Trial Outcomes & Findings for A Bioequivalence Study of IMPLANON and Radiopaque IMPLANON (34528)(P05720) (NCT NCT00620464)
NCT ID: NCT00620464
Last Updated: 2022-02-04
Results Overview
Bioequivalence testing was performed based on serum etonogestrel AUC0-6months, AUC0-24months, and AUC0-36months. Bioequivalence was to be concluded when the 90% confidence limits of AUC0-6months, AUC0-24months, and AUC0-36months were fully contained within the acceptance range of 0.80-1.25. AUC0-6months (Area under the curve from zero to six months). AUC0-24months (Area under the curve from zero to 24 months). AUC0-36months (Area under the curve from zero to 36 months).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
108 participants
Primary outcome timeframe
3 years
Results posted on
2022-02-04
Participant Flow
Participant milestones
| Measure |
Radiopaque Implanon (ro Imp)
The radiopaque rod (Radiopaque Implanon) is similar to the Implanon rod except for the addition of barium sulfate.
|
Implanon (Imp)
Implanon® (Org 32222) is a single rod contraceptive implant of 4 cm length and 2 mm in diameter. Implanon® contains approximately 68 mg etonogestrel (ENG) (Org 3236, 3-ketodesogestrel) dispersed in a matrix of ethylene vinyl acetate (EVA)copolymer, surrounded by an EVA membrane.
The ENG dose released by Implanon® amounts to about 60-70 μg/day shortly after insertion and decreases to about 40 μg/day at the start of the second year, and to about 25-30 μg/day at the end of the third year.
|
|---|---|---|
|
Overall Study
STARTED
|
52
|
56
|
|
Overall Study
COMPLETED
|
32
|
32
|
|
Overall Study
NOT COMPLETED
|
20
|
24
|
Reasons for withdrawal
| Measure |
Radiopaque Implanon (ro Imp)
The radiopaque rod (Radiopaque Implanon) is similar to the Implanon rod except for the addition of barium sulfate.
|
Implanon (Imp)
Implanon® (Org 32222) is a single rod contraceptive implant of 4 cm length and 2 mm in diameter. Implanon® contains approximately 68 mg etonogestrel (ENG) (Org 3236, 3-ketodesogestrel) dispersed in a matrix of ethylene vinyl acetate (EVA)copolymer, surrounded by an EVA membrane.
The ENG dose released by Implanon® amounts to about 60-70 μg/day shortly after insertion and decreases to about 40 μg/day at the start of the second year, and to about 25-30 μg/day at the end of the third year.
|
|---|---|---|
|
Overall Study
Adverse Event
|
15
|
17
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
|
Overall Study
Planning Pregnancy
|
1
|
4
|
|
Overall Study
Personal
|
2
|
2
|
|
Overall Study
Used prohibited medication
|
1
|
0
|
Baseline Characteristics
A Bioequivalence Study of IMPLANON and Radiopaque IMPLANON (34528)(P05720)
Baseline characteristics by cohort
| Measure |
Radiopaque Implanon (ro Imp)
n=52 Participants
The radiopaque rod (Radiopaque Implanon) is similar to the Implanon rod except for the addition of barium sulfate.
|
Implanon (Imp)
n=56 Participants
Implanon® (Org 32222) is a single rod contraceptive implant of 4 cm length and 2 mm in diameter. Implanon® contains approximately 68 mg etonogestrel (ENG) (Org 3236, 3-ketodesogestrel) dispersed in a matrix of ethylene vinyl acetate (EVA)copolymer, surrounded by an EVA membrane.
The ENG dose released by Implanon® amounts to about 60-70 μg/day shortly after insertion and decreases to about 40 μg/day at the start of the second year, and to about 25-30 μg/day at the end of the third year.
|
Total
n=108 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
18-20 years
|
11 participants
n=5 Participants
|
12 participants
n=7 Participants
|
23 participants
n=5 Participants
|
|
Age, Customized
21-25 years
|
9 participants
n=5 Participants
|
18 participants
n=7 Participants
|
27 participants
n=5 Participants
|
|
Age, Customized
26-30 years
|
15 participants
n=5 Participants
|
10 participants
n=7 Participants
|
25 participants
n=5 Participants
|
|
Age, Customized
31-35 years
|
6 participants
n=5 Participants
|
12 participants
n=7 Participants
|
18 participants
n=5 Participants
|
|
Age, Customized
36-40 years
|
10 participants
n=5 Participants
|
4 participants
n=7 Participants
|
14 participants
n=5 Participants
|
|
Age, Customized
41-45 years
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
52 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
108 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 yearsPopulation: 103 subjects were pharmacokinetically evaluable. Subjects were excluded from PK evaluation for use of protocol-prohibited steroidal medication during the trial or contraceptives within 1 week prior to Implanon insertion, or because their pre-insertion ENG concentration was not proven to be below the Lower Limit of Quantification (LLOQ)
Bioequivalence testing was performed based on serum etonogestrel AUC0-6months, AUC0-24months, and AUC0-36months. Bioequivalence was to be concluded when the 90% confidence limits of AUC0-6months, AUC0-24months, and AUC0-36months were fully contained within the acceptance range of 0.80-1.25. AUC0-6months (Area under the curve from zero to six months). AUC0-24months (Area under the curve from zero to 24 months). AUC0-36months (Area under the curve from zero to 36 months).
Outcome measures
| Measure |
Radiopaque Implanon (ro Imp)
n=50 Participants
The radiopaque rod (Radiopaque Implanon) is similar to the Implanon rod except for the addition of barium sulfate.
|
Implanon (Imp)
n=53 Participants
Implanon® (Org 32222) is a single rod contraceptive implant of 4 cm length and 2 mm in diameter. Implanon® contains approximately 68 mg etonogestrel (ENG) (Org 3236, 3-ketodesogestrel) dispersed in a matrix of ethylene vinyl acetate (EVA)copolymer, surrounded by an EVA membrane.
The ENG dose released by Implanon® amounts to about 60-70 μg/day shortly after insertion and decreases to about 40 μg/day at the start of the second year, and to about 25-30 μg/day at the end of the third year.
|
|---|---|---|
|
Bioequivalence of Implanon® and Radiopaque Implanon.
AUC (0-6 months) (n=46 ro imp; n=46 imp)
|
2296 pg•month/mL
Interval 1320.0 to 4033.0
|
2290 pg•month/mL
Interval 1386.0 to 3773.0
|
|
Bioequivalence of Implanon® and Radiopaque Implanon.
AUC (0-24 months) (n=37 ro imp; n=32 imp)
|
5954 pg•month/mL
Interval 3687.0 to 10080.0
|
6131 pg•month/mL
Interval 3625.0 to 11500.0
|
|
Bioequivalence of Implanon® and Radiopaque Implanon.
AUC (0-36 months) (n=32 ro imp; n=30 imp)
|
7667 pg•month/mL
Interval 4702.0 to 12620.0
|
7819 pg•month/mL
Interval 4843.0 to 15114.0
|
PRIMARY outcome
Timeframe: 3 yearsPopulation: All-Subjects-Pharmacokinetically-Evaluable consisted of 103 subjects.Subjects excluded from PK evaluation due to age, use of by protocol prohibited steroidal medication during trial and contraceptives within one week prior to Implanon insertion and their pre-insertion ENG concentration was not proven to be below Lower Limit Of Quantification (LLOQ)
Bioequivalence testing was performed based on serum etonogestrel Cmax. Bioequivalence was to be concluded when the 90% confidence limits of Cmax were fully contained within the acceptance range of 0.80-1.25. Cmax (pg/mL): Peak concentration.
Outcome measures
| Measure |
Radiopaque Implanon (ro Imp)
n=50 Participants
The radiopaque rod (Radiopaque Implanon) is similar to the Implanon rod except for the addition of barium sulfate.
|
Implanon (Imp)
n=53 Participants
Implanon® (Org 32222) is a single rod contraceptive implant of 4 cm length and 2 mm in diameter. Implanon® contains approximately 68 mg etonogestrel (ENG) (Org 3236, 3-ketodesogestrel) dispersed in a matrix of ethylene vinyl acetate (EVA)copolymer, surrounded by an EVA membrane.
The ENG dose released by Implanon® amounts to about 60-70 μg/day shortly after insertion and decreases to about 40 μg/day at the start of the second year, and to about 25-30 μg/day at the end of the third year.
|
|---|---|---|
|
Bioequivalence of Implanon® and Radiopaque Implanon
|
1200 pg/mL
Interval 509.0 to 3030.0
|
1145 pg/mL
Interval 317.0 to 3100.0
|
Adverse Events
Implanon
Serious events: 6 serious events
Other events: 54 other events
Deaths: 0 deaths
Radiopaque Implanon
Serious events: 4 serious events
Other events: 48 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Implanon
n=56 participants at risk
Implanon® (Org 32222) is a single rod contraceptive implant of 4 cm length and 2 mm in diameter. Implanon® contains approximately 68 mg etonogestrel (ENG) (Org 3236, 3-ketodesogestrel) dispersed in a matrix of ethylene vinyl acetate (EVA)copolymer, surrounded by an EVA membrane.
The ENG dose released by Implanon® amounts to about 60-70 μg/day shortly after insertion and decreases to about 40 μg/day at the start of the second year, and to about 25-30 μg/day at the end of the third year.
|
Radiopaque Implanon
n=52 participants at risk
The radiopaque rod (Radiopaque Implanon) is similar to the Implanon rod except for the addition of barium sulfate.
|
|---|---|---|
|
Injury, poisoning and procedural complications
Ligament rupture
|
1.8%
1/56 • Number of events 1
|
0.00%
0/52
|
|
Injury, poisoning and procedural complications
Peripheral nerve injury
|
0.00%
0/56
|
1.9%
1/52 • Number of events 1
|
|
Injury, poisoning and procedural complications
Tendon injury
|
0.00%
0/56
|
1.9%
1/52 • Number of events 1
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.00%
0/56
|
1.9%
1/52 • Number of events 1
|
|
Injury, poisoning and procedural complications
Vertebral injury
|
1.8%
1/56 • Number of events 1
|
0.00%
0/52
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
1.8%
1/56 • Number of events 1
|
0.00%
0/52
|
|
Psychiatric disorders
Eating disorder
|
1.8%
1/56 • Number of events 1
|
0.00%
0/52
|
|
Surgical and medical procedures
Mammoplasty
|
1.8%
1/56 • Number of events 1
|
0.00%
0/52
|
|
Surgical and medical procedures
Scar excision
|
1.8%
1/56 • Number of events 1
|
0.00%
0/52
|
|
Vascular disorders
Deep vein thrombosis
|
1.8%
1/56 • Number of events 1
|
1.9%
1/52 • Number of events 1
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
0.00%
0/56
|
1.9%
1/52 • Number of events 1
|
Other adverse events
| Measure |
Implanon
n=56 participants at risk
Implanon® (Org 32222) is a single rod contraceptive implant of 4 cm length and 2 mm in diameter. Implanon® contains approximately 68 mg etonogestrel (ENG) (Org 3236, 3-ketodesogestrel) dispersed in a matrix of ethylene vinyl acetate (EVA)copolymer, surrounded by an EVA membrane.
The ENG dose released by Implanon® amounts to about 60-70 μg/day shortly after insertion and decreases to about 40 μg/day at the start of the second year, and to about 25-30 μg/day at the end of the third year.
|
Radiopaque Implanon
n=52 participants at risk
The radiopaque rod (Radiopaque Implanon) is similar to the Implanon rod except for the addition of barium sulfate.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
3.6%
2/56 • Number of events 2
|
11.5%
6/52 • Number of events 7
|
|
Gastrointestinal disorders
Diarrhoea
|
5.4%
3/56 • Number of events 3
|
9.6%
5/52 • Number of events 7
|
|
Gastrointestinal disorders
Nausea
|
14.3%
8/56 • Number of events 9
|
11.5%
6/52 • Number of events 8
|
|
Gastrointestinal disorders
Toothache
|
5.4%
3/56 • Number of events 3
|
1.9%
1/52 • Number of events 1
|
|
General disorders
Fatigue
|
5.4%
3/56 • Number of events 5
|
3.8%
2/52 • Number of events 2
|
|
General disorders
Hangover
|
3.6%
2/56 • Number of events 3
|
5.8%
3/52 • Number of events 3
|
|
General disorders
Implant site haematoma
|
28.6%
16/56 • Number of events 16
|
30.8%
16/52 • Number of events 16
|
|
General disorders
Implant site pain
|
10.7%
6/56 • Number of events 9
|
7.7%
4/52 • Number of events 5
|
|
Immune system disorders
Seasonal allergy
|
5.4%
3/56 • Number of events 5
|
3.8%
2/52 • Number of events 2
|
|
Infections and infestations
Cystitis
|
7.1%
4/56 • Number of events 4
|
15.4%
8/52 • Number of events 9
|
|
Infections and infestations
Gastroenteritis
|
7.1%
4/56 • Number of events 4
|
11.5%
6/52 • Number of events 10
|
|
Infections and infestations
Influenza
|
25.0%
14/56 • Number of events 23
|
23.1%
12/52 • Number of events 27
|
|
Infections and infestations
Nasopharyngitis
|
25.0%
14/56 • Number of events 21
|
34.6%
18/52 • Number of events 42
|
|
Infections and infestations
Sinusitis
|
5.4%
3/56 • Number of events 4
|
3.8%
2/52 • Number of events 2
|
|
Infections and infestations
Vulvovaginal candidiasis
|
3.6%
2/56 • Number of events 3
|
7.7%
4/52 • Number of events 6
|
|
Infections and infestations
Vulvovaginal mycotic infection
|
12.5%
7/56 • Number of events 8
|
5.8%
3/52 • Number of events 3
|
|
Injury, poisoning and procedural complications
Procedural pain
|
5.4%
3/56 • Number of events 3
|
9.6%
5/52 • Number of events 6
|
|
Investigations
Weight decreased
|
7.1%
4/56 • Number of events 4
|
1.9%
1/52 • Number of events 1
|
|
Investigations
Weight increased
|
14.3%
8/56 • Number of events 8
|
7.7%
4/52 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.1%
4/56 • Number of events 5
|
7.7%
4/52 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.7%
6/56 • Number of events 9
|
21.2%
11/52 • Number of events 19
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
1.8%
1/56 • Number of events 1
|
5.8%
3/52 • Number of events 8
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/56
|
5.8%
3/52 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
1.8%
1/56 • Number of events 1
|
7.7%
4/52 • Number of events 4
|
|
Nervous system disorders
Dizziness
|
8.9%
5/56 • Number of events 6
|
9.6%
5/52 • Number of events 5
|
|
Nervous system disorders
Headache
|
26.8%
15/56 • Number of events 38
|
26.9%
14/52 • Number of events 39
|
|
Reproductive system and breast disorders
Amenorrhoea
|
10.7%
6/56 • Number of events 7
|
5.8%
3/52 • Number of events 3
|
|
Reproductive system and breast disorders
Breast pain
|
7.1%
4/56 • Number of events 5
|
7.7%
4/52 • Number of events 5
|
|
Reproductive system and breast disorders
Breast tenderness
|
1.8%
1/56 • Number of events 1
|
7.7%
4/52 • Number of events 6
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
7.1%
4/56 • Number of events 9
|
11.5%
6/52 • Number of events 19
|
|
Reproductive system and breast disorders
Genital haemorrhage
|
41.1%
23/56 • Number of events 52
|
46.2%
24/52 • Number of events 69
|
|
Reproductive system and breast disorders
Metrorrhagia
|
16.1%
9/56 • Number of events 11
|
17.3%
9/52 • Number of events 10
|
|
Reproductive system and breast disorders
Oligomenorrhoea
|
5.4%
3/56 • Number of events 3
|
0.00%
0/52
|
|
Reproductive system and breast disorders
Pelvic pain
|
8.9%
5/56 • Number of events 8
|
5.8%
3/52 • Number of events 4
|
|
Reproductive system and breast disorders
Polymenorrhoea
|
0.00%
0/56
|
5.8%
3/52 • Number of events 4
|
|
Reproductive system and breast disorders
Vaginal discharge
|
5.4%
3/56 • Number of events 5
|
5.8%
3/52 • Number of events 4
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
32.1%
18/56 • Number of events 63
|
40.4%
21/52 • Number of events 151
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.4%
3/56 • Number of events 4
|
5.8%
3/52 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.1%
4/56 • Number of events 4
|
9.6%
5/52 • Number of events 8
|
|
Skin and subcutaneous tissue disorders
Acne
|
32.1%
18/56 • Number of events 32
|
21.2%
11/52 • Number of events 22
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.4%
3/56 • Number of events 5
|
0.00%
0/52
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee All investigator publications must be based on data validated and released by sponsor. Any such scientific paper, presentation, or other communication concerning the clinical trial will first be submitted to sponsor, at least six weeks ahead of estimated publication or presentation, for consent. In the event that no response is received within six weeks after submission, the investigator may use the submitted data.
- Publication restrictions are in place
Restriction type: OTHER