A Pilot Prospective, Randomized Pharmacodynamic Study With Assessment of Ulipristal Acetate on Ovarian Activity Following Quickstart of the Etonogestrel Contraceptive Implant
Phase: EARLY_PHASE1
Conditions: Contraception
Sponsor: University of Utah

 
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Study Title: 
 
A pilot prospective, randomized pharmacodynamic study with assessment of ulipristal 
acetate on ovarian activity following quickstart of the etonogestrel contraceptive 
implant  
 
Institution Name 
University of Utah  
Investigator  
­  
 
Principal Investigator: Lori Gawron, MD, MPH 
 
NCT Number 
NCT04291001 
Document Date 
Jan 12, 2024 
 
 
 

 
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Protocol 
 
Study Design 
 
Study design: Pilot randomized, single site clinical trial with blinded analysis 
 
Participant recruitment and study site: We will recruit participants interested in using 
the ENG contraceptive implant but not currently at risk for pregnancy from University 
of Utah Hospital and Community clinics, and through targeted social media ads. All 
study procedures will occur at the University of Utah Hospital Outpatient OBGYN 
Clinic 
 
Sample size: This is a pilot proposal to recruit a total of 40 participants across 2 
study arms: (1) ENG implant only (n=20) and (2) UPA + same day ENG implant 
insertion (n=20). Our null hypotheses are: 
1)  ENG implant along with UPA administration in the presence of a dominant 
ovarian follicle will not change the expected 97% ovulation suppression within 5 days 
of UPA use.  
2)  ENG implant insertion alone in the presence of a dominant ovarian follicle will not 
sufficiently interrupt ovulation.  
 
Inclusion criteria: Healthy people, age 18-35 years, fluent in English and/or Spanish, 
BMI < 30 kg/m2, no known contraindication to either the ENG contraceptive implant 
or UPA using the CDC Medical Eligibility Criteria for Contraceptive Use 2016, not 
currently pregnant and not at risk of pregnancy (defined as not having penile-vaginal 
intercourse or using a non-hormonal method of contraception such as a barrier 
method, condoms, diaphragm, or cervical cap, a copper IUD, or permanent 
contraception), know the date of their last menstrual period, have a regular 
menstrual cycle (24-35 days), be willing to comply with the study requirements, and 
be willing to avoid pregnancy for study duration. 
 
Exclusion criteria: Current pregnancy or breastfeeding, use of hormonal 
contraception or exogenous hormones (estrogen, progestogen, or HCG) in the last 
month (or past 6 months for depo medroxyprogesterone acetate) planned use during 
the study, vaginal bleeding of unknown etiology, allergy to UPA or ENG, regular or 
planned use of glucocorticoids during the study, or current or planned use of any 
medication that potentially interacts with UPA or ENG.  
 
Participant adherence: Screening protocol will ensure willingness to comply with all 
study procedures. Participants will receive compensation for each component of the 
protocol. 
 

 
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Study Flowchart 
 
Study Procedures 
Randomization scheme: block randomization with block size of 4 
 
Blinding protocol: This study will not be blinded as a pilot. The feasibility of the study, 
including clinic space limitations and provider time, relies on the same healthcare 
provider for implant insertion and ultrasound in many patients. All statistical analyses 
will be blinded to the statistician.  
 
Participant procedures:  
Screening Visit (Screening Visit 1): Subjects will be screened for eligibility and 
interest in the study. Each subject will have the study explained and, if they desire to 
participate, she will sign the informed consent prior to any study procedures. The 
screening visit will include: review of medical, surgical and social history, 
medications, menstrual dating, sexual history and contraceptive use, physical exam, 
including breast and pelvic, and a transvaginal ultrasound to ensure ability to 
document ovarian follicular activity in the treatment cycle. 
 
Progesterone Visit (Screening Visit 2): This brief visit will occur on days 20-24 of the 
menstrual cycle and may be combined with the screening visit (Visit 1) if the 
timeframe is met. This visit will include a review of any interim changes (if completed 
separate from the screening visit) in history, medications, pregnancy 
risk/contraception, and a serum progesterone level will be drawn. The participants 
will notify the study coordinator of the 1st day of their next menses. 
 
Ovarian monitoring (Screening Visits 3-7 +/- 2 visits): Participants will undergo 
transvaginal ultrasound evaluation of their ovaries three times a week starting on 
cycle day #7 (+/- 2 days). If/ When we identify a lead follicle with a mean diameter of 
>13mm in at least 2 dimensions, we will switch to daily monitoring.  
 
Treatment Day #1 (Treatment Visit #1): Once a lead follicle (≥14mm) is identified 
then participants will be randomized to one of two treatment groups: 
1) ENG implant insertion 
2) UPA 30mg PO tablet and same-day ENG implant insertion 
Assigned treatment will be administered (UPA and/or ENG implant insertion). We will 
obtain serum progesterone, LH levels, and estradiol levels. 
 
Treatment Days #2-8 (Treatment Visits #2-8): Participants will follow up daily for 
Days 2-8. Each day we will obtain transvaginal ultrasound measurement of ovarian 
follicle size, serum progesterone, LH levels, and estradiol levels. We will obtain daily 

 
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transvaginal ultrasounds until either follicle rupture is documented, the follicle is <12 
mm on two consecutive visits, or Day 8 ultrasound occurs (7 days after implant 
insertion), whichever occurs first.  
 
Treatment Day #14 (Exit Visit): Repeat ultrasound will occur on Day 14 following 
ENG implant insertion, and this will be the exit visit. 
 
Data collection: Source documents for each participant and visit number will be 
completed by the study personnel at the time of the visit. Form development, data 
collection, and data management will occur in RedCAP, secure web platform for 
building and managing online databases and surveys. Source documents 
maintained in individual participant binders. 
 
Assessing and reporting adverse events: The reporting period for AEs is the period 
immediately following the subject signing the informed consent through the 30 days 
following the final study visit. Each visit will include assessment of how the 
participant felt since the last visit, review of adverse event reports, implant insertion 
site reactions, lab results, and vital signs and physical exam findings. AEs will not be 
reported for screen failures unless a SAE is experienced during screening. For all 
AEs, the investigator will pursue and obtain information adequate to determine the 
outcome of the AE and to assess whether it met criteria for a SAE. Participants who 
have ongoing AEs or SAEs will be followed until resolution or stabilization or referred 
for additional care. AEs will be documented both on source documents and in the 
clinical database with SAEs reported per IRB guidelines. Participants will be 
provided instructions for contacting the study site to report any untoward medical 
occurrences. With permission from the participant, whenever possible records from 
all non-study medical providers related to medical occurrences will be obtained for 
review. AEs and SAEs will be reviewed by the Data Safety Monitoring Board as 
below (section 2.9). 
Statistical Analysis 
Plan 
The investigator and study team will be responsible for analyzing the study data. The 
official clinical database in RedCAP will not be analyzed until medical/scientific review 
has been completed, protocol violators have been identified (if appropriate), and data 
has been declared complete. 
Variables/Time Points of Interest 
The primary outcome is delay in rupture of the dominant follicle by 5 days (yes/no) 
between group 1 (ENG implant alone) and group 2 (UPA with same day ENG implant). 
If the date of follicle rupture was unclear by ultrasound alone, we will utilize serum 
hormone levels to adjudicate day of rupture. These measures include day of follicle 
collapse, day and value of highest LH, day and value of highest progesterone level. 
We will use an estradiol level of >100pg/ml to confirm the enlarged follicle is the 
dominant follicle on the treatment day. 
 
Statistical Methods 
The primary and secondary dichotomous outcome measures of ovulation by 5 days 
will be assessed by Wilcoxon sign rank test and demographic will be analyzed using 
descriptive statistics.  
 
Power/Sample Size: 
This is a pilot study to obtain point estimates for future study proposals. Current data 
on ovulatory function with mid-cycle implant insertion or the pharmacodynamics 
interactions between same day UPA and ENG are lacking.