Trial Outcomes & Findings for Comparative Safety Study of Two Vaginal Applicators With Tenofovir (NCT NCT01283555)

NCT ID: NCT01283555

Last Updated: 2012-07-16

Results Overview

Comparison of colposcopic findings between baseline visits and after one week of twice-daily application of Tenofovir 1% gel with either a user-filled or prefilled applicator

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 25 participants
• Primary outcome timeframe: 7 days
• Results posted on: 2012-07-16

Participant Flow

Recruitment began on 26 January 2011 and ended on 10 March 2011. Recruitment was done at Clinica Profamilia, Santo Domingo, Dominican Republic. Healthy women, 18 to 50 years of age (inclusive), who attended the clinic for health care, who were not at risk for pregnancy, and at low risk of sexually transmitted infection were informed of the study.

25 were enrolled in this study which used a cross-over design. Participants were randomized to order of applicator use.

Participant milestones

Measure	User-Filled Applicator First, Then Prefilled User-filled paper applicator (filled using a tube of Tenofovir 1% gel)used twice daily in first intervention period and prefilled applicator used twice daily in second intervention period (after washout period)	Prefilled Applicator First, Then User-filled Plastic applicator (prefilled with Tenofovir 1% gel) used twice daily in first intervention period and user-filled applicator used twice daily in second intervention period (after washout period)
First Intervention STARTED	13	12
First Intervention COMPLETED	13	12
First Intervention NOT COMPLETED	0	0
Washout Period of at Least 21 Days STARTED	13	12
Washout Period of at Least 21 Days COMPLETED	13	12
Washout Period of at Least 21 Days NOT COMPLETED	0	0
Second Intervention STARTED	13	12
Second Intervention COMPLETED	13	12
Second Intervention NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Comparative Safety Study of Two Vaginal Applicators With Tenofovir

Baseline characteristics by cohort

Measure	Entire Study Population n=25 Participants Includes groups randomized to use the prefilled applicator first and the user-filled applicator first.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	25 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age Continuous	33 years STANDARD_DEVIATION 6 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment Dominican Republic	25 participants n=5 Participants

PRIMARY outcome

Timeframe: 7 days

Population: The number of participants for analysis was determined by counting the number of participants with colposcopic findings and baseline and after one week of product use.

Comparison of colposcopic findings between baseline visits and after one week of twice-daily application of Tenofovir 1% gel with either a user-filled or prefilled applicator

Outcome measures

Measure	User-Filled Applicator n=8 colposcopic findings paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator n=4 colposcopic findings plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Number of Colposcopic Findings (Baseline and After One Week of Product Use) Petechiae	3 colposcopic findings	0 colposcopic findings	—
Number of Colposcopic Findings (Baseline and After One Week of Product Use) Laceration external genitalia	2 colposcopic findings	0 colposcopic findings	—
Number of Colposcopic Findings (Baseline and After One Week of Product Use) Peeling cervic or vagina	1 colposcopic findings	3 colposcopic findings	—
Number of Colposcopic Findings (Baseline and After One Week of Product Use) Petechiae (iatrogenic)	1 colposcopic findings	1 colposcopic findings	—
Number of Colposcopic Findings (Baseline and After One Week of Product Use) Ecchymosis left lateral vaginal wall (iatrogenic)	1 colposcopic findings	0 colposcopic findings	—

SECONDARY outcome

Timeframe: 3 dose delivery measurements during 1 week of product use

Population: Per protocol all participants were included in the analysis.

At each dose delivery visit, the applicator was weighed, prior to vaginal insertion. For the user-filled applicator, the participant handed the applicator to the investigator after filling with gel from the multidose tube. The applicator was then weighed and returned to the participant for insertion. For the prefilled applicator, the participant inserted the plunger into the barrel, and then handed the applicator to the investigator for weighing.

Outcome measures

Measure	User-Filled Applicator n=75 filled volume paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator n=75 filled volume plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Filled Volume	4.22 ml Standard Deviation .24	4.11 ml Standard Deviation .07	—

SECONDARY outcome

Timeframe: 3 dose delivery measurements during 1 week of product use

Population: Per protocol all participants were included in the analysis.

A 5% range was calculated around the average filled volumes to determine how many applicators were filled within this range (+/-5% of average volume)

Outcome measures

Measure	User-Filled Applicator n=75 volume of filled applicator paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator n=75 volume of filled applicator plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Filling Precision (5% Range)	69 doses	75 doses	—

SECONDARY outcome

Timeframe: 3 dose delivery measurements during 1 week of product use

Population: Per protocol all participants were included in the analysis.

A 10% range was calculated around the average filled volumes to determine how many applicators were filled within this range (+/-10% of average volume)

Outcome measures

Measure	User-Filled Applicator n=75 volume of filled applicators paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator n=75 volume of filled applicators plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Filling Precision (10% Range)	74 doses	75 doses	—

SECONDARY outcome

Timeframe: 3 dose delivery measurements during 1 week of product use

Population: Per protocol all participants were included in the analysis.

The target dose for Tenofovir gel in this study was 4.0ml, which is the volume of Tenofovir being used in current microbicide clinical trials. The filled volume for each applicator was compared with the intended target dose of 4.0ml.

Outcome measures

Measure	User-Filled Applicator n=75 volume of filled applicator paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator n=75 volume of filled applicator plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Filling Accuracy (% of Target Dose)	105.5 % of target dose filled into applicator	102.8 % of target dose filled into applicator	—

SECONDARY outcome

Timeframe: 3 dose delivery measurements during 1 week of product use

Population: Per protocol, all participants were included in the analysis.

At each dose delivery visit, the applicator was weighed prior to vaginal insertion and after use. The volume of gel expressed was measured using the following data: weight of filled applicator, weight of emptied applicator, the average weight of an empty applicator, and gel density.

Outcome measures

Measure	User-Filled Applicator n=75 dosing volume paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator n=75 dosing volume plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Dosing Volume (Expressed Volume)	3.83 ml Standard Deviation .35	NA ml Standard Deviation NA As a result of an error in the interpretation of the user instructions, the dose delivery data for the prefilled applicator was not valid.	—

SECONDARY outcome

Timeframe: 3 dose delivery measurements during 1 week of product use

Population: Per protocol all participants were included in the analysis.

A 5% range was calculated around the average expressed volume of 3.83ml to determine how many applicators delivered a dose within this range (+/-5% of average volume)

Outcome measures

Measure	User-Filled Applicator n=75 dosing volume paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator n=75 dosing volume plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Dosing Precision, 5% (Expressed Volume)	48 doses	NA doses As a result of an error in the interpretation of the user instructions, the dose delivery data for the prefilled applicator was not valid.	—

SECONDARY outcome

Timeframe: 3 dose delivery measurements during 1 week of product use

Population: Per protocol all participants were included in the analysis.

A 10% range was calculated around the average expressed volume of 3.83ml to determine how many applicators delivered a dose within this range (+/-10% of average volume)

Outcome measures

Measure	User-Filled Applicator n=75 dosing volume paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator n=75 dosing volume plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Dosing Precision, 10% (Expressed Volume)	64 doses	NA doses As a result of an error in the interpretation of the user instructions, the dose delivery data for the prefilled applicator was not valid.	—

SECONDARY outcome

Timeframe: 3 dose delivery measurements during 1 week of product use

Population: Per protocol all participants were included in the analysis.

The target dose for Tenofovir gel in this study was 4.0ml, which is the volume of Tenofovir being used in current microbicide clinical trials. The average dose delivered for each applicator was compared with the intended target dose of 4.0ml.

Outcome measures

Measure	User-Filled Applicator n=75 dosing volume paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator n=75 dosing volume plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Dosing Accuracy (% of Target Dose Delivered)	96 percent of target dose delivered	NA percent of target dose delivered As a result of an error in the interpretation of the user instructions, the dose delivery data for the prefilled applicator was not valid.	—

SECONDARY outcome

Timeframe: Final study visit (after completing both study arms)

Population: All participants were included in the analysis.

Participants were asked to describe the process of filling the user-filled applicator.

Response categories included "easy", "moderately difficult", and "difficult".

Since "ease of filling" only applies to the user-filled applicator, this question was not applicable for the prefilled applicator.

Outcome measures

Measure	User-Filled Applicator n=25 Participants paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Number of Participants Reporting Applicator Easy to Fill Easy	25 participants	—	—
Number of Participants Reporting Applicator Easy to Fill Moderately difficult	0 participants	—	—
Number of Participants Reporting Applicator Easy to Fill Difficult	0 participants	—	—

SECONDARY outcome

Timeframe: Final study visit (after completing both study arms)

Population: All participants were included in the analysis.

Participants were asked when using the user-filled applicator, how confident did they feel that they at inserted the correct amount of gel into the applicator.

Response categories included "very confident", "confident", and "not confident".

(Note: this question does not apply to the prefilled applicator.)

Outcome measures

Measure	User-Filled Applicator n=25 Participants paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Number of Respondents Reporting Confidence With Filling the User-filled Applicator Very confident	4 participants	—	—
Number of Respondents Reporting Confidence With Filling the User-filled Applicator Confident	21 participants	—	—
Number of Respondents Reporting Confidence With Filling the User-filled Applicator Not confident	0 participants	—	—

SECONDARY outcome

Timeframe: Final study visit (after completing both study arms)

Population: All participants were included in the analysis. Each participant could identify multiple reasons. As a result, the number of units analyzed is greater than the number of participants.

Participants were asked how did they know when the applicator was filled correctly (that is, with the right amount of gel). More than one answer was allowed.

Response categories included "plunger automatically stopped", "the 'FULL' line was reached", and "other".

Note: this question does not apply to the prefilled applicator.

Outcome measures

Measure	User-Filled Applicator n=29 responses paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Reasons Given by Participants for Knowing When the Applicator Was Filled Correctly Plunger automatically stopped	9 participants	—	—
Reasons Given by Participants for Knowing When the Applicator Was Filled Correctly The fill line/arrow was reached	18 participants	—	—
Reasons Given by Participants for Knowing When the Applicator Was Filled Correctly Other	2 participants	—	—

SECONDARY outcome

Timeframe: Final study visit (after completing both study arms)

Population: All participants were included in the analysis.

Participants were asked to describe the insertion of the applicator into the vagina for each applicator (user-filled and prefilled).

Response categories included "easy", "moderately difficult", and "difficult".

Outcome measures

Measure	User-Filled Applicator n=25 Participants paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator n=25 Participants plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Number of Participants Reporting Applicator Easy to Insert Easy	21 participants	22 participants	—
Number of Participants Reporting Applicator Easy to Insert Moderately difficult	2 participants	3 participants	—
Number of Participants Reporting Applicator Easy to Insert Difficult	2 participants	0 participants	—

SECONDARY outcome

Timeframe: Final study visit (after completing both study arms)

Population: All participants were included in the analysis.

Participants were asked to describe the dispensing of the gel into the vagina with each applicator (user-filled and prefilled).

Response categories included "easy", "moderately difficult", and "difficult".

Outcome measures

Measure	User-Filled Applicator n=25 Participants paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator n=25 Participants plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Number of Participants Reporting That the Gel Was Easy to Dispense Easy	24 participants	23 participants	—
Number of Participants Reporting That the Gel Was Easy to Dispense Moderately difficult	1 participants	2 participants	—
Number of Participants Reporting That the Gel Was Easy to Dispense Difficult	0 participants	0 participants	—

SECONDARY outcome

Timeframe: Final study visit (after completing both study arms)

Population: All participants were included in the analysis.

Participants were asked about their preference for either the user-filled or prefilled applicator with regard to several use factors as well as in relation to disposal, storage, and overall comfort and preference.

Response categories included "user-filled", "prefilled", and "same".

Outcome measures

Measure	User-Filled Applicator n=25 Participants paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator n=25 Participants plastic applicator (prefilled with Tenofovir 1% gel)	Same n=25 Participants no preference between user-filled or prefilled applicator
Number of Participants Reporting Applicator Preference (User-filled or Prefilled) Across a Variety of Factors Ease of use	10 responses	11 responses	4 responses
Number of Participants Reporting Applicator Preference (User-filled or Prefilled) Across a Variety of Factors Ease of insertion	12 responses	10 responses	3 responses
Number of Participants Reporting Applicator Preference (User-filled or Prefilled) Across a Variety of Factors Ease of dispensing gel	8 responses	8 responses	9 responses
Number of Participants Reporting Applicator Preference (User-filled or Prefilled) Across a Variety of Factors Ease of disposal	19 responses	0 responses	6 responses
Number of Participants Reporting Applicator Preference (User-filled or Prefilled) Across a Variety of Factors Ease of storage	3 responses	16 responses	6 responses
Number of Participants Reporting Applicator Preference (User-filled or Prefilled) Across a Variety of Factors Overall comfort	11 responses	10 responses	4 responses
Number of Participants Reporting Applicator Preference (User-filled or Prefilled) Across a Variety of Factors Overall applicator preference	15 responses	10 responses	0 responses

SECONDARY outcome

Timeframe: Final study visit (after completing both study arms)

Population: All participants were included in the analysis.

Participants were asked to describe the comfort of use for each applicator type(user-filled and prefilled).

Response categories included "comfortable", "neutral", and "uncomfortable".

Outcome measures

Measure	User-Filled Applicator n=25 Participants paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator n=25 Participants plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Number of Participants Reporting That Applicator Was Comfortable to Use Comfortable	19 participants	20 participants	—
Number of Participants Reporting That Applicator Was Comfortable to Use Neutral	6 participants	5 participants	—
Number of Participants Reporting That Applicator Was Comfortable to Use Uncomfortable	0 participants	0 participants	—

SECONDARY outcome

Timeframe: Final study visit (after completing both study arms)

Population: All participants were included in the analysis.

Participants were asked if they could suggest ways that would make each applicator easier or more comfortable to use. Response categories were "yes" and "no". If yes, participants were asked to describe how they would make the applicator easier and/or more comfortable to use.

Outcome measures

Measure	User-Filled Applicator n=25 Participants paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator n=25 Participants plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Number of Participants Reporting Suggestions Regarding Ease of Use or Comfort Yes	7 participants	5 participants	—
Number of Participants Reporting Suggestions Regarding Ease of Use or Comfort No	18 participants	20 participants	—

SECONDARY outcome

Timeframe: Final study visit (after completing both study arms)

Population: All participants were included in the analysis.

For each applicator type, participants were asked if the instructions were helpful to you.

Response categories were "yes" and "no".

Outcome measures

Measure	User-Filled Applicator n=25 Participants paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator n=25 Participants plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Number of Participants Reporting That the Instructions for Use Were Helpful Yes	25 participants	25 participants	—
Number of Participants Reporting That the Instructions for Use Were Helpful No	0 participants	0 participants	—

SECONDARY outcome

Timeframe: Final study visit (after completing both study arms)

Population: All participants were included in the analysis.

Participants were asked if both applicators were acceptable to them. Responses were either "yes" or "no".

Outcome measures

Measure	User-Filled Applicator n=25 Participants paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Number of Participants Reporting That Both Applicators Were Acceptable Yes	24 participants	—	—
Number of Participants Reporting That Both Applicators Were Acceptable No	1 participants	—	—

SECONDARY outcome

Timeframe: Final study visit (after completing both study arms)

Population: All participants were included in the analysis.

Participants were asked if the cost of the applicator would influence their choice of applicator.

Response categories were "yes", "no", and "maybe".

Outcome measures

Measure	User-Filled Applicator n=25 Participants paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Number of Participants Reporting That the Cost of the Applicator Would Influence Their Choice of Applicator Yes	6 participants	—	—
Number of Participants Reporting That the Cost of the Applicator Would Influence Their Choice of Applicator No	12 participants	—	—
Number of Participants Reporting That the Cost of the Applicator Would Influence Their Choice of Applicator Maybe	7 participants	—	—

SECONDARY outcome

Timeframe: Final study visit (after completing both study arms)

Population: All participants were included in the analysis.

Participants were asked if they would use the user-filled applicator in the future if it came with a gel that helped prevent HIV infection.

Response categories included "yes", "no", and "in some circumstances".

Outcome measures

Measure	User-Filled Applicator n=25 Participants paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Number of Participants Reporting That They Would Use the User-filled Applicator in the Future if it Came With a Gel for HIV Prevention Yes	24 participants	—	—
Number of Participants Reporting That They Would Use the User-filled Applicator in the Future if it Came With a Gel for HIV Prevention No	0 participants	—	—
Number of Participants Reporting That They Would Use the User-filled Applicator in the Future if it Came With a Gel for HIV Prevention In some circumstances	1 participants	—	—

SECONDARY outcome

Timeframe: Final study visit (after completing both study arms)

Population: All participants were included in the analysis.

Participants were asked if there were any reasons that they would not want to use this user-filled applicator in the future if it came with a gel that helped prevent HIV infection.

Response categories included "yes", "no", and "in some circumstances".

Outcome measures

Measure	User-Filled Applicator n=25 Participants paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Number of Participants Reporting That They Would Not Want to Use the User-filled Applicator in the Future if it Came With a Gel for HIV Prevention No	23 participants	—	—
Number of Participants Reporting That They Would Not Want to Use the User-filled Applicator in the Future if it Came With a Gel for HIV Prevention Yes	2 participants	—	—
Number of Participants Reporting That They Would Not Want to Use the User-filled Applicator in the Future if it Came With a Gel for HIV Prevention In some circumstances	0 participants	—	—

SECONDARY outcome

Timeframe: Final study visit (after completing both study arms)

Population: All participants were included in the analysis.

Participants were asked if they would recommend the user-filled applicator to other women if it came with a gel that helped prevent HIV infection.

Response categories included "yes", "no", and "in some circumstances".

Outcome measures

Measure	User-Filled Applicator n=25 Participants paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator plastic applicator (prefilled with Tenofovir 1% gel)	Same no preference between user-filled or prefilled applicator
Number of Participants Reporting That They Would Recommend the User-filled Applicator for HIV Prevention Yes	25 participants	—	—
Number of Participants Reporting That They Would Recommend the User-filled Applicator for HIV Prevention No	0 participants	—	—
Number of Participants Reporting That They Would Recommend the User-filled Applicator for HIV Prevention In some circumstances	0 participants	—	—

Adverse Events

User-Filled Applicator

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Prefilled Applicator

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	User-Filled Applicator n=25 participants at risk paper applicator (filled using a tube of Tenofovir 1% gel)	Prefilled Applicator n=25 participants at risk plastic applicator (prefilled with Tenofovir 1% gel)
Nervous system disorders Headache	12.0% 3/25 • Number of events 3 • 6 months Adverse events were collected for the entire study period: January 26, 2011, to June 10, 2011.	20.0% 5/25 • Number of events 5 • 6 months Adverse events were collected for the entire study period: January 26, 2011, to June 10, 2011.
Respiratory, thoracic and mediastinal disorders Common cold	16.0% 4/25 • Number of events 4 • 6 months Adverse events were collected for the entire study period: January 26, 2011, to June 10, 2011.	4.0% 1/25 • Number of events 1 • 6 months Adverse events were collected for the entire study period: January 26, 2011, to June 10, 2011.
Gastrointestinal disorders Gastritis	8.0% 2/25 • Number of events 2 • 6 months Adverse events were collected for the entire study period: January 26, 2011, to June 10, 2011.	4.0% 1/25 • Number of events 2 • 6 months Adverse events were collected for the entire study period: January 26, 2011, to June 10, 2011.
Gastrointestinal disorders Tooth pain	8.0% 2/25 • Number of events 2 • 6 months Adverse events were collected for the entire study period: January 26, 2011, to June 10, 2011.	0.00% 0/25 • 6 months Adverse events were collected for the entire study period: January 26, 2011, to June 10, 2011.

Additional Information

Jessica Cohen

PATH

Phone: 206-285-3500

Email: jcohen@path.org

Results disclosure agreements

• Principal investigator is a sponsor employee Investigators have agreed to provide drug sponsor with a copy of any draft manuscript or abstract for its review and comment at least thirty days prior to submission for publication and provide a copy of any draft presentation at least seven days in advance of any scientific meeting or conference.
• Publication restrictions are in place

Restriction type: OTHER