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Trial Outcomes & Findings for Safety and Pharmacokinetics (PK) of a Polyurethane Tenofovir Disoproxil Fumarate (TDF) Vaginal Ring (NCT NCT02006264)

NCT ID: NCT02006264

Last Updated: 2018-08-28

Results Overview

Grade 1 or higher Genitourinary events as defined by the DAIDS (Division of AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events during the trial period judged to be related to study product

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

30 participants

Primary outcome timeframe

14 days of vaginal ring use

Results posted on

2018-08-28

Participant Flow

Participant milestones

Participant milestones
Measure
TDF Intravaginal Ring
TDF Intravaginal Ring (TDF-IVR) The TDF (tenofovir disoproxil fumarate) IVR (intravaginal ring) has an inner core compartment comprised of 86% w/w (weight by weight) TDF and 14% w/w sodium chloride (NaCl). The TDF intravaginal ring will be worn continuously for 14 days. It will be inserted into the vagina following cessation of participant's menses at Visit 3 and removed at Visit 7.
Placebo Intravaginal Ring
Placebo Intravaginal Ring (Placebo IVR) The placebo intravaginal ring (IVR) has an inner core which contains sodium chloride (NaCl). The intravaginal ring will be worn continuously for 14 days. It will be inserted into the vagina following cessation of participant's menses at Visit 3 and removed at Visit 7.
Overall Study
STARTED
15
15
Overall Study
COMPLETED
14
15
Overall Study
NOT COMPLETED
1
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Pharmacokinetics (PK) of a Polyurethane Tenofovir Disoproxil Fumarate (TDF) Vaginal Ring

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
TDF Intravaginal Ring
n=15 Participants
TDF Intravaginal Ring (TDF IVR)
Placebo Intravaginal Ring
n=15 Participants
Placebo Intravaginal Ring (Placebo IVR)
Total
n=30 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
15 Participants
n=5 Participants
15 Participants
n=7 Participants
30 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Continuous
30 years
STANDARD_DEVIATION 7.1 • n=5 Participants
28.2 years
STANDARD_DEVIATION 5.7 • n=7 Participants
29.65 years
STANDARD_DEVIATION 6.4 • n=5 Participants
Sex: Female, Male
Female
15 Participants
n=5 Participants
15 Participants
n=7 Participants
30 Participants
n=5 Participants
Sex: Female, Male
Male
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Region of Enrollment
United States
15 Participants
n=5 Participants
15 Participants
n=7 Participants
30 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 14 days of vaginal ring use

Grade 1 or higher Genitourinary events as defined by the DAIDS (Division of AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events during the trial period judged to be related to study product

Outcome measures

Outcome measures
Measure
TDF Intravaginal Ring
n=15 Participants
TDF Intravaginal Ring (TDF IVR)
Placebo Intravaginal Ring
n=15 Participants
Placebo Intravaginal Ring (Placebo IVR)
Grade 1 Genitourinary Events or Higher as Defined by the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events
7 Adverse events
1 Adverse events

PRIMARY outcome

Timeframe: 14 days of vaginal ring use

Grade 2 or higher systemic and local Adverse Events as defined by the Division of Aids (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events during the trial period

Outcome measures

Outcome measures
Measure
TDF Intravaginal Ring
n=15 Participants
TDF Intravaginal Ring (TDF IVR)
Placebo Intravaginal Ring
n=15 Participants
Placebo Intravaginal Ring (Placebo IVR)
Grade 2 or Higher Adverse Events as Defined by the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events
2 Adverse events
0 Adverse events

SECONDARY outcome

Timeframe: 1, 3, 7 and 14 days after ring insertion and 2 and 7 days after ring removal

Population: TDF analytical data available for 14 of 15 participants for CVF VAG and CVF ECX. PK parameters only measured in TDF IVR subjects, not Placebo IVR subjects.

TDF (tenofovir disoproxil fumarate) and TFV (tenofovir) maximum concentrations (C-max) in CVF (Cervicovaginal Fluid) genital secretions (ectocervix (ECX) and vagina (VAG)) and TFV maximum concentration (C-max) in plasma. PK parameters only measured in TDF IVR subjects, not Placebo IVR subjects.

Outcome measures

Outcome measures
Measure
TDF Intravaginal Ring
n=15 Participants
TDF Intravaginal Ring (TDF IVR)
Placebo Intravaginal Ring
Placebo Intravaginal Ring (Placebo IVR)
TDF and TFV Maximum Concentrations (C-max) in CVF Genital Secretions (ECX and VAG) and TFV Maximum Concentration in Plasma
C-max CVF VAG TDF
240000 ng/mL
Interval 140000.0 to 360000.0
—
TDF and TFV Maximum Concentrations (C-max) in CVF Genital Secretions (ECX and VAG) and TFV Maximum Concentration in Plasma
C-max CVF ECX TDF
210000 ng/mL
Interval 81000.0 to 320000.0
—
TDF and TFV Maximum Concentrations (C-max) in CVF Genital Secretions (ECX and VAG) and TFV Maximum Concentration in Plasma
C-max CVF VAG TFV
91000 ng/mL
Interval 73000.0 to 190000.0
—
TDF and TFV Maximum Concentrations (C-max) in CVF Genital Secretions (ECX and VAG) and TFV Maximum Concentration in Plasma
C-max CVF ECX TFV
85000 ng/mL
Interval 52000.0 to 170000.0
—
TDF and TFV Maximum Concentrations (C-max) in CVF Genital Secretions (ECX and VAG) and TFV Maximum Concentration in Plasma
C-max Plasma TFV
1.9 ng/mL
Interval 1.2 to 2.4
—

SECONDARY outcome

Timeframe: 1, 3, 7 and 14 days after ring insertion and 2 and 7 days after ring removal

Population: TDF analytical data available for 14 of 15 participants for CVF VAG and CVF ECX. TFV analytical data available for 12 of 15 participants for Plasma. PK parameters only measured in TDF IVR subjects, not Placebo IVR subjects.

TDF (tenofovir disoproxil fumarate) and TFV (tenofovir) time to maximum concentrations (T-max) in CVF (Cervicovaginal Fluid) genital secretions (ectocervix (ECX) and vagina (VAG)), and TFV time to maximum concentration in Plasma. PK parameters only measured in TDF IVR subjects, not Placebo IVR subjects.

Outcome measures

Outcome measures
Measure
TDF Intravaginal Ring
n=15 Participants
TDF Intravaginal Ring (TDF IVR)
Placebo Intravaginal Ring
Placebo Intravaginal Ring (Placebo IVR)
TDF and TFV Time to Maximum Concentrations (T-max) in CVF Genital Secretions (ECX and VAG), and TFV Time to Maximum Concentration in Plasma
T-max CVF VAG TDF
6 h
Interval 3.0 to 7.0
—
TDF and TFV Time to Maximum Concentrations (T-max) in CVF Genital Secretions (ECX and VAG), and TFV Time to Maximum Concentration in Plasma
T-max CVF ECX TDF
5 h
Interval 4.0 to 7.0
—
TDF and TFV Time to Maximum Concentrations (T-max) in CVF Genital Secretions (ECX and VAG), and TFV Time to Maximum Concentration in Plasma
T-max CVF VAG TFV
14 h
Interval 1.0 to 14.0
—
TDF and TFV Time to Maximum Concentrations (T-max) in CVF Genital Secretions (ECX and VAG), and TFV Time to Maximum Concentration in Plasma
T-max CVF ECX TFV
7 h
Interval 3.0 to 14.0
—
TDF and TFV Time to Maximum Concentrations (T-max) in CVF Genital Secretions (ECX and VAG), and TFV Time to Maximum Concentration in Plasma
T-max Plasma TFV
14 h
Interval 14.0 to 14.0
—

SECONDARY outcome

Timeframe: 1, 3, 7 and 14 days after ring insertion and 2 and 7 days after ring removal

Population: TDF analytical data available for 13 of 15 participants for CVF ECX, and 14 of 15 participants for CVF VAG. TFV analytical data available for 13 of 15 participants for CVF ECX. PK parameters only measured in TDF IVR subjects, not Placebo IVR subjects.

TDF (tenofovir disoproxil fumarate) AUC0-14 (Area Under the Curve (concentration versus time) days 0-14) in Cervicovaginal Fluid (CVF) genital secretions (ectocervix (ECX) and vagina(VAG)), TFV AUC0-14 in CVF genital secretions (ECX and VAG), and TFV (tenofovir) AUC0-14 in Plasma. PK parameters only measured in TDF IVR subjects, not Placebo IVR subjects.

Outcome measures

Outcome measures
Measure
TDF Intravaginal Ring
n=15 Participants
TDF Intravaginal Ring (TDF IVR)
Placebo Intravaginal Ring
Placebo Intravaginal Ring (Placebo IVR)
TDF AUC0-14 in CVF Genital Secretions (ECX and VAG), TFV AUC0-14 in CVF Genital Secretions (ECX and VAG), and TFV AUC0-14 in Plasma
AUC0-14 (days 0-14), CVF VAG TDF
2000000 ngxd/mL
Interval 690000.0 to 3200000.0
—
TDF AUC0-14 in CVF Genital Secretions (ECX and VAG), TFV AUC0-14 in CVF Genital Secretions (ECX and VAG), and TFV AUC0-14 in Plasma
AUC0-14 (days 0-14), CVF ECX TDF
1300000 ngxd/mL
Interval 340000.0 to 2100000.0
—
TDF AUC0-14 in CVF Genital Secretions (ECX and VAG), TFV AUC0-14 in CVF Genital Secretions (ECX and VAG), and TFV AUC0-14 in Plasma
AUC0-14 (days 0-14), CVF VAG TFV
1100000 ngxd/mL
Interval 670000.0 to 2100000.0
—
TDF AUC0-14 in CVF Genital Secretions (ECX and VAG), TFV AUC0-14 in CVF Genital Secretions (ECX and VAG), and TFV AUC0-14 in Plasma
AUC0-14 (days 0-14), CVF ECX TFV
970000 ngxd/mL
Interval 570000.0 to 1300000.0
—
TDF AUC0-14 in CVF Genital Secretions (ECX and VAG), TFV AUC0-14 in CVF Genital Secretions (ECX and VAG), and TFV AUC0-14 in Plasma
AUC0-14 (days 0-14), Plasma TFV
9.4 ngxd/mL
Interval 6.9 to 14.4
—

SECONDARY outcome

Timeframe: before and after 14 days of vaginal ring use

Population: PK parameters only measured in TDF IVR subjects, not Placebo IVR subjects.

TFV (tenofovir) average concentration (C-ave) in cervical tissue. PK parameters only measured in TDF IVR subjects, not Placebo IVR subjects.

Outcome measures

Outcome measures
Measure
TDF Intravaginal Ring
n=15 Participants
TDF Intravaginal Ring (TDF IVR)
Placebo Intravaginal Ring
Placebo Intravaginal Ring (Placebo IVR)
TFV C-ave in Cervical Tissue
5.4 ng/mg
Interval 2.8 to 8.8
—

SECONDARY outcome

Timeframe: before and after 14 days of vaginal ring use

Population: PK parameters only measured in TDF IVR subjects, not Placebo IVR subjects.

TFV-DP (tenofovir diphosphate) average concentration (C-ave) in cervical tissue. PK parameters only measured in TDF IVR subjects, not Placebo IVR subjects.

Outcome measures

Outcome measures
Measure
TDF Intravaginal Ring
n=15 Participants
TDF Intravaginal Ring (TDF IVR)
Placebo Intravaginal Ring
Placebo Intravaginal Ring (Placebo IVR)
TFV-DP C-ave in Cervical Tissue
120 fmol/mg
Interval 90.0 to 550.0
—

Adverse Events

TDF Intravaginal Ring

Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths

Placebo Intravaginal Ring

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
TDF Intravaginal Ring
n=15 participants at risk
TDF Intravaginal Ring (TDF IVR)
Placebo Intravaginal Ring
n=15 participants at risk
Placebo Intravaginal Ring (Placebo IVR)
Reproductive system and breast disorders
Vaginal discharge
40.0%
6/15
6.7%
1/15
Reproductive system and breast disorders
Intermenstrual bleeding
20.0%
3/15
20.0%
3/15
Reproductive system and breast disorders
Pelvic pain
13.3%
2/15
0.00%
0/15

Additional Information

Marla Keller, MD, Principal Investigator

Albert Einstein College of Medicine

Phone: 718-430-3240

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place