A Bioequivalence Study of IMPLANON and Radiopaque IMPLANON (34528)(P05720)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00620464
• Collaborator: (none)
• Enrollment: 108
• Arms: 2
• Duration (Months): 45.1

Study Details

Study Description

Brief Summary

The primary purpose of this study is to demonstrate the bioequivalence of IMPLANON and Radiopaque IMPLANON.

Condition or Disease	Intervention/Treatment	Phase
Contraception	Drug: Radiopaque Implanon; Drug: Implanon (etonogestrel implant)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 108 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Randomized, Double-Blind, Parallel Group, Bioequivalence Study of IMPLANON and Radiopaque IMPLANON
• Study Start Date: May 1, 2005
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Radiopaque Implanon (ro imp) The radiopaque rod (Radiopaque Implanon) is similar to the Implanon rod except for the addition of barium sulfate.	Drug: Radiopaque Implanon; Radiopaque rod for 3 years
Active Comparator: 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.	Drug: Implanon (etonogestrel implant); Implanon (etonogestrel implant) for 3 years

Outcome Measures

Primary Outcome Measures

1. 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).

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: Female
• Accepts 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00620464
• Other Study ID Numbers: P05720; 34528
• First Posted: Feb 21, 2008
• Last Update Posted: Feb 4, 2022
• Last Verified: Feb 1, 2022

• Additional relevant MeSH terms: Etonogestrel; Desogestrel

Study Results

Participant Flow

Arm/Group Title	Radiopaque Implanon (ro Imp)	Implanon (Imp)
Arm/Group Description	The radiopaque rod (Radiopaque Implanon) is similar to the Implanon rod except for the addition of barium sulfate.	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.
Period Title: Overall Study
STARTED	52	56
COMPLETED	32	32
NOT COMPLETED	20	24

Baseline Characteristics

Arm/Group Title	Radiopaque Implanon (ro Imp)	Implanon (Imp)	Total
Arm/Group Description	The radiopaque rod (Radiopaque Implanon) is similar to the Implanon rod except for the addition of barium sulfate.	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 of all reporting groups
Overall Participants	52	56	108
Age, Customized (participants) [Number]
18-20 years	11 21.2%	12 21.4%	23 21.3%
21-25 years	9 17.3%	18 32.1%	27 25%
26-30 years	15 28.8%	10 17.9%	25 23.1%
31-35 years	6 11.5%	12 21.4%	18 16.7%
36-40 years	10 19.2%	4 7.1%	14 13%
41-45 years	1 1.9%	0 0%	1 0.9%
Sex: Female, Male (Count of Participants)
Female	52 100%	56 100%	108 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Bioequivalence of Implanon® and Radiopaque Implanon.
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Radiopaque Implanon (ro Imp)	Implanon (Imp)
Arm/Group Description	The radiopaque rod (Radiopaque Implanon) is similar to the Implanon rod except for the addition of barium sulfate.	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.
Measure Participants	50	53
AUC (0-6 months) (n=46 ro imp; n=46 imp)	2296	2290
AUC (0-24 months) (n=37 ro imp; n=32 imp)	5954	6131
AUC (0-36 months) (n=32 ro imp; n=30 imp)	7667	7819

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Radiopaque Implanon (ro Imp), Implanon (Imp)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	Applies to all parameters.
	Method	Bioequivalence Testing
	Comments

2. Primary Outcome

Title	Bioequivalence of Implanon® and Radiopaque Implanon
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Radiopaque Implanon (ro Imp)	Implanon (Imp)
Arm/Group Description	The radiopaque rod (Radiopaque Implanon) is similar to the Implanon rod except for the addition of barium sulfate.	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.
Measure Participants	50	53
Mean (Full Range) [pg/mL]	1200	1145

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Radiopaque Implanon (ro Imp), Implanon (Imp)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<=0.05
	Comments
	Method	Bioequivalence Testing
	Comments

Adverse Events

Arm/Group Title	Implanon		Radiopaque Implanon
Arm/Group Description	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.		The radiopaque rod (Radiopaque Implanon) is similar to the Implanon rod except for the addition of barium sulfate.
All Cause Mortality
	Implanon		Radiopaque Implanon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Implanon		Radiopaque Implanon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/56 (10.7%)		4/52 (7.7%)
Injury, poisoning and procedural complications
Ligament rupture	1/56 (1.8%)	1	0/52 (0%)	0
Peripheral nerve injury	0/56 (0%)	0	1/52 (1.9%)	1
Tendon injury	0/56 (0%)	0	1/52 (1.9%)	1
Tibia fracture	0/56 (0%)	0	1/52 (1.9%)	1
Vertebral injury	1/56 (1.8%)	1	0/52 (0%)	0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/56 (1.8%)	1	0/52 (0%)	0
Psychiatric disorders
Eating disorder	1/56 (1.8%)	1	0/52 (0%)	0
Surgical and medical procedures
Mammoplasty	1/56 (1.8%)	1	0/52 (0%)	0
Scar excision	1/56 (1.8%)	1	0/52 (0%)	0
Vascular disorders
Deep vein thrombosis	1/56 (1.8%)	1	1/52 (1.9%)	1
Peripheral arterial occlusive disease	0/56 (0%)	0	1/52 (1.9%)	1
Other (Not Including Serious) Adverse Events
	Implanon		Radiopaque Implanon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/56 (96.4%)		48/52 (92.3%)
Gastrointestinal disorders
Abdominal pain	2/56 (3.6%)	2	6/52 (11.5%)	7
Diarrhoea	3/56 (5.4%)	3	5/52 (9.6%)	7
Nausea	8/56 (14.3%)	9	6/52 (11.5%)	8
Toothache	3/56 (5.4%)	3	1/52 (1.9%)	1
General disorders
Fatigue	3/56 (5.4%)	5	2/52 (3.8%)	2
Hangover	2/56 (3.6%)	3	3/52 (5.8%)	3
Implant site haematoma	16/56 (28.6%)	16	16/52 (30.8%)	16
Implant site pain	6/56 (10.7%)	9	4/52 (7.7%)	5
Immune system disorders
Seasonal allergy	3/56 (5.4%)	5	2/52 (3.8%)	2
Infections and infestations
Cystitis	4/56 (7.1%)	4	8/52 (15.4%)	9
Gastroenteritis	4/56 (7.1%)	4	6/52 (11.5%)	10
Influenza	14/56 (25%)	23	12/52 (23.1%)	27
Nasopharyngitis	14/56 (25%)	21	18/52 (34.6%)	42
Sinusitis	3/56 (5.4%)	4	2/52 (3.8%)	2
Vulvovaginal candidiasis	2/56 (3.6%)	3	4/52 (7.7%)	6
Vulvovaginal mycotic infection	7/56 (12.5%)	8	3/52 (5.8%)	3
Injury, poisoning and procedural complications
Procedural pain	3/56 (5.4%)	3	5/52 (9.6%)	6
Investigations
Weight decreased	4/56 (7.1%)	4	1/52 (1.9%)	1
Weight increased	8/56 (14.3%)	8	4/52 (7.7%)	4
Musculoskeletal and connective tissue disorders
Arthralgia	4/56 (7.1%)	5	4/52 (7.7%)	6
Back pain	6/56 (10.7%)	9	11/52 (21.2%)	19
Myalgia	1/56 (1.8%)	1	3/52 (5.8%)	8
Neck pain	0/56 (0%)	0	3/52 (5.8%)	3
Pain in extremity	1/56 (1.8%)	1	4/52 (7.7%)	4
Nervous system disorders
Dizziness	5/56 (8.9%)	6	5/52 (9.6%)	5
Headache	15/56 (26.8%)	38	14/52 (26.9%)	39
Reproductive system and breast disorders
Amenorrhoea	6/56 (10.7%)	7	3/52 (5.8%)	3
Breast pain	4/56 (7.1%)	5	4/52 (7.7%)	5
Breast tenderness	1/56 (1.8%)	1	4/52 (7.7%)	6
Dysmenorrhoea	4/56 (7.1%)	9	6/52 (11.5%)	19
Genital haemorrhage	23/56 (41.1%)	52	24/52 (46.2%)	69
Metrorrhagia	9/56 (16.1%)	11	9/52 (17.3%)	10
Oligomenorrhoea	3/56 (5.4%)	3	0/52 (0%)	0
Pelvic pain	5/56 (8.9%)	8	3/52 (5.8%)	4
Polymenorrhoea	0/56 (0%)	0	3/52 (5.8%)	4
Vaginal discharge	3/56 (5.4%)	5	3/52 (5.8%)	4
Vaginal haemorrhage	18/56 (32.1%)	63	21/52 (40.4%)	151
Respiratory, thoracic and mediastinal disorders
Cough	3/56 (5.4%)	4	3/52 (5.8%)	3
Oropharyngeal pain	4/56 (7.1%)	4	5/52 (9.6%)	8
Skin and subcutaneous tissue disorders
Acne	18/56 (32.1%)	32	11/52 (21.2%)	22
Rash	3/56 (5.4%)	5	0/52 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.