use)

    Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)

  5. Sexual Activity and Condom Use

    To examine whether sexual activity or condom use varies by product used

    Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)

  6. Product Sharing

    To determine the level of sharing of study products with non-participants and to assess with whom products are shared

    Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)

  7. Problem Practices

    To determine the prevalence of behavioral practices associated with anal intercourse that may affect microbicide use

    Time frame: 27 weeks (three 8-week product use periods with 1-week washout periods between them)

06

Results

Posted Feb 1, 2017

Participant flow

HIV-uninfected males or transgender females who were 18 years of age or older who practice receptive anal intercourse were recruited from September 2013 through November 2014 from 8 sites in Peru, Puerto Rico, South Africa, Thailand and USA.

Participant flow — Overall Study
MilestoneGroup 1Group 2Group 3Group 4Group 5Group 6
Started333231343332
Completed302930323232
Not completed331210
Withdrew: Withdrawal by subject230110
Withdrew: Relocated, no follow-up planned101100

Outcome measures

PrimarySafety: Grade 2 or Higher Adverse Events

Compare the safety profiles of daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel. Analysis of the primary endpoint of grade 2 or higher AEs was performed on only the evaluable participants based on the principle of intent-to-treat (ITT) whereby participants who were randomized were included in the analysis regardless of whether or not they received product in a given period (i.e, were lost to follow-up, or terminated early and/or were on a product hold).

Time frame:
27 weeks (three 8-week product use periods with 1-week washout periods between them)
Reported as:
Number · participants
Safety: Grade 2 or Higher Adverse Events
participantsProduct 1Product 2Product 3
Safety: Grade 2 or Higher Adverse Events646156
Statistical analysis
  • Product 1 vs Product 2 · Generalized Estimating Equation (GEE) · p = 0.88 · Risk ratio (rr): 1.03 · 95% CI 0.73 to 1.44It shows the rate ratio (RR) based on a GEE model comparing the Daily Rectal regimen with the Oral regimen and controlling for period in the model.
  • Product 1 vs Product 3 · Generalized Estimating Equation (GEE) · p = 0.43 · Risk ratio (rr): 0.88 · 95% CI 0.64 to 1.21It shows the rate ratio (RR) based on a GEE model comparing the RAI Rectal regimen with the Oral regimen and controlling for period in the model.
PrimaryAcceptability: Participant Self-report of Liking the Product. H1-Overall How do You Feel About the Product You Used Recently?

To evaluate and compare acceptability of daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel. Consistent with the acceptability endpoint of liking the product, a variable was created by combining from Section H. Liking the Product of the MTN-017 Follow-up Behavioral Questionnaire question 1A and question 1BC. Categories 1 and 2 were combined and categories 3 and 4 were combined to create a dichotomous variable.

Time frame:
27 weeks (three 8-week product use periods with 1-week washout periods between them)
Reported as:
Number · participants
Acceptability: Participant Self-report of Liking the Product. H1-Overall How do You Feel About the Product You Used Recently?
participantsProduct 1Product 2Product 3
Disliked Very Much/A Little164738
Liked Very Much/A Little163134145
Statistical analysis
  • Product 1 vs Product 2 · Generalized Estimating Equation (GEE) · p = <0.0001 · Odds ratio (or): 0.28 · 95% CI 0.15 to 0.50Oral regimen is the reference group.
  • Product 1 vs Product 3 · Generalized Estimating Equation (GEE) · p = 0.002 · Odds ratio (or): 0.37 · 95% CI 0.20 to 0.70Oral regimen is the reference group.
PrimaryAcceptability: Participant Self-report of Ease of Use. I1-Overall How Easy or Difficult Was it to Use the Product?

To evaluate and compare acceptability of daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel. Consistent with the acceptability endpoint of ease of use, a variable was created to compare regimens. This variable combines questions 1A and 1BC from Section I. Ease of Use of the MTN-017 Follow-up Behavioral Questionnaire. Categories 1 and 2 were combined and categories 3 and 4 were combined to create dichotomous variables.

Time frame:
27 weeks (three 8-week product use periods with 1-week washout periods between them)
Reported as:
Number · participants
Acceptability: Participant Self-report of Ease of Use. I1-Overall How Easy or Difficult Was it to Use the Product?
participantsProduct 1Product 2Product 3
Very Difficult/Difficult142418
Very Easy/Easy169160165
Statistical analysis
  • Product 1 vs Product 2 · Generalized Estimating Equation (GEE) · p = 0.08 · Odds ratio (or): 0.56 · 95% CI 0.29 to 1.08Oral regimen is the reference group.
  • Product 1 vs Product 3 · Generalized Estimating Equation (GEE) · p = 0.46 · Odds ratio (or): 0.76 · 95% CI 0.37 to 1.56Oral regimen is the reference group.
PrimaryAcceptability: Participant Self-report of Likelihood of Product Use if Shown to be Effective. N1-If This Product Provides Some Protection How Likely Would You be to Take it?

To evaluate and compare acceptability of daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel. Consistent with the acceptability endpoint of likelihood to use product in the future, a variable was created by combining Section N. Likelihood to Use Product in the Future of the MTN-017 Follow-up Behavioral Questionnaire questions 1A, 1B, and 1C. Categories 1 and 2 were combined and categories 3 and 4 were combined to create a dichotomous variable.

Time frame:
27 weeks (three 8-week product use periods with 1-week washout periods between them)
Reported as:
Number · participants
Acceptability: Participant Self-report of Likelihood of Product Use if Shown to be Effective. N1-If This Product Provides Some Protection How Likely Would You be to Take it?
participantsProduct 1Product 2Product 3
Very Unlikely/Unlikely245231
Very Likely/Likely159132145
Statistical analysis
  • Product 1 vs Product 2 · Generalized Estimating Equation (GEE) · p = 0.0004 · Odds ratio (or): 0.38 · 95% CI 0.22 to 0.65Oral regimen is the reference group.
  • Product 1 vs Product 3 · Generalized Estimating Equation (GEE) · p = 0.23 · Odds ratio (or): 0.70 · 95% CI 0.39 to 1.25Oral regimen is the reference group.
SecondaryPharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mL) in Blood Plasma

Compare tenofovir concentrations in blood plasma among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.

Time frame:
27 weeks (three 8-week product use periods with 1-week washout periods between them)
Reported as:
Mean · log10 ng/mL
Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mL) in Blood Plasma
log10 ng/mLProduct 1Product 2Product 3
Mid-Period TFV Concentration1.85 ± 0.590.42 ± 0.83-0.01 ± 0.89
End Period TFV Concentration1.77 ± 0.710.37 ± 0.84-0.02 ± 0.92
Statistical analysis
  • Product 1 vs Product 2 · Mixed Models Analysis · p = <0.001 · Slope: -1.41 · 95% CI -1.53 to -1.30This comparison is between the daily rectal and oral (reference) groups for tenofovir levels in blood plasma, log10 ng/mL.
  • Product 1 vs Product 3 · Mixed Models Analysis · p = <0.001 · Slope: -1.82 · 95% CI -1.95 to -1.70This comparison is between the RAI rectal and oral (reference) groups for tenofovir levels in blood plasma, log10 ng/mL.
SecondaryPharmacokinetics: End Period Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Tissue

Compare end period tenofovir concentrations in rectal tissue among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.

Time frame:
27 weeks (three 8-week product use periods with 1-week washout periods between them)
Reported as:
Mean · log10 ng/mg
Pharmacokinetics: End Period Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Tissue
log10 ng/mgProduct 1Product 2Product 3
Pharmacokinetics: End Period Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Tissue0.18 ± 0.510.84 ± 0.500.02 ± 0.87
Statistical analysis
  • Product 1 vs Product 2 · Mixed Models Analysis · p = <0.001 · Slope: 0.66 · 95% CI 0.49 to 0.83Oral regimen is the reference group.
  • Product 1 vs Product 3 · Mixed Models Analysis · p = 0.31 · Slope: -0.16 · 95% CI -0.46 to 0.15Oral regimen is the reference group.
SecondaryPharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Sponge

Compare tenofovir concentrations in rectal sponge specimens among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.

Time frame:
27 weeks (three 8-week product use periods with 1-week washout periods between them)
Reported as:
Mean · log10 ng/mg
Pharmacokinetics: Tenofovir (TFV) Concentrations (log10 ng/mg) in Rectal Sponge
log10 ng/mgProduct 1Product 2Product 3
Initiate Period TFV Concentration-1.53 ± 1.20-1.65 ± 1.12-1.29 ± 1.42
Mid-Period TFV Concentration0.71 ± 1.220.97 ± 1.64-0.03 ± 1.54
End Period TFV Concentration0.66 ± 1.311.00 ± 1.420.01 ± 1.67
Statistical analysis
  • Product 1 vs Product 2 · Mixed Models Analysis · p = 0.004 · Slope: 0.30 · 95% CI 0.10 to 0.50
  • Product 1 vs Product 3 · Mixed Models Analysis · p = <0.001 · Slope: -0.70 · 95% CI -0.92 to -0.47
SecondaryPharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mL) in Blood Plasma

Compare emtricitabine concentrations in blood plasma among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.

Time frame:
27 weeks (three 8-week product use periods with 1-week washout periods between them)
Reported as:
Mean · log10 ng/mL
Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mL) in Blood Plasma
log10 ng/mLProduct 1Product 2Product 3
Mid-Period FTC Concentration2.34 ± 0.82-0.35 ± 1.00-0.37 ± 0.98
End Period FTC Concentration2.25 ± 0.96-0.37 ± 0.98-0.33 ± 1.06
Statistical analysis
  • Product 1 vs Product 2 · Mixed Models Analysis · p = <0.001 · Slope: -2.66 · 95% CI -2.82 to -2.50
  • Product 1 vs Product 3 · Mixed Models Analysis · p = <0.001 · Slope: -2.65 · 95% CI -2.81 to -2.49
SecondaryPharmacokinetics: End Period Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Tissue

Compare end period emtricitabine concentrations in rectal tissue among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.

Time frame:
27 weeks (three 8-week product use periods with 1-week washout periods between them)
Reported as:
Mean · log10 ng/mg
Pharmacokinetics: End Period Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Tissue
log10 ng/mgProduct 1Product 2Product 3
Pharmacokinetics: End Period Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Tissue-0.35 ± 0.33-1.26 ± 0.00-1.26 ± 0.00
Statistical analysis
  • Product 1 vs Product 2 · Mixed Models Analysis · p = <0.001 · Slope: -0.91 · 95% CI -1.01 to -0.80
  • Product 1 vs Product 3 · Mixed Models Analysis · p = <0.001 · Slope: -0.91 · 95% CI -1.01 to -0.80
SecondaryPharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Sponge

Compare emtricitabine concentrations in rectal sponge among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.

Time frame:
27 weeks (three 8-week product use periods with 1-week washout periods between them)
Reported as:
Mean · log10 ng/mg
Pharmacokinetics: Emtricitabine (FTC) Concentrations (log10 ng/mg) in Rectal Sponge
log10 ng/mgProduct 1Product 2Product 3
Initiate Period FTC Concentration-1.75 ± 0.80-1.76 ± 0.73-1.57 ± 1.00
Mid-Period FTC Concentration0.31 ± 1.14-1.76 ± 0.76-1.67 ± 0.91
End Period FTC Concentration0.14 ± 1.30-1.80 ± 0.69-1.69 ± 0.87
Statistical analysis
  • Product 1 vs Product 2 · Mixed Models Analysis · p = <0.001 · Slope: -2.00 · 95% CI -2.16 to -1.84
  • Product 1 vs Product 3 · Mixed Models Analysis · p = <0.001 · Slope: -1.90 · 95% CI -2.07 to -1.74
SecondaryPharmacokinetics: End Period Tenofovir-Diphosphate (TFV-DP) Concentrations (log10 ng/mg) in Rectal Tissue

Compare end period tenofovir-diphosphate (TFV-DP) concentrations in rectal tissue among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel groups.

Time frame:
27 weeks (three 8-week product use periods with 1-week washout periods between them)
Reported as:
Mean · log10 ng/mg
Pharmacokinetics: End Period Tenofovir-Diphosphate (TFV-DP) Concentrations (log10 ng/mg) in Rectal Tissue
log10 ng/mgProduct 1Product 2Product 3
Pharmacokinetics: End Period Tenofovir-Diphosphate (TFV-DP) Concentrations (log10 ng/mg) in Rectal Tissue1.52 ± 0.502.06 ± 0.521.54 ± 0.92
Statistical analysis
  • Product 1 vs Product 2 · Mixed Models Analysis · p = <0.001 · Slope: 0.54 · 95% CI 0.35 to 0.72
  • Product 1 vs Product 3 · Mixed Models Analysis · p = 0.92 · Slope: 0.01 · 95% CI -0.28 to 0.31
SecondaryAdherence: Percentage of Prescribed Doses Taken Orally or Administered Rectally in an 8-week Period

Compare percentage of prescribed doses taken orally or administered rectally in an 8-week period based on the Final Converged Rates. Final Converged Rates were measured first via self-report through Short Message Service (SMS). The clinic staff also reported the most likely number of doses taken. Finally, the MTN Behavioral Research Working Group (BRWG) provided the final estimate of the number of doses taken for each participant for each period based on self-report, staff estimates and PK testing results. Note that these final judgement data are missing if PK results are missing.

Time frame:
27 weeks (three 8-week product use periods with 1-week washout periods between them)
Reported as:
Count of participants · Participants
Adherence: Percentage of Prescribed Doses Taken Orally or Administered Rectally in an 8-week Period
ParticipantsProduct 1Product 2Product 3
Less Than 80%123113
At or Greater than 80%173153170
Statistical analysis
  • Product 1 vs Product 2 · Generalized Estimating Equations (GEE) · p = 0.0005 · Odds ratio (or): 0.35 · 95% CI 0.19 to 0.63Oral regimen is the reference group.
  • Product 1 vs Product 3 · Generalized Estimating Equations (GEE) · p = 0.74 · Odds ratio (or): 0.89 · 95% CI 0.43 to 1.81Oral regimen is the reference group.
Other pre-specifiedPharmacodynamics

To characterize pharmacodynamic responses following oral and rectal exposure to antiretroviral drugs

Time frame:
27 weeks (three 8-week product use periods with 1-week washout periods between them)

Results for this outcome have not been posted.

Other pre-specifiedMucosal Immunity

To characterize changes in mucosal immunity between baseline and the end of the daily FTC/TDF and TFV RG 1% gel product use

Time frame:
27 weeks (three 8-week product use periods with 1-week washout periods between them)

Results for this outcome have not been posted.

Other pre-specifiedCorrelation Between PK and Adherence

To assess correlation of PK with adherence measures

Time frame:
27 weeks (three 8-week product use periods with 1-week washout periods between them)

Results for this outcome have not been posted.

Other pre-specifiedFactors Associated With Adherence

To identify factors associated with product adherence and whether they differ by product used (FTC/TDF or TFV RG 1% gel) or regimen (daily use or RAI-associated use)

Time frame:
27 weeks (three 8-week product use periods with 1-week washout periods between them)

Results for this outcome have not been posted.

Other pre-specifiedSexual Activity and Condom Use

To examine whether sexual activity or condom use varies by product used

Time frame:
27 weeks (three 8-week product use periods with 1-week washout periods between them)

Results for this outcome have not been posted.

Other pre-specifiedProduct Sharing

To determine the level of sharing of study products with non-participants and to assess with whom products are shared

Time frame:
27 weeks (three 8-week product use periods with 1-week washout periods between them)

Results for this outcome have not been posted.

Other pre-specifiedProblem Practices

To determine the prevalence of behavioral practices associated with anal intercourse that may affect microbicide use

Time frame:
27 weeks (three 8-week product use periods with 1-week washout periods between them)

Results for this outcome have not been posted.

Adverse events

Collected over 27 weeks (three 8-week product use periods with 1-week washout periods between them). Non-serious events are listed at a 3% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Product 1—1/192 (0.5%)85/192 (44.3%)
Product 2—2/192 (1%)103/192 (53.6%)
Product 3—0/191 (0%)87/191 (45.5%)
Most frequent serious events
Most frequent serious events
EventProduct 1Product 2Product 3
HospitalisationSurgical and medical procedures0/1921/1920/191
AppendicitisInfections and infestations0/1921/1920/191
Suicide attemptPsychiatric disorders1/1920/1920/191
Most frequent other events
Showing 10 of 23
Most frequent other events
EventProduct 1Product 2Product 3
FlatulenceGastrointestinal disorders12/19223/19214/191
DiarrhoeaGastrointestinal disorders14/19222/19215/191
NasopharyngitisInfections and infestations12/19210/19220/191
HeadacheNervous system disorders17/1929/1927/191
Defaecation urgencyGastrointestinal disorders2/19216/19211/191
NauseaGastrointestinal disorders15/1924/1922/191
Proctitis chlamydialInfections and infestations9/1928/19213/191
Upper respiratory tract infectionInfections and infestations5/19210/19211/191
Viral upper respiratory tract infectionInfections and infestations7/19211/19210/191
Rectal haemorrhageGastrointestinal disorders4/1929/1925/191

Baseline characteristics

Includes all participants enrolled.

Age, Continuous
Age, Continuous(years)Group 1Group 2Group 3Group 4Group 5Group 6Total
Mean30.9 ± 8.530.4 ± 10.632.4 ± 9.229.6 ± 8.932.2 ± 10.631.4 ± 7.831.1 ± 9.3
Age, Customized
Age, Customized(participants)Group 1Group 2Group 3Group 4Group 5Group 6Total
Under 2021212210
20-24776127544
25-29711667643
30-34646771040
35-3964222420
40-4443433219
45-4900422311
50+1211308
Sex/Gender, Customized
Sex/Gender, Customized(participants)Group 1Group 2Group 3Group 4Group 5Group 6Total
Man212122272624141
Woman0011114
Transgender/Transwoman46233119
Other54633627
Refuse to answer2100003
Hispanic Origin
Hispanic Origin(participants)Group 1Group 2Group 3Group 4Group 5Group 6Total
Yes1098812855
No232323262124140
Highest Level of Education
Highest Level of Education(participants)Group 1Group 2Group 3Group 4Group 5Group 6Total
no schooling0000000
primary school, not complete0001001
primary school, complete0010012
secondary school, not complete2111319
secondary school, complete25644627
attended college or university292623282624156
Sexual Orientation (CASI)
Sexual Orientation (CASI)(participants)Group 1Group 2Group 3Group 4Group 5Group 6Total
Gay/Homosexual272627322831171
Bisexual33303113
Straight/Heterosexual0111003
Other1101205
Refuse to answer1100002
Nationality
Nationality(participants)Group 1Group 2Group 3Group 4Group 5Group 6Total
Puerto Rico1111217
Peru76667638
South Africa33333318
Thailand99999954
U.S.A.13131215121378
Race - Puerto Rico
Race - Puerto Rico(participants)Group 1Group 2Group 3Group 4Group 5Group 6Total
White0000202
Asian0000000
Mixed0100012
Black0011002
Indigenous0000000
Other1000001

4 further baseline measures are reported on the registry.

07

Study locations

8 sites
  • HIV Research Section, San Francisco - Department of Public Health
    San Francisco, California 94102, United States
  • The Fenway Institute/Fenway Community Health
    Boston, Massachusetts 02115, United States
  • University of Pittsburgh Medical Center (UPMC)
    Pittsburgh, Pennsylvania 15213, United States
  • Asociacion Civil Impacta Salud y Educacion (IMPACTA)
    Lima, Peru
  • University of Puerto Rico Medical Sciences Campus - Maternal Infant Studies Center (CEMI)
    San Juan, 00936-5067, Puerto Rico
  • Desmond Tutu HIV Foundation
    Cape Town, South Africa
  • Research Institute for Health Sciences - Chiang Mai University
    Chiang Mai, 50202, Thailand
  • Thailand MOPH - US CDC Collaboration (TUC)
    Nonthaburi, 11000, Thailand
08

References and documents

Publications

  • Cranston RD, Lama JR, Richardson BA, Carballo-Dieguez A, Kunjara Na Ayudhya RP, Liu K, Patterson KB, Leu CS, Galaska B, Jacobson CE, Parikh UM, Marzinke MA, Hendrix CW, Johnson S, Piper JM, Grossman C, Ho KS, Lucas J, Pickett J, Bekker LG, Chariyalertsak S, Chitwarakorn A, Gonzales P, Holtz TH, Liu AY, Mayer KH, Zorrilla C, Schwartz JL, Rooney J, McGowan I; MTN-017 Protocol Team. MTN-017: A Rectal Phase 2 Extended Safety and Acceptability Study of Tenofovir Reduced-Glycerin 1% Gel. Clin Infect Dis. 2017 Mar 1;64(5):614-620. doi: 10.1093/cid/ciw832. PubMed 27986684 ↗
  • Carballo-Dieguez A, Balan IC, Brown W 3rd, Giguere R, Dolezal C, Leu CS, Marzinke MA, Hendrix CW, Piper JM, Richardson BA, Grossman C, Johnson S, Gomez K, Horn S, Kunjara Na Ayudhya RP, Patterson K, Jacobson C, Bekker LG, Chariyalertsak S, Chitwarakorn A, Gonzales P, Holtz TH, Liu A, Mayer KH, Zorrilla C, Lama J, McGowan I, Cranston RD. High levels of adherence to a rectal microbicide gel and to oral Pre-Exposure Prophylaxis (PrEP) achieved in MTN-017 among men who have sex with men (MSM) and transgender women. PLoS One. 2017 Jul 27;12(7):e0181607. doi: 10.1371/journal.pone.0181607. eCollection 2017. PubMed 28750059 ↗
  • Giguere R, Brown W III, Balan IC, Dolezal C, Ho T, Sheinfil A, Ibitoye M, Lama JR, McGowan I, Cranston RD, Carballo-Dieguez A. Are participants concerned about privacy and security when using short message service to report product adherence in a rectal microbicide trial? J Am Med Inform Assoc. 2018 Apr 1;25(4):393-400. doi: 10.1093/jamia/ocx081. PubMed 29025127 ↗
  • Carballo-Dieguez A, Giguere R, Dolezal C, Leu CS, Balan IC, Brown W 3rd, Rael C, Richardson BA, Piper JM, Bekker LG, Chariyalertsak S, Chitwarakorn A, Gonzales P, Holtz TH, Liu A, Mayer KH, Zorrilla CD, Lama JR, McGowan I, Cranston RD; MTN-017 Protocol Team. Preference of Oral Tenofovir Disoproxil Fumarate/Emtricitabine Versus Rectal Tenofovir Reduced-Glycerin 1% Gel Regimens for HIV Prevention Among Cisgender Men and Transgender Women Who Engage in Receptive Anal Intercourse with Men. AIDS Behav. 2017 Dec;21(12):3336-3345. doi: 10.1007/s10461-017-1969-1. PubMed 29119473 ↗
  • Giguere R, Rael CT, Sheinfil A, Balan IC, Brown W 3rd, Ho T, Dolezal C, Leu CS, Liu A, Mayer KH, Lama JR, McGowan I, Carballo-Dieguez A, Cranston RD; MTN-017 Protocol Team. Factors Supporting and Hindering Adherence to Rectal Microbicide Gel Use with Receptive Anal Intercourse in a Phase 2 Trial. AIDS Behav. 2018 Feb;22(2):388-401. doi: 10.1007/s10461-017-1890-7. PubMed 28825142 ↗
  • Brown W 3rd, Giguere R, Sheinfil A, Ibitoye M, Balan I, Ho T, Brown B, Quispe L, Sukwicha W, Lama JR, Carballo-Dieguez A, Cranston RD. Challenges and solutions implementing an SMS text message-based survey CASI and adherence reminders in an international biomedical HIV PrEP study (MTN 017). J Biomed Inform. 2018 Apr;80:78-86. doi: 10.1016/j.jbi.2018.02.018. Epub 2018 Mar 6. PubMed 29501908 ↗
  • Cranston RD, Carballo-Dieguez A, Gundacker H, Richardson BA, Giguere R, Dolezal C, Siegel A, KunjaraNaAyudhya RP, Gomez K, Piper JM, Lama JR, McGowan I; MTN-017 Protocol Team. Prevalence and determinants of anal human papillomavirus infection in men who have sex with men and transgender women. Int J STD AIDS. 2019 Feb;30(2):154-162. doi: 10.1177/0956462418797864. Epub 2018 Oct 18. PubMed 30336747 ↗
  • Leu CS, Giguere R, Bauermeister JA, Dolezal C, Brown W 3rd, Balan IC, Richardson BA, Piper JM, Lama JR, Cranston RD, Carballo-Dieguez A. Trajectory of use over time of an oral tablet and a rectal gel for HIV prevention among transgender women and men who have sex with men. AIDS Care. 2019 Mar;31(3):379-387. doi: 10.1080/09540121.2018.1533223. Epub 2018 Oct 14. PubMed 30318905 ↗
  • Liu AY, Norwood A, Gundacker H, Carballo-Dieguez A, Johnson S, Patterson K, Bekker LG, Chariyalertsak S, Chitwarakorn A, Gonzales P, Holtz TH, Mayer KH, Zorrilla C, Buchbinder S, Piper JM, Lama JR, Cranston RD. Brief Report: Routine Use of Oral PrEP in a Phase 2 Rectal Microbicide Study of Tenofovir Reduced-Glycerin 1% Gel (MTN-017). J Acquir Immune Defic Syndr. 2019 Aug 15;81(5):516-520. doi: 10.1097/QAI.0000000000002066. PubMed 31299013 ↗
  • Balan IC, Giguere R, Brown W 3rd, Carballo-Dieguez A, Horn S, Hendrix CW, Marzinke MA, Ayudhya RPKN, Patterson K, Piper JM, McGowan I, Lama JR, Cranston RD; MTN-017 Protocol Team. Brief Participant-Centered Convergence Interviews Integrate Self-Reports, Product Returns, and Pharmacokinetic Results to Improve Adherence Measurement in MTN-017. AIDS Behav. 2018 Mar;22(3):986-995. doi: 10.1007/s10461-017-1955-7. PubMed 29076032 ↗
  • McGowan IM, Kunjara Na Ayudhya RP, Brand RM, Marzinke MA, Hendrix CW, Johnson S, Piper J, Holtz TH, Curlin ME, Chitwarakorn A, Raengsakulrach B, Doncel G, Schwartz JL, Rooney JF, Cranston RD. An Open-Label Pharmacokinetic and Pharmacodynamic Assessment of Tenofovir Gel and Oral Emtricitabine/Tenofovir Disoproxil Fumarate. AIDS Res Hum Retroviruses. 2022 Apr;38(4):279-287. doi: 10.1089/AID.2021.0115. Epub 2021 Oct 29. PubMed 34541872 ↗
09

Registry details

Key details

Study ID
NCT01687218
Lead sponsor
CONRAD
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Mental Health (NIMH), National Institutes of Health (NIH)
Responsible party
Sponsor
First posted
Sep 18, 2012
Start date
Sep 25, 2013
Primary completion
May 26, 2015
Completion
May 26, 2015
Results posted
Feb 1, 2017
Last update
Jun 24, 2021

Study contacts

Ross D. Cranston, MD, FRCP
study chair · University of Pittsburgh Medical Center (UPMC)
Javier R. Lama, MD, MPH
study chair · Asociacion Civil Impacta Salud y Educacion (IMPACTA)

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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