Contraception
Conditions
Keywords
Birth Control, Pregnancy Prevention, Contraceptive
Brief summary
Study of the contraceptive efficacy, cycle control, safety, and tolerability of MR-100A-01 in approxmiately 1200 women for up to 13 cycles
Detailed description
MR-100A-01 is a TDS of norelgestromin 4.86 mg/ethinyl estradiol 0.264 mg. This study will evaluate the contraceptive efficacy, cycle control, safety, and tolerability of MR-100A-01.
Interventions
DRUGMR-100A-01
Transdermal contraceptive delivery system
Sponsors
Mylan Technologies Inc.
Mylan Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
16 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Healthy, post-menarcheal and premenopausal women at risk of pregnancy who are at least 16 years of age with no upper age limit. Post-menarcheal female subjects who are at risk of pregnancy, and \<18 years are eligible provided that: 1. Applicable national, state, and local laws allow the subject to consent to sexual intercourse, 2. Applicable national, state, and local laws allow subjects in this age group to consent/assent to receive contraceptive services, and 3. All applicable laws and regulations regarding the informed consent/assent of the subjects to participate in clinical trials are observed. 2. Desires to avoid pregnancy, is seeking to use hormonal contraception for at least 1 year. 3. Has negative UPT results at screening and at enrollment visits. 4. Has normal, regular menstrual cycles that are between 21 and 35 days. 5. Engages in regular heterosexual vaginal intercourse. 6. Agrees not to use other contraceptives or other methodology to prevent pregnancy during the study. 7. Able to understand and voluntarily provide written informed consent or assent to participate in the study. 8. Able to understand and willing to be compliant with study procedures. 9. Willing to accept a risk of pregnancy. 10. Has demonstrated ability to complete e-Diary. 11. Planning to reside within a reasonable driving/ public transport distance of the research site (approximately 150 miles) for around 12 months (13 cycles).
Exclusion criteria
1. Known or suspected pregnancy or planning pregnancy during next 12 months. 2. Subjects with known hypersensitivity or intolerance to estrogens, progestins, or any components of the MR-100A-01 product. 3. History or presence of dermal sensitivity to topical applications including bandages, surgical tape. 4. Known infertility (current or known history) or history of sterilization in either partner. 5. Received injectable hormonal contraceptive therapy within 10 months of study enrollment or has had less than 2 consecutive, spontaneous menses after an injectable hormonal contraceptive was received at least 10 months earlier. 6. Current use of hormonal contraceptive implants (still implanted; or if an implant was removed, less than 3 consecutive spontaneous menses have occurred between removal and enrollment). 7. Has non-hormonal or hormonal intrauterine device (IUD) in place or has had a recent IUD removal without one spontaneous menses after removal prior to the date of enrollment. 8. Recent surgical or medical abortion, miscarriage, ectopic pregnancy, or vaginal or cesarean delivery and have had less than 3 consecutive, spontaneous menses or withdrawal bleeding episodes prior to enrollment. 9. Subjects lactating at the time of screening into the study. 10. Anticipates routine use of condoms or any other form of back-up contraception for protection from sexually transmitted infections during the study or for emergency contraception. 11. Subjects having a known contraindication to combined hormonal contraception as listed below: 1. Smoker who is ≥35 years old. 2. History or presence of ischemic heart disease, coronary artery disease, myocardial infarction, stroke, other cerebrovascular diseases including transient ischemic attacks (TIAs), valvular heart disease with complications (pulmonary hypertension, risk for atrial fibrillation, or history of subacute bacterial endocarditis), peripartum cardiomyopathy. 3. History or presence of hypertension (including adequately controlled hypertension) or hypertension with vascular disease or elevated blood pressure (BP) defined as systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg, measured in sitting position after 5 minutes of rest, considering the average of two readings measured 1 to 2 minutes apart 4. History or presence of deep vein thrombosis/pulmonary embolism (DVT/PE) or superficial venous thrombosis. 5. Has any comorbid condition that may require major surgery with prolonged immobilization during the study period. 6. Subjects with known inherited or acquired hypercoagulopathy. 7. History or presence of systemic lupus erythematosus. 8. History or presence of neurological conditions including migraine with aura at any age, migraine without aura in women ≥35 years age or in women who smoke, or multiple sclerosis with prolonged immobility. 9. History or presence of or suspected carcinoma of breast. 10. Has diabetes mellitus with nephropathy, retinopathy, neuropathy, or other vascular disease or diabetes of \>20 years' duration. 11. Has inflammatory bowel disease (ulcerative colitis or Crohn's disease) who are at increased risk for VTE 12. Medically treated or presence of symptomatic gall bladder disease. 13. History of combined hormonal contraceptive/pregnancy-related cholestasis/jaundice. 14. Presence of liver disease. 15. History of organ transplantation within 5 years before screening or chronic disease potentially necessitating organ transplantation during the anticipated course of the study. 16. Subject has requirement to be on treatment with medications prohibited during study. 12. Known or suspected estrogen or progestin sensitive malignant or premalignant conditions. 13. History of any other condition that in the Investigator's opinion suggests an elevated risk of arterial or venous thromboembolic disease. 14. Has uncontrolled thyroid disorder. 15. Has diagnosis of hereditary angioedema. 16. Has hyperlipidemia on screening. 17. Has uncontrolled diabetes mellitus. 18. Subjects with abnormal significant liver function tests. 19. Has a significantly abnormal cervical cancer screening test (cervical cytology with reflex human-papilloma-virus (HPV) testing or with HPV co-testing) performed at screening visit (for subjects aged ≥21 years) i.e., cervical dysplasia or invasive cervical cancer or has any abnormal cytology with/without HPV testing during 6 months prior to screening which may require additional screening or treatment during the study period 20. Subjects with chlamydial or gonorrheal infection. 21. Has unexplained vaginal bleeding. 22. History of known or suspected hepatitis B or C infection or high risk for sexually transmitted disease (STD). 23. Known human immunodeficiency virus (HIV) infection or positive confirmatory test at screening. 24. Current known active infection of coronavirus disease 2019 (COVID-19) or increased risk of COVID-19 related morbidity. Subjects who have had previous COVID-19 infections but have recovered by the time of enrollment visit may be enrolled if there are no current COVID-19 symptoms; Subjects who had previously received COVID-19 vaccine may be enrolled irrespective of the timing of the vaccination. 25. Within the past year, either history of suicidal ideation or attempt or severe depression requiring hospitalization. 26. Presence of any other concomitant disease or laboratory result that may worsen under hormonal treatment based on Investigator's discretion. 27. Positive urine drug screen. 28. Recent history (within prior 12 months) of drug or alcohol abuse or at Investigator discretion, history greater than 12 months prior and at risk for noncompliance. Current or recent history of (recreational or medicinal) marijuana use is not exclusionary at the investigator's discretion upon assessment of any potential risk. 29. Participation in an investigational study within 30 days prior to enrollment or intention to participate within next 13 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Contraceptive Efficacy of MR-100A-01 When Used Over Thirteen 28-day Cycles in Healthy, Post-menarcheal, Premenopausal, Heterosexually Active Female Subjects of Childbearing Potential Who Are at Least 16 Years of Age and at Risk of Pregnancy | approximately 12 months (13 cycles with each cycle for 4 weeks) | The Pearl Index, defined as the number of pregnancies per 100 women years, was calculated as: Pearl Index = (1300×number of on-treatment pregnancies)/number of evaluable cycles. Evaluable cycles were defined as the complete or incomplete 28-day cycles in which vaginal intercourse occurred and in which no back-up contraception was used based on the electronic diary data, unless a pregnancy occurred in such a cycle. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Probability of Pregnancy at the End of Cycle 13 | approximately 12 months (13 cycles with each cycle for 4 weeks) | Cumulative pregnancy rates over 1 year evaluated using life table analysis |
| Method Failure Pearl Index (PI) | approximately 12 months (13 cycles with each cycle for 4 weeks) | The method failure PI is defined as PI among all complete or incomplete on therapy cycles in which intercourse occurred and protocol guidelines for patch applications were appropriately followed and without any major protocol deviations |
| Incidence of Treatment Emergent Adverse Events (TEAEs) | approximately 12 months (13 cycles with each cycle for 4 weeks) | A summary of the count and percentage of subjects (2%) reporting a TEAE |
| Incidence of Serious Adverse Events (SAEs) | approximately 12 months (13 cycles with each cycle for 4 weeks) | A summary of count and percentage of subjects reporting a Treatment emergent SAE |
| Number of Participants Reported Application Site Disorder | approximately 12 months (13 cycles with each cycle for 4 weeks) | Number of participants reported Application site disorder which were treatment emergent adverse events (TEAE) |
| Number of Days of Unscheduled Bleeding/and or Spotting | approximately 12 months (13 cycles with each cycle for 4 weeks) | The observed number of days of unscheduled bleeding/and or spotting |
| Number of Bleeding and/or Spotting Episodes | approximately 12 months (13 cycles with each cycle for 4 weeks) | Number of Bleeding and/or Spotting episodes |
| Proportion of Subjects Reporting Unscheduled Bleeding/and or Spotting Episodes | approximately 12 months (13 cycles with each cycle for 4 weeks) | Incidences (percentage of subjects) of unscheduled bleeding and/or spotting episodes within each cycle |
| Adhesion Performance as Measured by Adhesion Scores [Patch Adhesion] | approximately 12 months (13 cycles with each cycle for 4 weeks) | The descriptive figures of adhesion performance reported by subjects in their e-Diary on all days except during the patch-free week on the following 5-point scale. Score 0 indicates best adhesion and score 4 indicates worst adhesion. Higher score indicates poor adhesion. Self-Reported Scoring System of Patch Adhesion Assessment Score 0 - The patch has essentially no lift off the skin (≥90% adhered) Score 1 - Only some edges of the patch lift off the skin (≥75% to \<90% adhered) Score 2 - Less than half of the patch lifts off the skin (≥50% to \<75% adhered) Score 3 - The patch is not detached, but more than half of it lifts off the skin without falling off (\>0% to \<50% adhered) Score 4 - The patch is detached and is completely off the skin (0% adhered) |
Countries
Canada, Puerto Rico, United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 27.8 years STANDARD_DEVIATION 6.5 |
| Body Mass Index <25 (kg/m2) | 592 Participants |
| Body Mass Index >=25 to <30 (kg/m2) | 547 Participants |
| Body Mass Index >=30 (kg/m2) | 133 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 567 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 705 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 15 Participants |
| Race (NIH/OMB) Asian | 88 Participants |
| Race (NIH/OMB) Black or African American | 272 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 39 Participants |
| Race (NIH/OMB) White | 855 Participants |
| Region of Enrollment Canada | 14 Participants |
| Region of Enrollment Puerto Rico | 7 Participants |
| Region of Enrollment United States | 1251 Participants |
| Sex: Female, Male Female | 1272 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1,272 |
| other Total, other adverse events | 388 / 1,272 |
| serious Total, serious adverse events | 16 / 1,272 |
Outcome results
None listed