A PK Study Comparing VeraCept vs. ParaGard Intrauterine Devices (IUDs)

Study Overview
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Brief Summary
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to Assess the Pharmacokinetic Properties of VeraCept™ Intrauterine Contraceptive vs ParaGard® in Healthy, Post- Menarcheal Women

Official Title
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A Randomized, Single-Blind, Comparative Bioavailability Study to Assess the Pharmacokinetic Properties of VeraCept™ Intrauterine Contraceptive vs ParaGard® in Healthy, Post-Menarcheal Women

Conditions
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Women at Risk for Pregnancy

Intervention / Treatment
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* Drug: VeraCept
* Drug: ParaGard


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Post-menarcheal, pre-menopausal females up to 45 years of age at the time of informed consent/assent and in good general health; History of regular menstrual cycles defined as occurring every 21-35 days when not using hormones or prior to recent pregnancy or spontaneous or induced abortion; Sexually active with a male partner who has not had a vasectomy; Reasonably expect to have coitus at least once monthly during the study period; In a mutually monogamous relationship of at least 3 months duration; Seeking to avoid pregnancy for the duration of the study; Willing to use the study drug as the sole form of contraception; Willing to accept a risk of pregnancy; Subjects who are age 21 or older, at time of informed consent, must have a normal papanicolaou test (Pap) or atypical squamous cells of undetermined significance (ASC-US) with negative high risk human papilloma virus (HPV) test result within the appropriate screen timeframe per American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines, and prior to the study IUD insertion. Alternatively, the subject must have had a colposcopy performed within the appropriate screen timeframe, and prior to the study IUD insertion that showed no evidence of dysplasia requiring treatment per ASCCP guidelines, or treatment was performed and follow-up at least 6 months after the treatment showed no evidence of disease by clinical evaluation; Able and willing to comply with all study tests, procedures, assessment tools and follow-up; Able and willing to provide and document informed consent and Authorization for Release of Protected Health Information (PHI). Unemancipated subjects under 18 years old must provide assent and have written parental consent documented on the consent form consistent with local legal requirements; Plan to reside within a reasonable driving distance of a research site for the duration of the study. Subject agrees not to self-remove VeraCept Exclusion Criteria: Known or suspected pregnancy; or at risk for pregnancy from unprotected intercourse earlier in current cycle; A previously inserted intrauterine device (IUD) that has not been removed by the time the study IUD is placed; History of previous IUD complications, such as perforation, expulsion, or pregnancy with IUD in place; Pain with current IUD; Use of ParaGard IUD within the past 3 months Planned use of any non-contraceptive estrogen, progesterone or testosterone any time during the 60 months of study participation; Exclusively breastfeeding before return of menses; lactating women will be excluded unless they have had 2 normal menstrual periods prior to enrollment; Unexplained abnormal uterine bleeding (suspicious for a serious condition), including bleeding 4 weeks post-septic abortion or puerperal sepsis; Severely heavy or painful menstrual bleeding; Suspected or known cervical, uterine or ovarian cancer, or unresolved clinically significant abnormal Pap smear requiring evaluation or treatment; Any history of gestational trophoblastic disease with or without detectable elevated ß-human chorionic gonadotropin (ß-hCG) levels, or related malignant disease; Any congenital or acquired uterine anomaly that may complicate study drug placement, such as: Submucosal uterine leiomyoma Asherman's syndromes Pedunculated polyps Bicornuate uterus Didelphus or uterine septa Any distortions of the uterine cavity (e.g. fibroids), that, in the opinion of the investigator, are likely to cause issues during insertion, retention or removal of the IUD; Untreated acute cervicitis or vaginitis within the past 3 months; Known or suspected human immunodeficiency virus (HIV) infection or clinical AIDS; Subjects who have an established immunodeficiency; Known intolerance or allergy to any components of VeraCept or ParaGard including intolerance or allergy to nickel, titanium, or copper, and including Wilson's Disease; Currently participating or planning future participation in a research study of an investigational drug or device during the course of this investigational study. Subject must have waited at least 30 days from exiting their last study prior to informed consent in this study; Subject has been enrolled in a previous VeraCept study; Known or suspected alcohol or drug abuse within 12 months prior to the screening visit; Any general health, mental health or behavioral condition that, in the opinion of the investigator, could represent an increased risk for the subject or would render the subject less likely to provide the needed study information; Study staff or a member of the immediate family of study staff. Concurrent use of corticosteroids

Ages Eligible for Study
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Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VeraCept<br>VeraCept subjects will be inserted with VeraCept on Day 1. At Day 57 subjects will be informed that they received VeraCept and may continue in the study for up to 5 years | Drug: VeraCept<br>* VeraCept Intrauterine Device (IUD)<br>|
| Active Comparator: ParaGard<br>ParaGard subjects will be inserted with ParaGard on Day 1. At Day 57 subjects will be informed that they received ParaGard and may choose to have the ParaGard removed or continue use per standard of clinical care. | Drug: ParaGard<br>* ParaGard intrauterine copper contraceptive<br>* Other names: ParaGard T 380A;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Observed systemic copper bioavailability of VeraCept vs. ParaGard | Assess the relative bioavailability of observed systemic copper from VeraCept versus ParaGard based on Cmax | through Day 56 | 
| Observed systemic copper bioavailability of VeraCept vs. ParaGard | Assess the relative bioavailability of observed systemic copper from VeraCept versus ParaGard based on Cmean | through Day 56 | 
| Observed systemic copper bioavailability of VeraCept vs. ParaGard | Assess the relative bioavailability of observed systemic copper from VeraCept versus ParaGard based on Area Under the Curve (AUC)0-56 days | through Day 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline-corrected total serum copper of VeraCept vs. ParaGard | To assess the relative bioavailability of baseline-corrected total serum copper from the VeraCept IUD versus ParaGard based on Cmax | through Day 56 | 
| Baseline-corrected total serum copper of VeraCept vs. ParaGard | To assess the relative bioavailability of baseline-corrected total serum copper from the VeraCept IUD versus ParaGard based on Cmean | through Day 56 | 
| Baseline-corrected total serum copper of VeraCept vs. ParaGard | To assess the relative bioavailability of baseline-corrected total serum copper from the VeraCept IUD versus ParaGard based on AUC0-56 days | through Day 56 | 
| Compare total serum copper levels of VeraCept vs. ParaGard compared to normal copper levels | To assess the total serum copper levels within each treatment relative to the normal range (49 to 184 µg/dL). | through Day 56 for ParaGard and through Year-5 for VeraCept | 
| Long-term stability of copper levels as determined by Cmax - VeraCept only | To assess the long-term stability of copper levels following insertion of the VeraCept IUD | At Year 3 and Year 5 as determined by PK samples drawn at each visit |