Ethylvinyl Acetate (EVA) Vaginal Ring Delivery System Study (VaginalRing)
Inducing a Medical Castration With a GnRH Agonist While Simultaneously Replacing Physiologic Levels and Patterns of Human Sex Steroid Hormones Using an Ethylvinyl Acetate (EVA) Vaginal Ring Delivery System
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
3-Day Study (outpatient)
Healthy normal volunteers will participate in a 3-day outpatient study that will begin between days 1-7 of their menstrual cycle (i.e. early follicular phase). A negative urinary hCG will be obtained in these women prior to their starting the 3-day study. On the first day, subjects will have 4 baseline blood samples of 5mL each drawn at 20-minute intervals over an hour (Time = 0, +20, +40, +60). These will be pooled and will represent the pretreatment determination of gonadotropins and sex steroid levels. Thereafter, the individual vaginal rings to be tested will be inserted. Over the ensuing 3 days, subjects will have 3 blood draws per day (at approximately 8-9 AM, 12-1PM, and 4-5PM).
Serum levels of LH, FSH, E2, and P will be determined at the above time points for the next 3 days. A repeat CBC and LFT's will be done with the final blood draw. The only exceptions to this protocol will be those patients with the Sex Steroid Only rings in whom 75 ug/kg of a GnRH antagonist (Acyline IND# 58,448) will be administered subcutaneously every other day and upon subsequent onset of menses, subjects will return during day 3-6 for repeat LFT's and gonadotropins. This will ensure the return of normal liver function and hormonal levels.
A visual vaginal examination and colposcopy will be done at baseline and at the time of the removal of the ring. If lesions or abrasions are found at study termination, subjects will be followed until the lesions resolve. For the initial 3-day studies, daily visual inspection of the vaginal tissues will be conducted and findings recorded in a standardized manner.
The schedule of more intensive early sampling is selected to be certain that no rapid release of medication occurs from the rings during the earliest phase following their insertion. This will also document that we have, in fact, achieved a steady state of release of the ring's content in the circulation prior to expanding the duration of these studies to 14 days in the second portion of part A.
14 Day Study (14-Day Outpatient + 36-hour Inpatient)
Healthy normal volunteers will participate in a 14-day study that will begin between days 1-7 of their menstrual cycle (i.e. early follicular phase). A negative urinary hCG will be obtained in these women prior to their starting the 14-day study. On the first day, subjects will have 4 baseline blood samples of 5mL each drawn at 20-minute intervals over an hour (Time = 0, +20, +40, +60). These will be pooled and will represent the pretreatment determination of gonadotropins and sex steroid levels.
The individual vaginal rings to be tested will then be inserted. Subjects will return each day for the next 13 days between 8am and 12pm to the General Clinical Research Center to have 5mL of blood drawn to measure serum levels of LH, FSH, E2, and P. On day 14, the vaginal ring will be removed.
A visual vaginal examination and colposcopy will be done at baseline and at the time of the removal of the ring. If lesions or abrasions are found at study termination, subjects will be followed until the lesions resolve. For the initial 14-day studies, visual inspection of the vaginal tissues will be conducted at least 3 times per week and findings recorded in a standardized manner.
Two days later, subjects will be admitted to the General Clinical Research Center between the hours of 8am and 12pm for a 36-hour inpatient stay. Subjects will be given a 240 ug dose of the GnRH agonist intravenously and the subject's bloods drawn for GnRHa determinations at 0, 15, 30, 60, 75, 90, 120min, and then hourly for the remaining 36 hours. A repeat cbc will be drawn with the final blood draw.
These determinations will then be compared to the GnRH agonist determinations from the vaginal route of delivery during the previous 14 days and hence the % absorption of the GnRHa from the vagina.
The exceptions to this protocol will be those patients with the Sex Steroid Only rings in whom 75 ug/kg of a GnRH antagonist (Acyline IND# 58,448) will be administered subcutaneously every other day for the course of the 14 days. These subjects will not undergo the inpatient stay after the ring is removed. Repeat LFT's will be drawn with the final blood draw as well. Anytime the Acyline injection is given, subjects will be monitored for at least 30 minutes after each injection for signs/symptoms of an allergic reaction. Upon subsequent onset of menses, subjects will return during days 3-6 for repeat LFT's and gonadotropins. This will ensure the return of normal liver function and hormonal levels.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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-
Massachusetts
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Boston, Massachusetts, United States, 02115
- Clinical Unit for Research Trials In Skin (CURTIS)
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- A history of normal regular menstrual cycles (25-35 days);
- A normal physical examination;
- A body mass index (BMI) between 19 & 29
- A normal CBC, normal Prolactin level, normal LFT's
- A negative urinary hCG at the initiation of each study; and
- An agreement to refrain from attempting to conceive during the experimental cycle and the cycle thereafter by either abstinence and/or use of a barrier method of contraception.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: A
|
Ethylvinyl Acetate (EVA) Vaginal Ring Delivery System
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Serum Leuprolide Levels After EVA Ring Transvaginal Drug Delivery System Insertion
Time Frame: 8 hours
|
8 hours
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Alexandra B. Kimball, MD, MPH, Massachusetts General Hospital
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- 2004-P-001343
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