Trial Outcomes & Findings for Pharmacologic Strategies for the Etonogestrel Implant in HIV-Infected Women (NCT NCT03282799)

NCT ID: NCT03282799

Last Updated: 2024-09-05

Results Overview

Proportion of participants that experience at least one ovulation during month 3 of etonogestrel implant use. Serum progesterone concentrations are measured weekly during month 3 (weeks 9-12). Ovulation is defined as endogenous progesterone concentrations of \>3 ng/mL.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

72 participants

Primary outcome timeframe

3 months

Results posted on

2024-09-05

Participant Flow

Participant milestones

Participant milestones
Measure
Standard Dose Etonogestrel Implant
Single 68 mg etonogestrel implant etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Increased Dose Etonogestrel Implant
Two 68 mg (136 mg total) etonogestrel implants etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Overall Study
STARTED
36
36
Overall Study
COMPLETED
34
36
Overall Study
NOT COMPLETED
2
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Standard Dose Etonogestrel Implant
Single 68 mg etonogestrel implant etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Increased Dose Etonogestrel Implant
Two 68 mg (136 mg total) etonogestrel implants etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Overall Study
Pregnancy
1
0
Overall Study
Physician Decision
1
0

Baseline Characteristics

Pharmacologic Strategies for the Etonogestrel Implant in HIV-Infected Women

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Standard Dose Etonogestrel Implant
n=36 Participants
Single 68 mg etonogestrel implant etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Increased Dose Etonogestrel Implant
n=36 Participants
Two 68 mg (136 mg total) etonogestrel implants etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Total
n=72 Participants
Total of all reporting groups
Age, Continuous
32 years
n=5 Participants
30 years
n=7 Participants
31 years
n=5 Participants
Sex: Female, Male
Female
36 Participants
n=5 Participants
36 Participants
n=7 Participants
72 Participants
n=5 Participants
Sex: Female, Male
Male
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race/Ethnicity, Customized
Ganda
22 Participants
n=5 Participants
19 Participants
n=7 Participants
41 Participants
n=5 Participants
Race/Ethnicity, Customized
Nkore
5 Participants
n=5 Participants
1 Participants
n=7 Participants
6 Participants
n=5 Participants
Race/Ethnicity, Customized
Nyarwanda
2 Participants
n=5 Participants
3 Participants
n=7 Participants
5 Participants
n=5 Participants
Race/Ethnicity, Customized
Soga
2 Participants
n=5 Participants
1 Participants
n=7 Participants
3 Participants
n=5 Participants
Race/Ethnicity, Customized
Tooro
0 Participants
n=5 Participants
3 Participants
n=7 Participants
3 Participants
n=5 Participants
Race/Ethnicity, Customized
Kiga
1 Participants
n=5 Participants
3 Participants
n=7 Participants
4 Participants
n=5 Participants
Race/Ethnicity, Customized
Other
4 Participants
n=5 Participants
6 Participants
n=7 Participants
10 Participants
n=5 Participants
Region of Enrollment
Uganda
36 participants
n=5 Participants
36 participants
n=7 Participants
72 participants
n=5 Participants
Weight
60.2 kg
n=5 Participants
59.2 kg
n=7 Participants
60.0 kg
n=5 Participants
CD4+ cell count
648 cells/mm3
n=5 Participants
700 cells/mm3
n=7 Participants
669 cells/mm3
n=5 Participants
Prior live births
3 births
n=5 Participants
3 births
n=7 Participants
3 births
n=5 Participants

PRIMARY outcome

Timeframe: 3 months

Population: One participant in the standard dose arm was withdrawn at week 1 of the study due to pregnancy.

Proportion of participants that experience at least one ovulation during month 3 of etonogestrel implant use. Serum progesterone concentrations are measured weekly during month 3 (weeks 9-12). Ovulation is defined as endogenous progesterone concentrations of \>3 ng/mL.

Outcome measures

Outcome measures
Measure
Standard Dose Etonogestrel Implant
n=35 Participants
Single 68 mg etonogestrel implant etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Increased Dose Etonogestrel Implant
n=36 Participants
Two 68 mg (136 mg total) etonogestrel implants etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Proportion of Participants That Ovulate During Month 3
11 Participants
0 Participants

PRIMARY outcome

Timeframe: 6 months

Population: One participant in the standard dose arm was withdrawn at week 1 of the study due to pregnancy.

Proportion of participants that experience at least one ovulation during month 6 of etonogestrel implant use. Serum progesterone concentrations are measured weekly during month 6 (weeks 21-24). Ovulation is defined as endogenous progesterone concentrations of \>3 ng/mL.

Outcome measures

Outcome measures
Measure
Standard Dose Etonogestrel Implant
n=35 Participants
Single 68 mg etonogestrel implant etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Increased Dose Etonogestrel Implant
n=36 Participants
Two 68 mg (136 mg total) etonogestrel implants etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Proportion of Participants That Ovulate During Month 6
17 Participants
0 Participants

PRIMARY outcome

Timeframe: 12 months

Population: One participant in the standard dose arm was withdrawn at week 1 of the study due to pregnancy, and one was withdrawn at week 45 due to a mental health condition.

Proportion of participants that experience at least one ovulation during month 12 of etonogestrel implant use. Serum progesterone concentrations are measured weekly during month 12 (weeks 45-48). Ovulation is defined as endogenous progesterone concentrations of \>3 ng/mL.

Outcome measures

Outcome measures
Measure
Standard Dose Etonogestrel Implant
n=34 Participants
Single 68 mg etonogestrel implant etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Increased Dose Etonogestrel Implant
n=36 Participants
Two 68 mg (136 mg total) etonogestrel implants etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Proportion of Participants That Ovulate During Month 12
19 Participants
2 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Evaluable cervical mucus samples collected from participants over 48 weeks of etonogestrel implant use. One participant in the standard dose arm was withdrawn at week 1 of the study due to pregnancy.

The proportion of World Health Organization cervical mucus scores that are greater than 10 from weekly samples collected during months 3, 6 and 12 of etonogestrel implant use. A cervical mucus score greater than 10 indicates the mucus is favorable for sperm penetration or lack of contraceptive effect. The cervical mucus score ranges from 0 indicating least favorable for sperm penetration to 15 for most favorable for sperm penetration.

Outcome measures

Outcome measures
Measure
Standard Dose Etonogestrel Implant
n=249 Cervical mucus samples
Single 68 mg etonogestrel implant etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Increased Dose Etonogestrel Implant
n=234 Cervical mucus samples
Two 68 mg (136 mg total) etonogestrel implants etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Proportion of Cervical Mucus Scores Greater Than 10
Cervical mucus score greater than 10
1 Cervical mucus samples
1 Cervical mucus samples
Proportion of Cervical Mucus Scores Greater Than 10
Cervical mucus score of 10 or less
248 Cervical mucus samples
233 Cervical mucus samples

SECONDARY outcome

Timeframe: Day 0

Population: Efavirenz concentration not evaluated for 1 participant who was discontinued due to pregnancy at 1 week.

Median efavirenz concentrations measured in plasma samples collected at enrollment, prior to insertion of the etonogestrel implant(s). Plasma efavirenz concentrations were quantified using a high-performance liquid chromatography assay with ultraviolet detection.

Outcome measures

Outcome measures
Measure
Standard Dose Etonogestrel Implant
n=35 Participants
Single 68 mg etonogestrel implant etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Increased Dose Etonogestrel Implant
n=36 Participants
Two 68 mg (136 mg total) etonogestrel implants etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Median Efavirenz Concentration at Enrollment
2.26 µg/mL
Interval 1.15 to 4.63
2.30 µg/mL
Interval 1.28 to 3.65

SECONDARY outcome

Timeframe: 4 weeks

Population: Efavirenz concentration not evaluated for 1 participant who was discontinued due to pregnancy at 1 and 1 participant who missed the 4-week visit.

Median efavirenz concentrations measured in plasma samples collected 4 weeks after insertion of the etonogestrel implant(s). Plasma efavirenz concentrations were quantified using a high-performance liquid chromatography assay with ultraviolet detection.

Outcome measures

Outcome measures
Measure
Standard Dose Etonogestrel Implant
n=34 Participants
Single 68 mg etonogestrel implant etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Increased Dose Etonogestrel Implant
n=36 Participants
Two 68 mg (136 mg total) etonogestrel implants etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Median Efavirenz Concentration at Week 4
2.41 µg/mL
Interval 1.47 to 4.26
2.23 µg/mL
Interval 1.38 to 5.46

SECONDARY outcome

Timeframe: 12 weeks

Population: Efavirenz concentration not evaluated for 1 participant who was discontinued due to pregnancy at 1 week and 1 participant who missed the 12-week visit.

Median efavirenz concentrations measured in plasma samples collected 12 weeks after insertion of the etonogestrel implant(s). Plasma efavirenz concentrations were quantified using a high-performance liquid chromatography assay with ultraviolet detection.

Outcome measures

Outcome measures
Measure
Standard Dose Etonogestrel Implant
n=34 Participants
Single 68 mg etonogestrel implant etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Increased Dose Etonogestrel Implant
n=36 Participants
Two 68 mg (136 mg total) etonogestrel implants etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Median Efavirenz Concentration at Week 12
2.10 µg/mL
Interval 1.22 to 3.99
1.88 µg/mL
Interval 1.35 to 2.87

SECONDARY outcome

Timeframe: 24 weeks

Population: Efavirenz concentration not evaluated for 1 participant who was discontinued due to pregnancy at 1 week.

Median efavirenz concentrations measured in plasma samples collected 24 weeks after insertion of the etonogestrel implant(s). Plasma efavirenz concentrations were quantified using a high-performance liquid chromatography assay with ultraviolet detection.

Outcome measures

Outcome measures
Measure
Standard Dose Etonogestrel Implant
n=35 Participants
Single 68 mg etonogestrel implant etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Increased Dose Etonogestrel Implant
n=36 Participants
Two 68 mg (136 mg total) etonogestrel implants etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Median Efavirenz Concentration at Week 24
2.26 µg/mL
Interval 1.31 to 4.12
1.76 µg/mL
Interval 1.18 to 3.47

SECONDARY outcome

Timeframe: 36 weeks

Population: Efavirenz concentration not evaluated for 1 participant who was discontinued due to pregnancy at 1 week.

Median efavirenz concentrations measured in plasma samples collected 36 weeks after insertion of the etonogestrel implant(s). Plasma efavirenz concentrations were quantified using a high-performance liquid chromatography assay with ultraviolet detection.

Outcome measures

Outcome measures
Measure
Standard Dose Etonogestrel Implant
n=35 Participants
Single 68 mg etonogestrel implant etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Increased Dose Etonogestrel Implant
n=36 Participants
Two 68 mg (136 mg total) etonogestrel implants etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Median Efavirenz Concentration at Week 36
1.97 µg/mL
Interval 1.18 to 5.27
1.87 µg/mL
Interval 1.09 to 4.28

SECONDARY outcome

Timeframe: 48 weeks

Population: Efavirenz concentration not evaluated for 1 participant who was discontinued due to pregnancy at 1 week and 1 participant who missed the 48-week visit.

Median efavirenz concentrations measured in plasma samples collected 48 weeks after insertion of the etonogestrel implant(s). Plasma efavirenz concentrations were quantified using a high-performance liquid chromatography assay with ultraviolet detection.

Outcome measures

Outcome measures
Measure
Standard Dose Etonogestrel Implant
n=34 Participants
Single 68 mg etonogestrel implant etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Increased Dose Etonogestrel Implant
n=36 Participants
Two 68 mg (136 mg total) etonogestrel implants etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Median Efavirenz Concentration at Week 48
2.05 µg/mL
Interval 1.36 to 3.66
1.72 µg/mL
Interval 1.01 to 2.73

SECONDARY outcome

Timeframe: 1 week

Population: Etonogestrel concentration not evaluated for 1 participant who was discontinued due to pregnancy at 1 week.

Median etonogestrel concentrations measured in plasma samples collected 1 week after insertion of the etonogestrel implant(s). Plasma etonogestrel concentrations were quantified using liquid chromatography tandem mass spectrometry.

Outcome measures

Outcome measures
Measure
Standard Dose Etonogestrel Implant
n=35 Participants
Single 68 mg etonogestrel implant etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Increased Dose Etonogestrel Implant
n=36 Participants
Two 68 mg (136 mg total) etonogestrel implants etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Median Etonogestrel Concentration at Week 1
182 pg/mL
Interval 102.0 to 303.0
439 pg/mL
Interval 327.0 to 618.0

SECONDARY outcome

Timeframe: 4 weeks

Population: Etonogestrel concentration not evaluated for 1 participant who was discontinued due to pregnancy at 1 week and 1 participant who missed the 4-week visit.

Median etonogestrel concentrations measured in plasma samples collected 4 weeks after insertion of the etonogestrel implant(s). Plasma etonogestrel concentrations were quantified using liquid chromatography tandem mass spectrometry.

Outcome measures

Outcome measures
Measure
Standard Dose Etonogestrel Implant
n=34 Participants
Single 68 mg etonogestrel implant etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Increased Dose Etonogestrel Implant
n=36 Participants
Two 68 mg (136 mg total) etonogestrel implants etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Median Etonogestrel Concentration at Week 4
115 pg/mL
Interval 79.0 to 178.0
282 pg/mL
Interval 158.0 to 414.0

SECONDARY outcome

Timeframe: 12 weeks

Population: Etonogestrel concentration not evaluated for 1 participant who was discontinued due to pregnancy at 1 week and 1 participant who missed the 12-week visit.

Median etonogestrel concentrations measured in plasma samples collected 12 weeks after insertion of the etonogestrel implant(s). Plasma etonogestrel concentrations were quantified using liquid chromatography tandem mass spectrometry.

Outcome measures

Outcome measures
Measure
Standard Dose Etonogestrel Implant
n=34 Participants
Single 68 mg etonogestrel implant etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Increased Dose Etonogestrel Implant
n=36 Participants
Two 68 mg (136 mg total) etonogestrel implants etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Median Etonogestrel Concentration at Week 12
83 pg/mL
Interval 66.0 to 99.0
214 pg/mL
Interval 124.0 to 271.0

SECONDARY outcome

Timeframe: 24 weeks

Population: Etonogestrel concentration not evaluated for 1 participant who was discontinued due to pregnancy at 1 week.

Median etonogestrel concentrations measured in plasma samples collected 24 weeks after insertion of the etonogestrel implant(s). Plasma etonogestrel concentrations were quantified using liquid chromatography tandem mass spectrometry.

Outcome measures

Outcome measures
Measure
Standard Dose Etonogestrel Implant
n=35 Participants
Single 68 mg etonogestrel implant etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Increased Dose Etonogestrel Implant
n=36 Participants
Two 68 mg (136 mg total) etonogestrel implants etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Median Etonogestrel Concentration at Week 24
69 pg/mL
Interval 41.0 to 99.0
168 pg/mL
Interval 91.0 to 224.0

SECONDARY outcome

Timeframe: 36 weeks

Population: Etonogestrel concentration not evaluated for 1 participant who was discontinued due to pregnancy at 1 week.

Median etonogestrel concentrations measured in plasma samples collected 36 weeks after insertion of the etonogestrel implant(s). Plasma etonogestrel concentrations were quantified using liquid chromatography tandem mass spectrometry.

Outcome measures

Outcome measures
Measure
Standard Dose Etonogestrel Implant
n=35 Participants
Single 68 mg etonogestrel implant etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Increased Dose Etonogestrel Implant
n=36 Participants
Two 68 mg (136 mg total) etonogestrel implants etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Median Etonogestrel Concentration at Week 36
54 pg/mL
Interval 42.0 to 71.0
132 pg/mL
Interval 75.0 to 157.0

SECONDARY outcome

Timeframe: 48 weeks

Population: Etonogestrel concentration not evaluated for 1 participant who was discontinued due to pregnancy at 1 week and 1 participant who missed the 48-week visit.

Median etonogestrel concentrations measured in plasma samples collected 48 weeks after insertion of the etonogestrel implant(s). Plasma etonogestrel concentrations were quantified using liquid chromatography tandem mass spectrometry.

Outcome measures

Outcome measures
Measure
Standard Dose Etonogestrel Implant
n=34 Participants
Single 68 mg etonogestrel implant etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Increased Dose Etonogestrel Implant
n=36 Participants
Two 68 mg (136 mg total) etonogestrel implants etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Median Etonogestrel Concentration at Week 48
39 pg/mL
Interval 25.0 to 64.0
95 pg/mL
Interval 69.0 to 137.0

Adverse Events

Standard Dose Etonogestrel Implant

Serious events: 0 serious events
Other events: 35 other events
Deaths: 0 deaths

Increased Dose Etonogestrel Implant

Serious events: 0 serious events
Other events: 35 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Standard Dose Etonogestrel Implant
n=36 participants at risk
Single 68 mg etonogestrel implant etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Increased Dose Etonogestrel Implant
n=36 participants at risk
Two 68 mg (136 mg total) etonogestrel implants etonogestrel implant: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
Reproductive system and breast disorders
Amenorrhea
5.6%
2/36 • Number of events 2 • 48 weeks
8.3%
3/36 • Number of events 3 • 48 weeks
Reproductive system and breast disorders
Menorrhagia
63.9%
23/36 • Number of events 40 • 48 weeks
83.3%
30/36 • Number of events 68 • 48 weeks
Reproductive system and breast disorders
Metrorrhagia
38.9%
14/36 • Number of events 20 • 48 weeks
61.1%
22/36 • Number of events 33 • 48 weeks
Reproductive system and breast disorders
Dysmenorrhea
22.2%
8/36 • Number of events 10 • 48 weeks
27.8%
10/36 • Number of events 12 • 48 weeks
General disorders
Weight Gain
2.8%
1/36 • Number of events 1 • 48 weeks
8.3%
3/36 • Number of events 3 • 48 weeks
Nervous system disorders
Headache
44.4%
16/36 • Number of events 26 • 48 weeks
41.7%
15/36 • Number of events 23 • 48 weeks
Reproductive system and breast disorders
Breast Tenderness
2.8%
1/36 • Number of events 2 • 48 weeks
11.1%
4/36 • Number of events 5 • 48 weeks
Gastrointestinal disorders
Nausea
11.1%
4/36 • Number of events 5 • 48 weeks
11.1%
4/36 • Number of events 4 • 48 weeks
Skin and subcutaneous tissue disorders
Acne
25.0%
9/36 • Number of events 9 • 48 weeks
16.7%
6/36 • Number of events 6 • 48 weeks
Product Issues
Implant Site Reaction
41.7%
15/36 • Number of events 19 • 48 weeks
66.7%
24/36 • Number of events 29 • 48 weeks

Additional Information

Dr. Catherine Chappell

University of Pittsburgh

Phone: 412-641-1403

Results disclosure agreements

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