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

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ClinicalTrials.gov Identifier: NCT01687218
Recruitment Status : Completed
First Posted : September 18, 2012
Results First Posted : February 1, 2017
Last Update Posted : March 30, 2017
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Mental Health (NIMH)
National Institutes of Health (NIH)
Information provided by (Responsible Party):
CONRAD

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Condition HIV
Interventions 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)
Enrollment 195

Recruitment Details 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.
Pre-assignment Details 349 persons were screened and 154 were excluded for various reasons. The study enrolled 195 participants, 187 of whom are evaluable. Evaluable participants are those participants who were enrolled and not replaced, or were the final enrolled replacement participant for another enrolled participant who met the criteria for replacement.
Arm/Group Title Group 1 Group 2 Group 3 Group 4 Group 5 Group 6
Hide Arm/Group Description

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)

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

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

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

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)

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

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

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

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)

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

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

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

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)

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

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

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

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)

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

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

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

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)

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

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

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

Period Title: Overall Study
Started 33 32 31 34 33 32
Completed 30 29 30 32 32 32
Not Completed 3 3 1 2 1 0
Reason Not Completed
Withdrawal by Subject             2             3             0             1             1             0
Relocated, no follow-up planned             1             0             1             1             0             0
Arm/Group Title Group 1 Group 2 Group 3 Group 4 Group 5 Group 6 Total
Hide Arm/Group Description

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)

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

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

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

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)

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

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

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

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)

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

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

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

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)

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

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

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

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)

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

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

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

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)

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

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

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

Total of all reporting groups
Overall Number of Baseline Participants 33 32 31 34 33 32 195
Hide Baseline Analysis Population Description
Includes all participants enrolled.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 33 participants 32 participants 31 participants 34 participants 33 participants 32 participants 195 participants
30.9  (8.5) 30.4  (10.6) 32.4  (9.2) 29.6  (8.9) 32.2  (10.6) 31.4  (7.8) 31.1  (9.3)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 32 participants 31 participants 34 participants 33 participants 32 participants 195 participants
Under 20 2 1 2 1 2 2 10
20-24 7 7 6 12 7 5 44
25-29 7 11 6 6 7 6 43
30-34 6 4 6 7 7 10 40
35-39 6 4 2 2 2 4 20
40-44 4 3 4 3 3 2 19
45-49 0 0 4 2 2 3 11
50+ 1 2 1 1 3 0 8
Sex/Gender, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 32 participants 31 participants 34 participants 33 participants 32 participants 195 participants
Man 21 21 22 27 26 24 141
Woman 0 0 1 1 1 1 4
Transgender/Transwoman 4 6 2 3 3 1 19
Other 5 4 6 3 3 6 27
Refuse to answer 2 1 0 0 0 0 3
[1]
Measure Description: One participant from Peru did not complete a baseline CASI.
Hispanic Origin  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 32 participants 31 participants 34 participants 33 participants 32 participants 195 participants
Yes 10 9 8 8 12 8 55
No 23 23 23 26 21 24 140
Highest Level of Education  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 32 participants 31 participants 34 participants 33 participants 32 participants 195 participants
no schooling 0 0 0 0 0 0 0
primary school, not complete 0 0 0 1 0 0 1
primary school, complete 0 0 1 0 0 1 2
secondary school, not complete 2 1 1 1 3 1 9
secondary school, complete 2 5 6 4 4 6 27
attended college or university 29 26 23 28 26 24 156
Sexual Orientation (CASI)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 32 participants 31 participants 34 participants 33 participants 32 participants 195 participants
Gay/Homosexual 27 26 27 32 28 31 171
Bisexual 3 3 3 0 3 1 13
Straight/Heterosexual 0 1 1 1 0 0 3
Other 1 1 0 1 2 0 5
Refuse to answer 1 1 0 0 0 0 2
[1]
Measure Description: One participant from Peru did not complete a baseline CASI.
Nationality   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 32 participants 31 participants 34 participants 33 participants 32 participants 195 participants
Puerto Rico 1 1 1 1 2 1 7
Peru 7 6 6 6 7 6 38
South Africa 3 3 3 3 3 3 18
Thailand 9 9 9 9 9 9 54
U.S.A. 13 13 12 15 12 13 78
[1]
Measure Description: Country in which the site clinic resides.
Race - Puerto Rico  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 32 participants 31 participants 34 participants 33 participants 32 participants 195 participants
White 0 0 0 0 2 0 2
Asian 0 0 0 0 0 0 0
Mixed 0 1 0 0 0 1 2
Black 0 0 1 1 0 0 2
Indigenous 0 0 0 0 0 0 0
Other 1 0 0 0 0 0 1
Race - Peru  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 32 participants 31 participants 34 participants 33 participants 32 participants 195 participants
White 0 0 0 1 0 0 1
Asian 0 0 0 0 0 0 0
Mixed 6 3 3 4 3 5 24
Black 0 0 0 0 0 0 0
Indigenous 1 3 3 1 4 1 13
Other 0 0 0 0 0 0 0
Race - South Africa  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 32 participants 31 participants 34 participants 33 participants 32 participants 195 participants
Other African tribe 0 0 0 1 0 1 2
White 0 0 0 0 0 0 0
Zulu 0 0 0 0 0 0 0
Xhosa 3 2 3 2 3 1 14
Indian 0 0 0 0 0 0 0
Colored 0 0 0 0 0 1 1
Other 0 1 0 0 0 0 1
Race - Thailand  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 32 participants 31 participants 34 participants 33 participants 32 participants 195 participants
Indian 0 0 0 0 0 0 0
Mixed 0 0 0 0 0 0 0
Thai 9 9 9 9 9 9 54
Chinese 0 0 0 0 0 0 0
Other 0 0 0 0 0 0 0
Race - U.S.A.  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 32 participants 31 participants 34 participants 33 participants 32 participants 195 participants
White 12 11 10 12 6 10 61
Asian 0 0 0 0 2 2 4
Mixed 0 0 0 0 2 0 2
Black/African-American 0 0 0 3 0 0 3
American Indian/Alaska Native 0 0 0 0 0 0 0
Native-Hawaiian or other Pacific Islander 0 0 0 0 0 0 0
Other 1 2 2 0 2 1 8
1.Primary Outcome
Title Safety: Grade 2 or Higher Adverse Events
Hide Description 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Among the 187 evaluable participants. One participant was terminated before the Initiate Period visit of his/her Period 3 (Oral Tablet regimen period). Thus, this participant is removed from the analysis of the oral period regimen.
Arm/Group Title Product 1 Product 2 Product 3
Hide Arm/Group Description:
Oral (Daily FTC/TDF)
Rectal (Daily TFV RG 1% gel)
Rectal (RAI-associated TFV RG 1% gel)
Overall Number of Participants Analyzed 186 187 187
Measure Type: Number
Unit of Measure: participants
64 61 56
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Product 1, Product 2
Comments Since some participants have more than one safety event per period of treatment regimen, a Generalized Estimating Equation (GEE) model with a Poisson (log) link, exchangeable correlation structure, and robust standard errors were used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.88
Comments [Not Specified]
Method Generalized Estimating Equation (GEE)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.73 to 1.44
Estimation Comments It 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.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Product 1, Product 3
Comments Since some participants have more than one safety event per period of treatment regimen, a Generalized Estimating Equation (GEE) model with a Poisson (log) link, exchangeable correlation structure, and robust standard errors were used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.43
Comments [Not Specified]
Method Generalized Estimating Equation (GEE)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.64 to 1.21
Estimation Comments It 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.
2.Primary Outcome
Title Acceptability: Participant Self-report of Liking the Product. H1-Overall How do You Feel About the Product You Used Recently?
Hide Description 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All primary analyses are based on the data from evaluable participants. Evaluable participants are those participants who were enrolled and not replaced, or were the final enrolled replacement participant for another enrolled participant who met the criteria for replacement.
Arm/Group Title Product 1 Product 2 Product 3
Hide Arm/Group Description:
Oral (Daily FTC/TDF)
Rectal (Daily TFV RG 1% gel)
Rectal (RAI-associated TFV RG 1% gel)
Overall Number of Participants Analyzed 179 181 183
Measure Type: Number
Unit of Measure: participants
Disliked Very Much/A Little 16 47 38
Liked Very Much/A Little 163 134 145
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Product 1, Product 2
Comments Generalized Estimating Equation (GEE) models with a binomial (logit) link, an exchangeable correlation structure and robust errors and with treatment regimen and period as independent variables were used to compare the three treatment regimens for the acceptability endpoints. The oral arm and period 1 were used as the reference group in each of the models.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Generalized Estimating Equation (GEE)
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.28
Confidence Interval (2-Sided) 95%
0.15 to 0.50
Estimation Comments Oral regimen is the reference group.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Product 1, Product 3
Comments Generalized Estimating Equation (GEE) models with a binomial (logit) link, an exchangeable correlation structure and robust errors and with treatment regimen and period as independent variables were used to compare the three treatment regimens for the acceptability endpoints. The oral arm and period 1 were used as the reference group in each of the models.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Generalized Estimating Equation (GEE)
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.37
Confidence Interval (2-Sided) 95%
0.20 to 0.70
Estimation Comments Oral regimen is the reference group.
3.Primary Outcome
Title Acceptability: Participant Self-report of Ease of Use. I1-Overall How Easy or Difficult Was it to Use the Product?
Hide Description 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All primary analyses are based on the data from evaluable participants. Evaluable participants are those participants who were enrolled and not replaced, or were the final enrolled replacement participant for another enrolled participant who met the criteria for replacement.
Arm/Group Title Product 1 Product 2 Product 3
Hide Arm/Group Description:
Oral (Daily FTC/TDF)
Rectal (Daily TFV RG 1% gel)
Rectal (RAI-associated TFV RG 1% gel)
Overall Number of Participants Analyzed 183 184 183
Measure Type: Number
Unit of Measure: participants
Very Difficult/Difficult 14 24 18
Very Easy/Easy 169 160 165
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Product 1, Product 2
Comments Generalized Estimating Equation (GEE) models with a binomial (logit) link, an exchangeable correlation structure and robust errors and with treatment regimen and period as independent variables were used to compare the three treatment regimens for the acceptability endpoints. The oral arm and period 1 were used as the reference group in each of the models.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.08
Comments [Not Specified]
Method Generalized Estimating Equation (GEE)
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.56
Confidence Interval (2-Sided) 95%
0.29 to 1.08
Estimation Comments Oral regimen is the reference group.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Product 1, Product 3
Comments Generalized Estimating Equation (GEE) models with a binomial (logit) link, an exchangeable correlation structure and robust errors and with treatment regimen and period as independent variables were used to compare the three treatment regimens for the acceptability endpoints. The oral arm and period 1 were used as the reference group in each of the models.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.46
Comments [Not Specified]
Method Generalized Estimating Equation (GEE)
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
0.37 to 1.56
Estimation Comments Oral regimen is the reference group.
4.Primary Outcome
Title 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?
Hide Description 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All primary analyses are based on the data from evaluable participants. Evaluable participants are those participants who were enrolled and not replaced, or were the final enrolled replacement participant for another enrolled participant who met the criteria for replacement.
Arm/Group Title Product 1 Product 2 Product 3
Hide Arm/Group Description:
Oral (Daily FTC/TDF)
Rectal (Daily TFV RG 1% gel)
Rectal (RAI-associated TFV RG 1% gel)
Overall Number of Participants Analyzed 183 184 176
Measure Type: Number
Unit of Measure: participants
Very Unlikely/Unlikely 24 52 31
Very Likely/Likely 159 132 145
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Product 1, Product 2
Comments Generalized Estimating Equation (GEE) models with a binomial (logit) link, an exchangeable correlation structure and robust errors and with treatment regimen and period as independent variables were used to compare the three treatment regimens for the acceptability endpoints. The oral arm and period 1 were used as the reference group in each of the models.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Generalized Estimating Equation (GEE)
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.38
Confidence Interval (2-Sided) 95%
0.22 to 0.65
Estimation Comments Oral regimen is the reference group.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Product 1, Product 3
Comments Generalized Estimating Equation (GEE) models with a binomial (logit) link, an exchangeable correlation structure and robust errors and with treatment regimen and period as independent variables were used to compare the three treatment regimens for the acceptability endpoints. The oral arm and period 1 were used as the reference group in each of the models.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.23
Comments [Not Specified]
Method Generalized Estimating Equation (GEE)
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.39 to 1.25
Estimation Comments Oral regimen is the reference group.
5.Secondary Outcome
Title Pharmacokinetics
Hide Description To compare systemic and local PK among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel
Time Frame 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Adherence
Hide Description To evaluate and compare adherence to daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel. The Behavioral Research Working Group provided the final adherence estimate of the percentage of prescribed doses taken for each participant for each period based on participant self-report, staff estimates and PK testing results.
Time Frame 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All secondary analyses are based on the data from evaluable participants
Arm/Group Title Product 1 Product 2 Product 3
Hide Arm/Group Description:
Oral (Daily FTC/TDF)
Rectal (Daily TFV RG 1% gel)
Rectal (RAI-associated TFV RG 1% gel)
Overall Number of Participants Analyzed 185 184 183
Measure Type: Number
Unit of Measure: participants
Less Than 80% 12 31 13
At or Greater than 80% 173 153 170
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Product 1, Product 2
Comments Generalized Estimating Equation (GEE) models with a binomial (logit) link, an exchangeable correlation structure and robust errors and with treatment regimen and period as independent variables was used to compare the three treatment regimens for the acceptability endpoints. Because the distribution of the adherence percentages were skewed, we did not use a linear mixed effects model as originally planned. Instead, we dichotomized the adherence percentage into<80% adherence versus>80% adherence.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Generalized Estimating Equation (GEE)
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.35
Confidence Interval (2-Sided) 95%
0.19 to 0.63
Estimation Comments Oral regimen is the reference group.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Product 1, Product 3
Comments Generalized Estimating Equation (GEE) models with a binomial (logit) link, an exchangeable correlation structure and robust errors and with treatment regimen and period as independent variables was used to compare the three treatment regimens for the acceptability endpoints. Because the distribution of the adherence percentages were skewed, we did not use a linear mixed effects model as originally planned. Instead, we dichotomized the adherence percentage into<80% adherence versus>80% adherence.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.74
Comments [Not Specified]
Method Generalized Estimating Equation (GEE)
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.43 to 1.81
Estimation Comments Oral regimen is the reference group.
7.Other Pre-specified Outcome
Title Pharmacodynamics
Hide Description 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)
Outcome Measure Data Not Reported
8.Other Pre-specified Outcome
Title Mucosal Immunity
Hide Description 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)
Outcome Measure Data Not Reported
9.Other Pre-specified Outcome
Title Correlation Between PK and Adherence
Hide Description 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)
Outcome Measure Data Not Reported
10.Other Pre-specified Outcome
Title Factors Associated With Adherence
Hide Description 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)
Outcome Measure Data Not Reported
11.Other Pre-specified Outcome
Title Sexual Activity and Condom Use
Hide Description 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)
Outcome Measure Data Not Reported
12.Other Pre-specified Outcome
Title Product Sharing
Hide Description 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)
Outcome Measure Data Not Reported
13.Other Pre-specified Outcome
Title Problem Practices
Hide Description 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)
Outcome Measure Data Not Reported
Time Frame 27 weeks (three 8-week product use periods with 1-week washout periods between them)
Adverse Event Reporting Description AEs are reported throughout follow-up. AEs are assigned to a regimen based on the reported or derived onset date being on or after the first visit of the regimen and before the start of the next regimen.
 
Arm/Group Title Product 1 Product 2 Product 3
Hide Arm/Group Description Oral (Daily FTC/TDF) Rectal (Daily TFV RG 1% gel) Rectal (RAI-associated TFV RG 1% gel)
All-Cause Mortality
Product 1 Product 2 Product 3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Product 1 Product 2 Product 3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/192 (0.52%)   2/192 (1.04%)   0/191 (0.00%) 
Infections and infestations       
Appendicitis  1  0/192 (0.00%)  1/192 (0.52%)  0/191 (0.00%) 
Psychiatric disorders       
Suicide attempt  1  1/192 (0.52%)  0/192 (0.00%)  0/191 (0.00%) 
Surgical and medical procedures       
Hospitalisation  1  0/192 (0.00%)  1/192 (0.52%)  0/191 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Product 1 Product 2 Product 3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   85/192 (44.27%)   103/192 (53.65%)   87/191 (45.55%) 
Gastrointestinal disorders       
Abdominal distension  1  4/192 (2.08%)  2/192 (1.04%)  6/191 (3.14%) 
Abdominal pain  1  8/192 (4.17%)  5/192 (2.60%)  7/191 (3.66%) 
Anal fissure  1  1/192 (0.52%)  7/192 (3.65%)  7/191 (3.66%) 
Anorectal discomfort  1  0/192 (0.00%)  6/192 (3.13%)  3/191 (1.57%) 
Defaecation urgency  1  2/192 (1.04%)  16/192 (8.33%)  11/191 (5.76%) 
Diarrhoea  1  14/192 (7.29%)  22/192 (11.46%)  15/191 (7.85%) 
Dyspepsia  1  7/192 (3.65%)  3/192 (1.56%)  0/191 (0.00%) 
Flatulence  1  12/192 (6.25%)  23/192 (11.98%)  14/191 (7.33%) 
Gastrointestinal mucosa hyperaemia  1  1/192 (0.52%)  6/192 (3.13%)  2/191 (1.05%) 
Nausea  1  15/192 (7.81%)  4/192 (2.08%)  2/191 (1.05%) 
Proctalgia  1  3/192 (1.56%)  7/192 (3.65%)  4/191 (2.09%) 
Rectal haemorrhage  1  4/192 (2.08%)  9/192 (4.69%)  5/191 (2.62%) 
Rectal tenesmus  1  0/192 (0.00%)  7/192 (3.65%)  3/191 (1.57%) 
Vomiting  1  6/192 (3.13%)  4/192 (2.08%)  1/191 (0.52%) 
General disorders       
Fatigue  1  6/192 (3.13%)  1/192 (0.52%)  2/191 (1.05%) 
Infections and infestations       
Nasopharyngitis  1  12/192 (6.25%)  10/192 (5.21%)  20/191 (10.47%) 
Proctitis chlamydial  1  9/192 (4.69%)  8/192 (4.17%)  13/191 (6.81%) 
Proctitis gonococcal  1  5/192 (2.60%)  3/192 (1.56%)  6/191 (3.14%) 
Upper respiratory tract infection  1  5/192 (2.60%)  10/192 (5.21%)  11/191 (5.76%) 
Viral upper respiratory tract infection  1  7/192 (3.65%)  11/192 (5.73%)  10/191 (5.24%) 
Nervous system disorders       
Dizziness  1  9/192 (4.69%)  3/192 (1.56%)  6/191 (3.14%) 
Headache  1  17/192 (8.85%)  9/192 (4.69%)  7/191 (3.66%) 
Respiratory, thoracic and mediastinal disorders       
Oropharyngeal pain  1  3/192 (1.56%)  6/192 (3.13%)  5/191 (2.62%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Ross D. Cranston, MD, FRCP
Organization: Division of Infectious Diseases - UPMC
Phone: 412-383-2054
Responsible Party: CONRAD
ClinicalTrials.gov Identifier: NCT01687218     History of Changes
Other Study ID Numbers: MTN-017
5UM1AI068633 ( U.S. NIH Grant/Contract )
11857 ( Other Identifier: DAIDS protocol # )
First Submitted: August 27, 2012
First Posted: September 18, 2012
Results First Submitted: December 7, 2016
Results First Posted: February 1, 2017
Last Update Posted: March 30, 2017