Contraception
Conditions
Brief summary
The primary purpose of this study is to demonstrate the bioequivalence of IMPLANON and Radiopaque IMPLANON.
Interventions
DRUGRadiopaque Implanon
Radiopaque rod for 3 years
DRUGImplanon (etonogestrel implant)
Implanon (etonogestrel implant) for 3 years
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* At least 18 but not older than 40 years of age at the time of screening * Good physical and mental health * Regular cycles with a usual length between 24 and 35 days * Body mass index ≥ 18 and ≤ 29 * Willing to give informed consent in writing
Exclusion criteria
* Contraindications: * known or suspected pregnancy * active venous thromboembolic disorder (e.g. deep vein thrombosis,pulmonary embolism) * presence or history of severe hepatic disease as long as liver function values have not returned to normal * malignancy or pre-malignancy, if sex -steroid-influenced * undiagnosed vaginal bleeding * hypersensitivity to any of the components of Implanon/Radiopaque Implanon * Hypertension, i.e. systolic blood pressure \>140 mmHg and/or diastolic blood pressure \> 90 mmHg. * A history during pregnancy or during previous use of sex steroids of: jaundice and/or severe pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; haemolytic uraemic syndrome; Sydenham's chorea; herpes gestationis; otosclerosis-related hearing loss * Present use or use during 2 months prior to the start of Implanon/Radiopaque Implanon of one of the following drugs: phenytoin, phenobarbital, primidone, carbamazepine, rifampicin, oxcarbazepine, topiramate, felbamate, ritonavir, nelfinavir, griseofulvin or the herbal remedy St John's wort. * Administration of investigational drugs within 2 months prior to the start of Implanon/Radiopaque Implanon
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bioequivalence of Implanon® and Radiopaque Implanon. | 3 years | 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). |
| Bioequivalence of Implanon® and Radiopaque Implanon | 3 years | 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Radiopaque Implanon (ro Imp) The radiopaque rod (Radiopaque Implanon) is similar to the Implanon rod except for the addition of barium sulfate. | 52 |
| 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. | 56 |
| Total | 108 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 15 | 17 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Personal | 2 | 2 |
| Overall Study | Planning Pregnancy | 1 | 4 |
| Overall Study | Used prohibited medication | 1 | 0 |
Baseline characteristics
| Characteristic | Radiopaque Implanon (ro Imp) | Implanon (Imp) | Total |
|---|---|---|---|
| Age, Customized 18-20 years | 11 participants | 12 participants | 23 participants |
| Age, Customized 21-25 years | 9 participants | 18 participants | 27 participants |
| Age, Customized 26-30 years | 15 participants | 10 participants | 25 participants |
| Age, Customized 31-35 years | 6 participants | 12 participants | 18 participants |
| Age, Customized 36-40 years | 10 participants | 4 participants | 14 participants |
| Age, Customized 41-45 years | 1 participants | 0 participants | 1 participants |
| Sex: Female, Male Female | 52 Participants | 56 Participants | 108 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 54 / 56 | 48 / 52 |
| serious Total, serious adverse events | 6 / 56 | 4 / 52 |
Outcome results
Primary
Bioequivalence of Implanon® and Radiopaque Implanon
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.
Time frame: 3 years
Population: 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)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Radiopaque Implanon (ro Imp) | Bioequivalence of Implanon® and Radiopaque Implanon | 1200 pg/mL |
| Implanon (Imp) | Bioequivalence of Implanon® and Radiopaque Implanon | 1145 pg/mL |
p-value: <=0.05Bioequivalence Testing
Primary
Bioequivalence of Implanon® and Radiopaque Implanon.
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).
Time frame: 3 years
Population: 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)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Radiopaque Implanon (ro Imp) | Bioequivalence of Implanon® and Radiopaque Implanon. | AUC (0-6 months) (n=46 ro imp; n=46 imp) | 2296 pg•month/mL |
| Radiopaque Implanon (ro Imp) | Bioequivalence of Implanon® and Radiopaque Implanon. | AUC (0-24 months) (n=37 ro imp; n=32 imp) | 5954 pg•month/mL |
| Radiopaque Implanon (ro Imp) | Bioequivalence of Implanon® and Radiopaque Implanon. | AUC (0-36 months) (n=32 ro imp; n=30 imp) | 7667 pg•month/mL |
| Implanon (Imp) | Bioequivalence of Implanon® and Radiopaque Implanon. | AUC (0-6 months) (n=46 ro imp; n=46 imp) | 2290 pg•month/mL |
| Implanon (Imp) | Bioequivalence of Implanon® and Radiopaque Implanon. | AUC (0-24 months) (n=37 ro imp; n=32 imp) | 6131 pg•month/mL |
| Implanon (Imp) | Bioequivalence of Implanon® and Radiopaque Implanon. | AUC (0-36 months) (n=32 ro imp; n=30 imp) | 7819 pg•month/mL |
p-value: 0.05Bioequivalence Testing