A Multicenter Trial to Evaluate the Insertion Characteristics of the Radiopaque Etonogestrel Implant Using a Next Generation Applicator (34530)(P05702)
Study Details
Study Description
Brief Summary
The primary purpose of this study is to evaluate the use of the next generation applicator and its instructions for proper insertion of the Radiopaque Implant. Secondary objectives include: evaluation of implant removal, evaluation of the overall contraceptive efficacy and safety of the Radiopaque Implant, assessment of x -ray visibility of the Radiopaque Implant, and to assess participant expectations and satisfaction with the Radiopaque Implant.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Radiopaque Etonogestrel Implant Radiopaque Etonogestrel Implant (drug) inserted with the Next Generation Applicator (NGA) The Radiopaque Implant is a single rod contraceptive implant of 4 cm length and 2 mm in diameter which is placed at the inner side of the non-dominant upper-arm about 8-10 cm above the medial epicondyle. The Radiopaque Implant contains approximately 68 mg etonogestrel (ENG) dispersed in a matrix of ethylene vinyl acetate (EVA) copolymer and barium sulfate, surrounded by an EVA membrane. The barium-sulfate provides radio-opacity and allows detection by X-ray. The ENG dose released from the implant amounts to about 60-70 mcg/day shortly after insertion and decreases to about 40 mcg/day at the start of the second year, and to about 25-30 mcg/day at the end of the third year. |
Drug: Radiopaque Etonogestrel Implant
One implant inserted for a 3-year treatment period
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Applicator Users Who Were Very Satisfied and Satisfied- User Satisfaction Questionnaire for Domain: Design & Technical Aspects [Day 1]
In order to evaluate efficacy and ease of use of the Next Generation Applicator (NGA), the investigator/applicator user (AU) completed a User Satisfaction Questionnaire on Day 1 after the 12th implant insertion. The domain, 'Design/technical aspects' consisted of five questions: fit of the applicator in the hand, size, weight, handling, and color of the applicator were assessed. The percentage of AUs who were very satisfied and satisfied was presented.
- Percentage of Applicator Users Who Were Very Satisfied and Satisfied- User Satisfaction Questionnaire for Domain: Functionality [Day 1]
In order to evaluate efficacy and ease of use of the NGA, the investigator/AU completed a User Satisfaction Questionnaire on Day 1 after the 12th implant insertion. The domain, 'Functionality' consisted of six questions assessing functionality of the needle. The percentage of AUs who were very satisfied and satisfied was presented.
- Percentage of Applicator Users Who Were Very Satisfied and Satisfied- User Satisfaction Questionnaire by Domain: Safety [Day 1]
In order to evaluate efficacy and ease of use of the NGA, the investigator/AU completed a User Satisfaction Questionnaire on Day 1 after the 12th implant insertion. The domain, 'Safety' consisted of three questions: removal of the protection cap from applicator, full retraction of the needle into the applicator after insertion, difference in colors of the obturator & the implant. The percentage of AUs who were very satisfied and satisfied was presented.
- Percentage of Applicator Users Who Were Very Satisfied and Satisfied- User Satisfaction Questionnaire for Domain: Used Time [Day 1]
In order to evaluate efficacy and ease of use of the NGA, the investigator/AU completed a User Satisfaction Questionnaire on Day 1 after the 12th implant insertion. The domain, 'Used Time' consisted of one question: insertion time was assessed. The percentage of AUs who were very satisfied and satisfied was presented.
- Percentage of Applicator Users Who Were Very Satisfied and Satisfied- User Satisfaction Questionnaire for Domain: Applicator Satisfaction [Day 1]
In order to evaluate efficacy and ease of use of the NGA, the investigator/AU completed a User Satisfaction Questionnaire on Day 1 after the 12th implant insertion. The domain, 'Applicator Satisfaction' consisted of one question in order to assess the applicator. The percentage of AUs who were very satisfied and satisfied was presented.
- Implant Insertion Time (Seconds) [Day 1]
The implant insertion time was the time expressed in seconds, from removal of the protection cap from the applicator until retraction of the needle from the arm after insertion. Data was presented for overall investigators including experienced and non-experienced.
- Implant Removal Time (Seconds) [Day 1]
The implant removal time was the time expressed in seconds, from making the removal incision until placing the butterfly closure. Data was presented for overall investigators including experienced and non-experienced.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Woman of 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 <= 35 kg/m^2;
-
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 Radiopaque Implant.
-
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 Radiopaque Implant 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 Radiopaque Implant
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.- P05702
- 34530
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | At screening, a participant number was allocated to 308 participants of which 7 participants did not receive treatment. A total of 301 participants had an implant inserted. |
| Arm/Group Title | Radiopaque Etonogestrel Implant |
|---|---|
| Arm/Group Description | The Radiopaque Implant is a single rod contraceptive implant of 4 cm length and 2 mm in diameter which is placed at the inner side of the non-dominant upper-arm about 8-10 cm above the medial epicondyle. The Radiopaque Implant contains approximately 68 mg etonogestrel (ENG) dispersed in a matrix of ethylene vinyl acetate (EVA) copolymer and barium sulfate, surrounded by an EVA membrane. The barium-sulfate provides radio-opacity and allows detection by X-ray. The ENG dose released from the implant amounts to about 60-70 mcg/day shortly after insertion and decreases to about 40 mcg/day at the start of the second year, and to about 25-30 mcg/day at the end of the third year. |
| Period Title: Overall Study | |
| STARTED | 301 |
| COMPLETED | 156 |
| NOT COMPLETED | 145 |
Baseline Characteristics
| Arm/Group Title | Radiopaque Etonogestrel Implant |
|---|---|
| Arm/Group Description | The Radiopaque Implant is a single rod contraceptive implant of 4 cm length and 2 mm in diameter which is placed at the inner side of the non-dominant upper-arm about 8-10 cm above the medial epicondyle. The Radiopaque Implant contains approximately 68 mg etonogestrel (ENG) dispersed in a matrix of ethylene vinyl acetate (EVA) copolymer and barium sulfate, surrounded by an EVA membrane. The barium-sulfate provides radio-opacity and allows detection by X-ray. The ENG dose released from the implant amounts to about 60-70 mcg/day shortly after insertion and decreases to about 40 mcg/day at the start of the second year, and to about 25-30 mcg/day at the end of the third year. |
| Overall Participants | 301 |
| Age, Customized (participants) [Number] | |
| 18-20 years |
43
14.3%
|
| 21-25 years |
79
26.2%
|
| 26-30 years |
64
21.3%
|
| 31-35 years |
54
17.9%
|
| 36-40 years |
61
20.3%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
301
100%
|
| Male |
0
0%
|
Outcome Measures
| Title | Percentage of Applicator Users Who Were Very Satisfied and Satisfied- User Satisfaction Questionnaire for Domain: Design & Technical Aspects |
|---|---|
| Description | In order to evaluate efficacy and ease of use of the Next Generation Applicator (NGA), the investigator/applicator user (AU) completed a User Satisfaction Questionnaire on Day 1 after the 12th implant insertion. The domain, 'Design/technical aspects' consisted of five questions: fit of the applicator in the hand, size, weight, handling, and color of the applicator were assessed. The percentage of AUs who were very satisfied and satisfied was presented. |
| Time Frame | Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Applicator User (AU) group consisted of all investigators participating in the trial and who performed at least one insertion. |
| Arm/Group Title | Radiopaque Etonogestrel Implant |
|---|---|
| Arm/Group Description | The Radiopaque Implant is a single rod contraceptive implant of 4 cm length and 2 mm in diameter which is placed at the inner side of the non-dominant upper-arm about 8-10 cm above the medial epicondyle. The Radiopaque Implant contains approximately 68 mg etonogestrel (ENG) dispersed in a matrix of ethylene vinyl acetate (EVA) copolymer and barium sulfate, surrounded by an EVA membrane. The barium-sulfate provides radio-opacity and allows detection by X-ray. The ENG dose released from the implant amounts to about 60-70 mcg/day shortly after insertion and decreases to about 40 mcg/day at the start of the second year, and to about 25-30 mcg/day at the end of the third year. |
| Measure Participants | 23 |
| Number [Percentage of Applicator Users] |
99.1
|
| Title | Percentage of Applicator Users Who Were Very Satisfied and Satisfied- User Satisfaction Questionnaire for Domain: Functionality |
|---|---|
| Description | In order to evaluate efficacy and ease of use of the NGA, the investigator/AU completed a User Satisfaction Questionnaire on Day 1 after the 12th implant insertion. The domain, 'Functionality' consisted of six questions assessing functionality of the needle. The percentage of AUs who were very satisfied and satisfied was presented. |
| Time Frame | Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Applicator User (AU) group consisted of all investigators participating in the trial and who performed at least one insertion. |
| Arm/Group Title | Radiopaque Etonogestrel Implant |
|---|---|
| Arm/Group Description | The Radiopaque Implant is a single rod contraceptive implant of 4 cm length and 2 mm in diameter which is placed at the inner side of the non-dominant upper-arm about 8-10 cm above the medial epicondyle. The Radiopaque Implant contains approximately 68 mg etonogestrel (ENG) dispersed in a matrix of ethylene vinyl acetate (EVA) copolymer and barium sulfate, surrounded by an EVA membrane. The barium-sulfate provides radio-opacity and allows detection by X-ray. The ENG dose released from the implant amounts to about 60-70 mcg/day shortly after insertion and decreases to about 40 mcg/day at the start of the second year, and to about 25-30 mcg/day at the end of the third year. |
| Measure Participants | 23 |
| Number [Percentage of Applicator Users] |
94.9
|
| Title | Percentage of Applicator Users Who Were Very Satisfied and Satisfied- User Satisfaction Questionnaire by Domain: Safety |
|---|---|
| Description | In order to evaluate efficacy and ease of use of the NGA, the investigator/AU completed a User Satisfaction Questionnaire on Day 1 after the 12th implant insertion. The domain, 'Safety' consisted of three questions: removal of the protection cap from applicator, full retraction of the needle into the applicator after insertion, difference in colors of the obturator & the implant. The percentage of AUs who were very satisfied and satisfied was presented. |
| Time Frame | Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Applicator User (AU) group consisted of all investigators participating in the trial and who performed at least one insertion. |
| Arm/Group Title | Radiopaque Etonogestrel Implant |
|---|---|
| Arm/Group Description | The Radiopaque Implant is a single rod contraceptive implant of 4 cm length and 2 mm in diameter which is placed at the inner side of the non-dominant upper-arm about 8-10 cm above the medial epicondyle. The Radiopaque Implant contains approximately 68 mg etonogestrel (ENG) dispersed in a matrix of ethylene vinyl acetate (EVA) copolymer and barium sulfate, surrounded by an EVA membrane. The barium-sulfate provides radio-opacity and allows detection by X-ray. The ENG dose released from the implant amounts to about 60-70 mcg/day shortly after insertion and decreases to about 40 mcg/day at the start of the second year, and to about 25-30 mcg/day at the end of the third year. |
| Measure Participants | 23 |
| Number [Percentage of Applicator Users] |
98.6
|
| Title | Percentage of Applicator Users Who Were Very Satisfied and Satisfied- User Satisfaction Questionnaire for Domain: Used Time |
|---|---|
| Description | In order to evaluate efficacy and ease of use of the NGA, the investigator/AU completed a User Satisfaction Questionnaire on Day 1 after the 12th implant insertion. The domain, 'Used Time' consisted of one question: insertion time was assessed. The percentage of AUs who were very satisfied and satisfied was presented. |
| Time Frame | Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Applicator User (AU) group consisted of all investigators participating in the trial and who performed at least one insertion. |
| Arm/Group Title | Radiopaque Etonogestrel Implant |
|---|---|
| Arm/Group Description | The Radiopaque Implant is a single rod contraceptive implant of 4 cm length and 2 mm in diameter which is placed at the inner side of the non-dominant upper-arm about 8-10 cm above the medial epicondyle. The Radiopaque Implant contains approximately 68 mg etonogestrel (ENG) dispersed in a matrix of ethylene vinyl acetate (EVA) copolymer and barium sulfate, surrounded by an EVA membrane. The barium-sulfate provides radio-opacity and allows detection by X-ray. The ENG dose released from the implant amounts to about 60-70 mcg/day shortly after insertion and decreases to about 40 mcg/day at the start of the second year, and to about 25-30 mcg/day at the end of the third year. |
| Measure Participants | 23 |
| Number [Percentage of Applicator Users] |
100
|
| Title | Percentage of Applicator Users Who Were Very Satisfied and Satisfied- User Satisfaction Questionnaire for Domain: Applicator Satisfaction |
|---|---|
| Description | In order to evaluate efficacy and ease of use of the NGA, the investigator/AU completed a User Satisfaction Questionnaire on Day 1 after the 12th implant insertion. The domain, 'Applicator Satisfaction' consisted of one question in order to assess the applicator. The percentage of AUs who were very satisfied and satisfied was presented. |
| Time Frame | Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Applicator User (AU) group consisted of all investigators participating in the trial and who performed at least one insertion. |
| Arm/Group Title | Radiopaque Etonogestrel Implant |
|---|---|
| Arm/Group Description | The Radiopaque Implant is a single rod contraceptive implant of 4 cm length and 2 mm in diameter which is placed at the inner side of the non-dominant upper-arm about 8-10 cm above the medial epicondyle. The Radiopaque Implant contains approximately 68 mg etonogestrel (ENG) dispersed in a matrix of ethylene vinyl acetate (EVA) copolymer and barium sulfate, surrounded by an EVA membrane. The barium-sulfate provides radio-opacity and allows detection by X-ray. The ENG dose released from the implant amounts to about 60-70 mcg/day shortly after insertion and decreases to about 40 mcg/day at the start of the second year, and to about 25-30 mcg/day at the end of the third year. |
| Measure Participants | 23 |
| Number [Percentage of Applicator Users] |
100
|
| Title | Implant Insertion Time (Seconds) |
|---|---|
| Description | The implant insertion time was the time expressed in seconds, from removal of the protection cap from the applicator until retraction of the needle from the arm after insertion. Data was presented for overall investigators including experienced and non-experienced. |
| Time Frame | Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-Subjects-Treated (AST) group included all participants who had the Radiopaque implant inserted (N=301). Data was reported for 291 implant insertions. |
| Arm/Group Title | Radiopaque Etonogestrel Implant |
|---|---|
| Arm/Group Description | The Radiopaque Implant is a single rod contraceptive implant of 4 cm length and 2 mm in diameter which is placed at the inner side of the non-dominant upper-arm about 8-10 cm above the medial epicondyle. The Radiopaque Implant contains approximately 68 mg etonogestrel (ENG) dispersed in a matrix of ethylene vinyl acetate (EVA) copolymer and barium sulfate, surrounded by an EVA membrane. The barium-sulfate provides radio-opacity and allows detection by X-ray. The ENG dose released from the implant amounts to about 60-70 mcg/day shortly after insertion and decreases to about 40 mcg/day at the start of the second year, and to about 25-30 mcg/day at the end of the third year. |
| Measure Participants | 291 |
| Mean (Standard Deviation) [Seconds] |
27.9
(29.3)
|
| Title | Implant Removal Time (Seconds) |
|---|---|
| Description | The implant removal time was the time expressed in seconds, from making the removal incision until placing the butterfly closure. Data was presented for overall investigators including experienced and non-experienced. |
| Time Frame | Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-Subjects-Treated (AST) group included all participants who had the Radiopaque implant inserted (N=301). Data was reported for 292 implant removals. |
| Arm/Group Title | Radiopaque Etonogestrel Implant |
|---|---|
| Arm/Group Description | The Radiopaque Implant is a single rod contraceptive implant of 4 cm length and 2 mm in diameter which is placed at the inner side of the non-dominant upper-arm about 8-10 cm above the medial epicondyle. The Radiopaque Implant contains approximately 68 mg etonogestrel (ENG) dispersed in a matrix of ethylene vinyl acetate (EVA) copolymer and barium sulfate, surrounded by an EVA membrane. The barium-sulfate provides radio-opacity and allows detection by X-ray. The ENG dose released from the implant amounts to about 60-70 mcg/day shortly after insertion and decreases to about 40 mcg/day at the start of the second year, and to about 25-30 mcg/day at the end of the third year. |
| Measure Participants | 292 |
| Mean (Standard Deviation) [Seconds] |
119.3
(120.2)
|
Adverse Events
| Time Frame | Safety data from the actual in-treatment period was used. The in-treatment period started on the day of the implant insertion and continued up to and including the fifth day after implant removal (3 years). | |
|---|---|---|
| Adverse Event Reporting Description | The safety analysis was performed for the AST group; all subjects who had the Radiopaque Implant inserted. | |
| Arm/Group Title | Radiopaque Etonogestrel Implant | |
| Arm/Group Description | The Radiopaque Implant is a single rod contraceptive implant of 4 cm length and 2 mm in diameter which is placed at the inner side of the non-dominant upper-arm about 8-10 cm above the medial epicondyle. The Radiopaque Implant contains approximately 68 mg etonogestrel (ENG) dispersed in a matrix of ethylene vinyl acetate (EVA) copolymer and barium sulfate, surrounded by an EVA membrane. The barium-sulfate provides radio-opacity and allows detection by X-ray. The ENG dose released from the implant amounts to about 60-70 mcg/day shortly after insertion and decreases to about 40 mcg/day at the start of the second year, and to about 25-30 mcg/day at the end of the third year. | |
All Cause Mortality |
||
| Radiopaque Etonogestrel Implant | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Radiopaque Etonogestrel Implant | ||
| Affected / at Risk (%) | # Events | |
| Total | 17/301 (5.6%) | |
| Gastrointestinal disorders | ||
| Abdominal Pain | 1/301 (0.3%) | 1 |
| Hepatobiliary disorders | ||
| Jaundice | 1/301 (0.3%) | 1 |
| Infections and infestations | ||
| Appendicitis | 2/301 (0.7%) | 2 |
| Campylobacter gastroenteritis | 1/301 (0.3%) | 1 |
| Salpingo-oophoritis | 1/301 (0.3%) | 1 |
| Metabolism and nutrition disorders | ||
| Hypoglycaemia | 1/301 (0.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Intervertebral disc protrusion | 1/301 (0.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Breast Cancer | 1/301 (0.3%) | 1 |
| Leiomyoma | 1/301 (0.3%) | 1 |
| Thyroid Cancer | 1/301 (0.3%) | 1 |
| Nervous system disorders | ||
| Lethargy | 1/301 (0.3%) | 1 |
| Migraine | 1/301 (0.3%) | 1 |
| Sciatica | 1/301 (0.3%) | 1 |
| Psychiatric disorders | ||
| Bipolar Disorder | 1/301 (0.3%) | 1 |
| Depression | 1/301 (0.3%) | 1 |
| Suicide Attempt | 1/301 (0.3%) | 1 |
| Renal and urinary disorders | ||
| Calculus Urinary | 1/301 (0.3%) | 1 |
| Reproductive system and breast disorders | ||
| Ovarian Cyst | 1/301 (0.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Radiopaque Etonogestrel Implant | ||
| Affected / at Risk (%) | # Events | |
| Total | 233/301 (77.4%) | |
| General disorders | ||
| Implant Site Haematoma | 16/301 (5.3%) | 16 |
| Implant Site Pain | 18/301 (6%) | 20 |
| Infections and infestations | ||
| Influenza | 19/301 (6.3%) | 22 |
| Nasopharyngitis | 32/301 (10.6%) | 45 |
| Upper Respiratory Tract Infection | 20/301 (6.6%) | 30 |
| Urinary Tract Infection | 20/301 (6.6%) | 31 |
| Vulvovaginal Candidiasis | 19/301 (6.3%) | 26 |
| Investigations | ||
| Weight Increased | 35/301 (11.6%) | 38 |
| Nervous system disorders | ||
| Headache | 56/301 (18.6%) | 103 |
| Reproductive system and breast disorders | ||
| Amenorrhoea | 21/301 (7%) | 23 |
| Dysmenorrhoea | 16/301 (5.3%) | 18 |
| Menorrhagia | 31/301 (10.3%) | 35 |
| Metrorrhagia | 53/301 (17.6%) | 60 |
| Vaginal Haemorrhage | 85/301 (28.2%) | 126 |
| Acne | 39/301 (13%) | 48 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
SPONSOR recognizes the right of the investigator(s) to publish, but all publications must be based on data validated and released by SPONSOR. Any such scientific paper, presentation, or other communication concerning the clinical trial described in protocol will first be submitted to SPONSOR, at least six weeks ahead of estimated publication or presentation, for written consent, which shall not be withheld unreasonably.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | |
| ClinicalTrialsDisclosure@merck.com |
- P05702
- 34530