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

NCT01687218 | Completed Phase 2 Results DMC

• 3 other identifiers: MTN-0175UM1AI06863311857
• Study Type: interventional
• Target: 195
• Locations: 5 countries
• Sites: 8

Brief 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.

Conditions

HIV

Outcome Measures

Primary Outcomes (4)

• 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).

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

• 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.

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

• 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.

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

• 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.

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

Secondary Outcomes (8)

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

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

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

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

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

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

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

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

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

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

Other Outcomes (7)

• Pharmacodynamics

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

• Mucosal Immunity

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

• Correlation Between PK and Adherence

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

Study Arms (6)

Group 1

ACTIVE COMPARATOR

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)

Group 2

ACTIVE COMPARATOR

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)

Group 3

ACTIVE COMPARATOR

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)

Group 4

ACTIVE COMPARATOR

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)

Group 5

ACTIVE COMPARATOR

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)

Group 6

ACTIVE COMPARATOR

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

Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet) DRUG

Group 1; Group 2; Group 3; Group 4; Group 5; Group 6

Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel) DRUG

Group 1; Group 2; Group 3; Group 4; Group 5; Group 6

Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel) DRUG

Group 1; Group 2; Group 3; Group 4; Group 5; Group 6

Eligibility Criteria

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

You may qualify if:

• Male or transgender female \> age of 18 at Screening
• Able and willing to provide written informed consent
• HIV-1 uninfected at Screening and Enrollment
• Able and willing to provide adequate locator information, as defined in site SOP
• Available to return for all study visits, barring unforeseen circumstances and willing to comply with study participation requirements
• In general good health at Screening and Enrollment, as determined by the site IoR or designee
• Per participant report, a history of consensual RAI at least once in the past 3 months
• 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.
• Willing to use study-provided condoms for the duration of the study for penetrative intercourse
• 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)
• 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.

You may not qualify if:

• 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
• History of inflammatory bowel disease as reported by participant history
• 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
• Known allergy to methylparaben and/or propylparaben

Sponsors & Collaborators

• CONRAD: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• National Institute of Mental Health (NIMH): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (8)

HIV Research Section, San Francisco - Department of Public Health

San Francisco, California, 94102, United States

Location

The Fenway Institute/Fenway Community Health

Boston, Massachusetts, 02115, United States

Location

University of Pittsburgh Medical Center (UPMC)

Pittsburgh, Pennsylvania, 15213, United States

Location

Asociacion Civil Impacta Salud y Educacion (IMPACTA)

Lima, Peru

Location

University of Puerto Rico Medical Sciences Campus - Maternal Infant Studies Center (CEMI)

San Juan, 00936-5067, Puerto Rico

Location

Desmond Tutu HIV Foundation

Cape Town, South Africa

Location

Research Institute for Health Sciences - Chiang Mai University

Chiang Mai, 50202, Thailand

Location

Thailand MOPH - US CDC Collaboration (TUC)

Nonthaburi, 11000, Thailand

Location

Related Publications (11)

• 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.

  PMID: 27986684 RESULT

• 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.

  PMID: 28750059 RESULT

• 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.

  PMID: 29025127 RESULT

• 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.

  PMID: 29119473 RESULT

• 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.

  PMID: 28825142 RESULT

• 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.

  PMID: 29501908 RESULT

• 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.

  PMID: 30336747 RESULT

• 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.

  PMID: 30318905 RESULT

• 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.

  PMID: 31299013 RESULT

• 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.

  PMID: 29076032 RESULT

• 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.

  PMID: 34541872 DERIVED

MeSH Terms

Interventions

Tenofovir; Gels

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Ross D. Cranston, MD, FRCP
• Organization: Division of Infectious Diseases - UPMC

rdc27@pitt.edu

412-383-2054

Study Officials

• Ross D. Cranston, MD, FRCP

  University of Pittsburgh Medical Center (UPMC)

  STUDY CHAIR

• Javier R. Lama, MD, MPH

  Asociacion Civil Impacta Salud y Educacion (IMPACTA)

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2012
• First Posted: September 18, 2012
• Study Start: September 25, 2013
• Primary Completion: May 26, 2015
• Study Completion: May 26, 2015
• Last Updated: June 24, 2021
• Results First Posted: February 1, 2017

Record last verified: 2021-06

Locations

PR (1); ZA (1); TH (2); US (3); PE (1)