Conditions: Obesity Contraception
Keywords: obesity body weight BMI emergency contraception levonorgestrel ulipristal acetate
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 64
Healthy volunteers: yes

Brief summary:
Obese women are significantly more likely than their normal BMI counterparts to experience failure of orally-dosed emergency contraceptives. Our preliminary data provides evidence for testing a dose escalation strategy in an effort to provide improved efficacy from orally-dosed emergency contraceptives in obese women. More data is needed regarding emergency contraception containing ulipristal acetate. The overall project will be focused on both levonorgestrel (LNG) - and ulipristal acetate (UPA)-containing emergency contraception but this protocol registration is for the UPA aspect of the study procedures.

Detailed description:
Emergency contraception (EC) provides a woman with an additional line of defense against unintended pregnancy following an act of unprotected intercourse. Orally-dosed EC works by delaying ovulation and reduces the risk of pregnancy for a single act of unprotected intercourse by 50-70%. Unfortunately, obese women are significantly more likely than their normal BMI counterparts to experience failure of orally-dosed EC and in some instances EC is equivalent to placebo.

Our preliminary data provides evidence for testing a dose escalation strategy in an effort to provide improved efficacy from orally-dosed EC in obese women. We hypothesize that increasing the dose of orally-dosed EC agents will normalize the pharmacokinetics resulting in the expected treatment effect (delay in follicle rupture) in obese women. In the overall proposal, we plan to perform detailed pharmacokinetic and pharmacodynamic studies of UPA-based EC in obese women and expand upon our preliminary findings of LNG-based EC. This protocol registration is for the UPA aspect of the study procedures focused on the pharmacokinetics and pharmacodynamics of UPA and will include a dose escalation intervention.

Arms:
arm 1: Ulipristal acetate 30mg orally x 1 dose, washout cycle and then in the next menstrual cycle, 60mg x 1 dose. Timing of dosage depends on follicle measurements. arm 2: Ulipristal acetate 60mg orally x 1 dose, washout cycle, and then in next menstrual cycle 30mg orally x 1 dose. Timing of dosage depends on follicle measurements. arm 3: Ulipristal acetate 30mg orally x 1 dose. timing of dosage depends on follicle measurements. This is to obtain a normal BMI control group.

Interventions: intervention 1: UPA-ECx1 intervention 2: UPA-ECx2
Intervention descriptions: intervention 1: Evaluating the pharmacodynamic and pharmacokinetic outcomes in obese women using 30mg of UPA-based EC intervention 2: Evaluating the pharmacodynamic and pharmacokinetic outcomes in obese women using 60mg of UPA-based EC

Protocol document:
ICF_001.pdf: 
 
 Version 3/1/2016 
 
Page 1 of 1 
 
 
IRB#: 16291 
 
 
MED. REC. NO. _____ 
NAME 
_____ 
BIRTHDATE 
_____ 
 
 
 
Clinical Research Consent Summary 
 
 
 
TITLE: Improving the effectiveness of orally dosed emergency contraceptives in women 
of varying weights/BMIs – Part 2. UPA EC, BMI > or = 30mg/k2 and weight > or =80kg and 
curtailed PK sampling 
 
PRINCIPAL INVESTIGATOR: 
Alison Edelman, MD, MPH             503-418-2585 
 
You are being asked to join a research study. You do not have to join the study.  Even if you 
decide to join now, you can change your mind later. 
 
1. The purpose of this research study is to determine how well an emergency contraceptive 
pill containing ulipristal acetate works in women of higher weight and body mass index 
(BMI) as compared to women of lower weight and body mass index. This type of 
emergency contraceptive is currently available only with a prescription. It is the most 
effective form of oral emergency contraception. There is concern that it may be less 
effective in women of higher weights and BMI. We want to learn more about the drug 
level differences and how the ovary responds in women of differing BMI and weight. The 
overall goal of this research is to improve the effectiveness of contraception for women, 
no matter their weight or BMI. 
 
2. The study drug is a tablet taken once by mouth. 
 
3. The study drug is approved by the U.S. Food and Drug administration (FDA) 
 
4. The National Institutes of Health is paying for the research study. 
 
5. If you agree to be a part of this study, your participation will last 5 months. This will 
include up to 33 visits to the clinic at Oregon Health & Science University (OHSU). The 
majority of these visits will include a blood draw as well as a vaginal ultrasound and will 
last approximately 30 minutes but two visits will last longer (2 hours). 
 
6.  Samples and information collected during the study may be saved for future research. 
 
 


 
 Version 3/1/2016 
 
Page 1 of 9 
 
 
 
 
IRB#: 16291 
 
 
 
MED. REC. NO. _____ 
NAME 
_____ 
BIRTHDATE 
_____ 
 
 
Clinical Research Consent and Authorization Form 
 
TITLE: Improving the effectiveness of orally dosed emergency contraceptives in women 
of varying weights/BMIs – Part 2. UPA EC, BMI > or = 30mg/k2 and weight > or =80kg and 
full PK sampling 
 
PRINCIPAL INVESTIGATOR: 
Alison Edelman, MD, MPH               503-418-2585 
 
CO-INVESTIGATORS: 
 
Paula Bednarek, MD, MPH 
503-418-2585         
 
Mark Nichols, MD 
503-418-2585 
 
Jeffrey Jensen, MD, MPH 
Maureen Baldwin, MD 
Eva Patil, MD 
Leo Han, MD 
503-418-2585 
503-418-2585 
503-494-2685 
503-494-2685 
 
Marci Messerle Forbes, FNP 
503-494-6151 
 
Andrea O’Donnell, FNP 
503-494-3131 
 
Maria Rodriguez, MD 
503-494-2685 
 
Jacqueline Lamme, MD 
503-494-2685 
 
Alyssa Colwill, MD                            503-494-2685 
 
 
 
 
 
     
 
FUNDED BY:  National Institutes of Health 
 
 
CONFLICT OF INTEREST:  The investigators involved in this study have no conflict of interests 
related to this research. 
 
PURPOSE:  The purpose of this research study is to determine the differences in drug level and 
ovulation in women of varying weight and body mass index (BMI) using an emergency 
contraceptive pill containing ulipristal acetate.  
 
This type of emergency contraceptive is currently available only with a prescription. It is the 
most effective form of oral emergency contraception. There is concern that it may be less 
effective in higher weights and BMI. We want to learn more about the drug level differences and 
how the ovary responds in women of differing BMI and weight. The overall goal of this research 
is to improve the effectiveness of contraception for women, no matter their weight or BMI. 
 
You have been invited to be in this research study because:  
1) You are between the ages of 18 and 35 
2) You are in good general health, have a body mass index (BMI) >30 and a weight >176 
lbs and the study medication are safe for you to take.  
3) You have regular menstrual cycles (between 21 and 35 days) 
4) You have been proven to be ovulatory 


 
 
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5) You are willing to use condoms (if you are sexually active with a male partner), you are 
willing to not have sex with men during the study, or you have had a tubal ligation (or 
have a partner who has had a vasectomy) or you have a copper IUD. 
 
If you agree to be a part of this study, your participation will last 5 months. This will include up to 
33 visits to the clinic at Oregon Health & Science University (OHSU). The majority of these visits 
will include a blood draw as well as a vaginal ultrasound and will last approximately 30 minutes 
but two visits will last longer and will include a series of blood sampling (2 hours). 
 
You will also be given information about being involved in another part of this study. If you agree 
to be involved in Part 1, you will be asked to sign a separate consent form. Your participation in 
Part 1 would include up to 13 additional visits over an additional 1 month of participation. Your 
total participation in both parts of the study would last approximately 6 months and included up 
to 46 visit.  
 
You do not have to join the study. Even if you decide to join now, you can change your mind 
later. 
 
We may have left over blood samples from you.  We are asking your permission to store these 
samples indefinitely in a blood and data bank (also called a repository) so that they may be 
used and disclose in the future for research.  We will not be performing genetic research on 
these samples.  
 
We plan to enroll up to 80 women in the study at OHSU. By signing this consent form, you are 
consenting to the 2 longer two hour visits. Additionally, if you have not already participated in 
Part 1 of this study, you may be eligible to do so but will need to sign the Part 1 consent form. 
 
PROCEDURES:   
 
If you agree to be in this study, you will be asked to give your consent by signing this form. 
Participation in this study will consist of up to 30 visits. The details of these visits are described 
below. Participation in this study involves a time commitment so please consider whether this 
will fit into your schedule. Some study visits may need occur on weekends or holidays 
depending on your cycle. 
 
At each of your study visits, study staff will review information regarding your last menstrual 
period, any medical concerns, and any medications you take as well as taking your vital signs. 
Your weight will be obtained at the beginning and end of the study. Prior to taking the study 
medication (UPA), a urine pregnancy test will be performed.   
 
At the majority of your study visits, you will have a blood sample taken and undergo a vaginal 
probe ultrasound to monitor your ovarian activity, specifically the development of a follicle (a 
normal occurring cyst) and ovulation (the release of the egg). Starting on cycle day 7-8, you will 
have visits every other day until you are given the study medication.  The medication will be 
given to you based on the size of your follicle (approximately cycle day 10). On the day you are 
given the medication, you will undergo more frequent blood sampling and must stay at the 
research unit for approximately 2 hours. Following this, you will have daily study visits for 7 days 
unless evidence of ovulation occurs earlier. You will have no visits for the remainder of this 
menstrual cycle but will be in contact with the study staff to notify them when your menstrual 
period starts. This will be the end of your study participation. 
 
V0 Screening visit (Luteal phase) 
At this visit, study staff will go over the consent form with you. You will have time to ask any 
questions you may have. After you have agreed to be in the study, study staff will take your 
complete medical and gynecologic history, including smoking history, documentation of 


 
 
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menstrual cycle history, current sexual activity and contraceptive method with dates of use, and 
information about pregnancies and childbirths. Study staff will also ask questions about your 
education, ethnicity/race, marital status, and alcohol or drug use. Expect the screening visit to 
take approximately 2 hours. 
• 
A general physical examination (including height, weight and body mass index, a ratio of 
your weight to height) will be performed. Blood pressure (BP) and pulse will be 
measured. 
• 
Blood will be drawn from a vein in your arm (about 2 teaspoons) to check your hormone 
(progesterone) levels. This blood test should occur between days 18-25 of your 
menstrual cycle. If this visit does not fall within that window, we will ask you to return to 
the clinic for this blood draw.  
 
Of note, if you already participated in Part 1 of this study, then you do not need to repeat 
this visit unless more than 12 months have passed. 
 
Cycle 1 V1-V6 (Control cycle) 
Starting on day 7-8 of your menstrual cycle, you will be seen every other day until 
documentation of an enlarged follicle where you will then be followed daily for 7 days unless 
evidence of ovulation occurs earlier or no development of an ovulatory follicle occurs. You will 
receive no study drug in this cycle, we are only monitoring how your normal cycle acts. If no 
evidence of an ovulatory follicle occurs, this will be the end of your study participation.  
 
At these visits, study staff will: 
 
• 
Take vital signs  
• 
Get urine for a pregnancy test (only at the visit where you receive study drug) 
• 
Update your medical and gynecological history, medications and allergies 
• 
Take blood samples to test your hormone levels. A total of 2 tablespoons of blood will be 
collected at each visit. 
• 
Perform a transvaginal ultrasound (TVUS) to examine your ovaries and monitor signs of 
ovulation. Before the procedure, you will be asked to empty your bladder. For the vaginal 
ultrasound, the tip of a small, thin ultrasound instrument (probe) is lubricated with a small 
amount of gel and inserted in your vagina. Only two to three inches of the instrument are 
inserted into the vagina. Ultrasound imaging uses sound waves to produce pictures of 
the inside of the uterus and ovaries.  The ultrasound pictures will be shown on a 
computer monitor. The provider will be looking at the thickness of the endometrium 
(lining of the womb), number of ovarian follicles (fluid filled sacs located just beneath the 
ovary’s surface that contain the immature eggs), and whether you have ovulated 
recently or are about to ovulate (release an egg). 
 
Each study visit will take approximately 30 minutes to complete. 
 
Cycle 2 V1-V13 (Treatment cycle) 
Starting on day 7-8 of your menstrual cycle, you will be seen every other day until 
documentation of an enlarged follicle where you will then take study drug. You will be followed 
daily for 7 days from the time you take the study drug unless evidence of ovulation occurs 
earlier or no development of an ovulatory follicle occurs. If no evidence of an ovulatory follicle 
occurs, this will be the end of your study participation.  
 
Expect these visits to take approximately 30 minutes. At these visits, study staff will: 
• 
Take vital signs  
• 
Get urine for a pregnancy test (only at the visit where you receive study drug) 
• 
Update your medical and gynecological history, medications and allergies 


 
 
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• 
Take blood samples to test your hormone levels that help determine ovulation. At total of 
2 tablespoon of blood will be collected at each visit. 
• 
Perform a transvaginal ultrasound (TVUS) to examine your ovaries and monitor signs of 
ovulation. 
 
On the day that you take the study drug, you will need to stay at the research unit for 2 
hours to obtain a series of blood draws. At this visit, study staff will:  
• 
Take vital signs  
• 
Get urine for a pregnancy test (only at the visit where you receive study drug) 
• 
Update your medical and gynecological history, medications and allergies 
• 
Perform a transvaginal ultrasound (TVUS) to examine your ovaries and monitor signs of 
ovulation. 
• 
Place an I.V. (intravenous access). You may also choose “single stick” venipuncture for 
each blood draw. 
• 
Provide you with study drug to take.  
Draw blood to test for study drug levels at 0.5, 1, 1.5, 24, 48, 72, 96, and 120 hours after the 
study drug has been taken.  A total of 4 tablespoons of blood will be collected in total. 
 
Cycle 3 Washout cycle 
No study visits will occur during this menstrual cycle but you will remain in contact with study 
staff, likely 1-2 times, by telephone or email for scheduling purposes and to discuss any health 
changes you are experiencing.  
 
Cycle 4 V1-V13 (Treatment cycle) 
Starting on day 7-8 of your menstrual cycle, you will be seen every other day until 
documentation of an enlarged follicle where you will then take study drug. You will be followed 
daily for 7 days from the time you take the study drug unless evidence of ovulation occurs 
earlier or no development of an ovulatory follicle occurs. If no evidence of an ovulatory follicle 
occurs, this will be the end of your study participation.  
 
Expect these visits to take approximately 30 minutes. At these visits, study staff will: 
• 
Take vital signs  
• 
Get urine for a pregnancy test (only at the visit where you receive study drug) 
• 
Update your medical and gynecological history, medications and allergies 
• 
Take blood samples to test your hormone levels that help determine ovulation. At total of 
2 tablespoon of blood will be collected at each visit. 
• 
Perform a transvaginal ultrasound (TVUS) to examine your ovaries and monitor signs of 
ovulation. 
 
On the day that you take the study drug, you will need to stay at the research unit for 2 
hours to obtain a series of blood draws. At this visit, study staff will:  
• 
Take vital signs  
• 
Get urine for a pregnancy test (only at the visit where you receive study drug) 
• 
Update your medical and gynecological history, medications and allergies 
• 
Perform a transvaginal ultrasound (TVUS) to examine your ovaries and monitor signs of 
ovulation. 
• 
Place an I.V. (intravenous access). You may also choose “single stick” venipuncture for 
each blood draw. 
• 
Provide you with study drug to take.  
Draw blood to test for study drug levels at 0.5, 1, 1.5, 24, 48, 72, 96, and 120 hours after the 
study drug has been taken.  A total of 4 tablespoons of blood will be collected in total. 
 
 
 


 
 
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*Visit number study medication will be taken depends on ultrasound findings. 
**The study visit on the day the study medication is taken will last 1 hours 
 
In the future, your blood sample and/or information may be used by the investigators in this 
research for other research studies. The samples and information will be labeled as described in 
the CONFIDENTIALITY section. 
 
ACCESS TO YOUR TEST RESULTS 
We do not plan to share your research test results with you or your primary care provider.  
However, if we discover information that is important for your health care, either in this study or 
in the future, we will contact you and ask if you want to know the results.  If you choose to 
receive the results, you may need to have the test repeated in a non-research laboratory.  You 
may learn information about your health that is upsetting or that impacts your future birth control 
choices or your future fertility.  
 
RISKS AND DISCOMFORTS:  
 
Ulipristal Acetate (UPA) 
All medicines may cause side effects, but many people have no side effects or minor side 
effects. The use of study drug (UPA) can affect the timing and length of your next menstrual 
period. Other less common side effects include: 
• 
Headache (18%) 
• 
Nausea (13%) 
• 
Abdominal Pain (8-15%) 
• 
Menstrual cramping (7-13%) 
• 
Bleeding/spotting between period (9%) 
• 
Fatigue (6%) 
• 
Dizziness (5%) 
 
As with any drug, allergic reactions may occur due to the study drug. These may range from 
mild to severe, can be life-threatening/fatal and include hives, difficulty breathing, and swelling 
of your face, lips, tongue, or throat. You should seek emergency medical treatment should you 
experience an allergic reaction. 
 
If you are nursing an infant or you are pregnant now, you must not be in the study.  The study 
medication does not harm a pregnancy or a nursing infant but both of these states could 
 
Screening  
Visit 0 
 
Control Cycle 
Starting 
Cycle 1 day 
7-8 
Treatment 
Cycle 
Starting Cycle 
2 day 7-8 
Washout 
Cycle 3 
Treatment 
Cycle 
Starting Cycle 
4 day 7-8 
Consent, Screening tests 
and medical history  
X 
 
 
 
 
Phone or email contact 
 
 
 
X 
 
Blood draw 
X 
X 
X 
 
X 
Ultrasound 
 
X 
X 
 
X 
Study Medication & urine 
pregnancy test 
 
 
X* 
 
X* 
Longer series of blood 
draws (over 5 hours) 
 
 
X** 
 
X** 
Total time 
1 hour 
30min/visit 
30 min/visit 
for all but 1 
visit which will 
be 2 hours 
 
30 min/visit for 
all but 1 visit 
which will be 2 
hours 


 
 
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adversely impact the main study outcomes. If you are at risk for pregnancy, the investigator will 
discuss what types of birth control are acceptable for use during this study. You will have to use 
contraception or not be at risk for pregnancy the entire time you are in this study.  If you become 
pregnant during the research study, please tell the investigator and your doctor immediately. 
 
There are several drugs (prescription and non-prescription) that may change the drug level of 
the study medication which would interfere with the purpose of this study. The investigator will 
carefully review all of the drugs you are taking before giving you the study drug.  If any other 
health care provider prescribes any new drug(s), vitamins, or supplements for you while you are 
in this study, please tell the investigator before you take the new drug.  You could also have that 
provider talk to the investigator before prescribing the new drug.  Do not take any new over-the-
counter drugs or supplements while you are in this study unless you first check with the 
investigator. 
 
Blood Draws 
Blood samples are taken at each visit to evaluate your hormone levels and at one of the visits, 
we plan to draw a series of blood samples. Blood draws will be performed through a single stick 
venipuncture at most visits except the visit where several blood draws are needed. At that visit, 
an IV will be used to draw your blood unless you prefer venipuncture. There is a small chance 
that the needle will cause bleeding, a bruise, an infection, or fainting. It is unlikely that this 
amount of blood removal at one time or over the period of the study will result in low blood 
levels or symptoms. 
 
Transvaginal Ultrasound 
There are no known harmful effects of a vaginal probe ultrasound.  You may experience slight 
vaginal discomfort. 
 
BENEFITS: 
 
You will not benefit from being in this study.  However, by serving as a subject, you may help us 
learn how to benefit patients in the future. 
 
ALTERNATIVES:  
You may choose not to be in this study.   
 
CONFIDENTIALITY  
We will take steps to keep your personal information confidential, but we cannot guarantee total 
privacy. 
 
We will create and collect health information about you as described in the Purpose and 
Procedures sections of this form.  Health information is private and is protected under federal 
law and Oregon law.  By agreeing to be in this study, you are giving permission (also called 
authorization) for us to use and disclose your health information as described in this form. 
 
The investigators, study staff, and others at OHSU may use the information we collect and 
create about you in order to conduct and oversee this research study and store in the Women’s 
Health Research Unit repository (IRB# 6748) for possible future research. 
 
We may release this information to others outside of OHSU who are involved in conducting or 
overseeing research, including: 
 
• 
The Food and Drug Administration 
• 
The Office for Human Research Protections, a federal agency that oversees research 
involving humans 
• 
The National Center for Research Resources  
• 
Greenphire Clincard – debit card service 


 
 
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Those listed above may also be permitted to review and copy your records, including your 
medical records. 
 
We will not release information about you to others not listed above, unless required or 
permitted by law.  We will not use your name or your identity for publication or publicity 
purposes, unless we have your special permission. 
 
Blood samples or information from this study may be shared with other investigators for future 
research studies.  All identifying information about you will be removed from the samples before 
they are released to any other investigators. 
 
We may continue to use and disclose your information as described above indefinitely.  
 
Some of the information collected and created in this study may be placed in your OHSU 
medical record.  While the research is in progress, you may or may not have access to this 
information.  After the study is complete, you will be able to access any study information that 
was added to your OHSU medical record.  If you have questions about what study information 
you will be able to access, and when, ask the investigator. 
 
COMMERCIAL DEVELOPMENT:  
Samples and information about you or obtained from you in this research may be used for 
commercial purposes, such as making a discovery that could, in the future, be patented or 
licensed to a company, which could result in a possible financial benefit to that company, 
OHSU, and its researchers.  There are no plans to pay you if this happens.  You will not have 
any property rights or ownership or financial interest in or arising from products or data that may 
result from your participation in this study.  Further, you will have no responsibility or liability for 
any use that may be made of your samples or information. 
 
COSTS:   
There will be no cost to you or your insurance company to participate in this study. You will be 
compensated up to $1720 depending on the number of study visits you complete. The 
compensation amounts are as follows: 
• 
Screening visit (all participants): $20 
• 
Routine study visits without serial blood draws: $50 
• 
Study visit with serial blood draws: $100  
 
Payment received as compensation for participation in research is considered taxable income 
for a research subject.  If payments are more than $600 in any one calendar year, OHSU is 
required to report this information to the Internal Revenue Service (IRS).  Research subject 
payments exceeding $600 during any calendar year will result in a 1099 (Miscellaneous 
Income) form being issued to the research subject and a copy will be sent to the IRS.  
 
You may receive payment via a debit card or check.  If you receive payments using a debit card, 
details on how to use the card are detailed in the included card member agreement, as well as 
on a separate FAQ sheet.  There may be fees (for example, if the card is inactive for more than 
six months), explained in those documents.  Any fees will be deducted from the balance on your 
card. 
 
We may request your social security number in order to process any payments for participation. 
 
LIABILITY:   
If you believe you have been injured or harmed as a result of participating in this research and 
require treatment, contact Dr. Alison Edelman at 503-418-2585 or call 503-494-8311 and ask 
the operator to have the operator page her. 


 
 
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If you are injured or harmed by the study procedures or study drug you will be treated.  OHSU 
and the funder do not offer any financial compensation or payment for the cost of treatment if 
you are injured or harmed as a result of participating in this research.  Therefore, any medical 
treatment you need may be billed to you or your insurance.  However, you are not prevented 
from seeking to collect compensation for injury related to negligence on the part of those 
involved in the research.  Oregon law (Oregon Tort Claims Act (ORS 30.260 through 30.300)) 
may limit the dollar amount that you may recover from OHSU or its caregivers and researchers 
for a claim relating to care or research at OHSU, and the time you have to bring a claim. 
 
If you have questions on this subject, please call the OHSU Research Integrity Office at (503) 
494-7887. 
 
PARTICIPATION: 
If you have any questions, concerns, or complaints regarding this study now or in the future, 
contact Dr. Alison Edelman at 503-418-2585 or call 503-494-8311 and ask the operator to have 
the operator page her. 
 
This research is being overseen by an Institutional Review Board (“IRB”). You may talk to the 
IRB at (503) 494-7887 or irb@ohsu.edu if: 
• 
Your questions, concerns, or complaints are not being answered by the research 
team. 
• 
You want to talk to someone besides the research team. 
• 
You have questions about your rights as a research subject. 
• 
You want to get more information or provide input about this research. 
 
You may also submit a report to the OHSU Integrity Hotline online at 
https://secure.ethicspoint.com/domain/media/en/gui/18915/index.html or by calling toll-free (877) 
733-8313 (anonymous and available 24 hours a day, 7 days a week).   
 
Your participation in this study is voluntary.  You do not have to join this or any research study.  
You do not have to allow the use and disclosure of your health information in the study, but if 
you do not, you cannot be in the study 
 
If you do join the study and later change your mind, you have the right to quit at any time.  This 
includes the right to withdraw your authorization to use and disclose your health information. If 
you choose not to join any or all parts of this study, or if you withdraw early from any or all parts 
of the study, there will be no penalty or loss of benefits to which you are otherwise entitled, 
including being able to receive health care services or insurance coverage for services.  Talk to 
the investigator if you want to withdraw from the study. 
 
 
If you no longer want your health information to be used and disclosed as described in this form, 
you must send a written request or email stating that you are revoking your authorization to: 
 
Alison Edelman, MD, MPH 
3181 SW Sam Jackson, UHN 50 
Portland, OR 97239 
edelmana@ohsu.edu  
 
 
Your request will be effective as of the date we receive it.  However, health information collected 
before your request is received may continue to be used and disclosed to the extent that we 
have already acted based on your authorization.   
 


 
 
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If in the future you decide you no longer want to participate in this research, we will remove your 
name and any other identifiers from your samples and information, but the material will not be 
destroyed and we will continue to use it for research. 
 
You may be removed from the study if investigator or funder stops the study, you become 
pregnant, you develop serious side effects or cannot tolerate the study medication, if we are 
unable to consistently perform the study procedures on you (e.g. cannot obtain blood), or you 
do not follow study instructions.  
 
We will give you any new information during the course of this research study that might change 
the way you feel about being in the study. 
 
Your health care provider may be one of the investigators of this research study and, as an 
investigator, is interested in both your clinical welfare and in the conduct of this study.  Before 
entering this study or at any time during the research, you may ask for a second opinion about 
your care from another doctor who is in no way involved in this project.  You do not have to be 
in any research study offered by your physician.   
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. law. This web site will not include information that can identify you. At 
most, the web site will include a summary of the results. You can search this web site at any 
time. 
 
The participation of OHSU students or employees in OHSU research is completely voluntary 
and you are free to choose not to serve as a research subject in this protocol for any reason.  If 
you do elect to participate in this study, you may withdraw from the study at any time without 
affecting your relationship with OHSU, the investigator, the investigator’s department, or your 
grade in any course.   
 
SIGNATURES: 
 
Your signature below indicates that you have read this entire form and that you agree to be in 
this study.   
 
We will give you a copy of this signed form. 
 
 
 
Subject Printed Name 
 
Subject Signature 
 
Date 
Person Obtaining Consent Printed Name 
 
Person Obtaining Consent Signature 
 
Date 
 

Prot_SAP_002.pdf: 
Title: Effectiveness of Orally Dosed Emergency Contraception in Obese Women – UPA 
NCT number: NCT02859337 
Document Date: March 1, 2016 
 
 


PROTOCOL FOR CT.GOV 
This randomized cross-over study was conducted at Oregon Health & Science University (OHSU) in 
Portland, OR, USA and Eastern Virginia Medical School (EVMS) Norfolk, VA, USA. The Institutional 
Review Board (IRB) at OHSU and EVMS approved the study protocol. We recruited healthy women 18-
35 years old who with regular menstrual cycles (21-35 days) with a BMI at or greater than 30 kg/m2 and a 
weight of 176 lbs or more (80 kg).  In addition to this, 12 women with a BMI <25 kg/m2 were also 
recruited as controls. All subjects were required not to be at risk for pregnancy (e.g. abstinent, non-
hormonal method of birth control, or non-sperm producing partner). Major exclusion criteria obtained via 
participant report, review of medical records, and clinical exam included sensitivity or allergy to UPA; 
treatment for infertility; metabolic disorders including uncontrolled thyroid dysfunction or polycystic 
ovarian syndrome or clinical evidence of androgen excess; a screening serum progesterone level <3 
ng/mL; impaired liver or renal function; actively seeking or involved in a weight loss program (weight 
stable) or prior bariatric surgery; pregnancy or seeking pregnancy; breastfeeding; recent (8 weeks) use of 
hormonal contraception; smoking, vaping, or chronic marijuana use.   
 
After an initial telephone screening, participants completed an in-person screening visit to collect baseline 
demographic and health information and a serum progesterone level during luteal phase to confirm 
ovulatory status (progesterone level ≥3 ng/mL), an inclusion criterion for participation. All participants 
completed written informed consent prior to any study procedures. The study was conducted over three 
menstrual cycles, Cycles 1 and 3 were treatment cycles interspersed by Cycle 2, a washout cycle. For the 
normal BMI control group, participants only underwent one treatment cycle. We did not have participants 
undergo a baseline cycle with ultrasound and hormone monitoring. Participants could request to space 
Cycle 1 and 3 longer than 1 cycle for personal scheduling conflicts or study staff had participants delay an 
additional cycle, if menses delay occurred in Cycle 2 but if spacing was longer than 3 months, then 
rescreening would need to take place (n = 0).  Additionally, our study procedures overlapped with the first 


six months of the COVID-19 pandemic resulting in suspended procedures for several months as directed 
by state and institutional mandates.  
 
Our monitoring procedures were as follows: day 6-8 of treatment cycles 1 and 3, participants came in 
every other day until a dominant follicle measuring ≥15 mm in at least one dimension was visualized. 7,9,10 
These visits consisted of follicular activity monitoring via transvaginal ultrasound and blood sampling for 
progesterone (P4), estradiol (E2), and luteinizing hormone (LH). After a pregnancy test was performed 
and the results were negative, the cohort with a BMI at or greater than 30 kg/m2 and a weight of 176 lbs 
were randomized to UPA 30 mg or 60 mg for Cycle 1 and then the other dose for Cycle 3. The OHSU 
research pharmacy maintained the computer-generated randomization scheme and kept treatment 
assignments in a locked database. Those in the control group, received a single dose of UPA (30 mg) 
during Cycle 1 only. Following dosing, all subjects were seen daily for blood sampling and ultrasound 
monitoring until evidence of follicle rupture (>50% reduction of mean size or complete disappearance of 
follicle) or for up to 7 days.4,7,9,10  
 
Participants could volunteer for additional study procedures to obtain PK samples. PK parameters were 
obtained via serum samples through an indwelling catheter. We obtained samples during treatment cycles 
at the time of dosing at 0.5, 2, 1.5, 2, 3, 4, 24, 48, 72, 96, and 120 hours. PK parameters were generated 
by noncompartmental methods using WinNonLin (Pharsight, Mountain View, CA). Cmax and time to 
maximum Cmax are observed values. Area under the curve (AUC) was calculated from Time 0 to 120 hr 
(AUC0-120) using the linear trapezoidal rule and then extrapolated to infinity which provide a more 
accurate calculation of drug clearance (Rowland 1980). Drug half-life (t1/2), oral clearance (CL), and 
volume of distribution (VD) will be generated using standard pharmacokinetic calculations (t1/2 
=0.693/λz where λz is the terminal elimination rate constant; CL=dose/AUC0-infinity; VD=CL// λz). 
Descriptive statistics will be generated for each parameter [mean (standard deviation)], concentration-
time curves will be generated for all of the doses and their respective BMI groups. Depending on the 


normality of the data, parametric or nonparametric testing will be performed for each parameter between 
the normal and obese BMI EC 30 mg groups and paired statistics will be utilized to compare obese BMI 
30 versus 60 mg UPA groups. 
 
Our primary outcome was the difference in the proportion of subjects with no follicle rupture 5 days post-
dosing (yes/no) between dosing groups (30 mg vs 60 mg) in the BMI at or greater than 30 kg/m2 cohort. 
Our main secondary outcome was the timing (day) of follicle rupture between dosing groups in the BMI 
at or greater than 30 kg/m2 cohort. We also calculated these outcomes for our control group and 
descriptively compared it with the BMI at or greater than 30 kg/m2 cohort. If the date of follicle rupture 
was unclear by ultrasound imaging (e.g. collapse was seen but reduction of size was <50%), we utilized 
serum hormone levels to adjudicated day of rupture. Two investigators independently reviewed these 
cycles while being masked to dosing and if a disagreement occurred, a third investigator was engaged.  
 
Hormone assays were performed by The Endocrine Technologies Core (ETC) at the Oregon National 
Primate Research Center (ONPRC, Beaverton, Oregon (https://www.ohsu.edu/onprc/endocrine-
technologies-core) performed the hormone, UPA, and Monodemethyl-UPA assays. Serum E2, P4, and 
LH were analyzed by a Roche Cobas e411 chemiluminescence-based automated immunoassay platform 
(Roche Diagnostics, Indianapolis, IN). The sensitivities of the E2, P, and LH assays for the Roche e411 
are 5 pg/ml, 0.050 ng/ml, and 0.1 mIU/ml, respectively. The intra- and inter-assay variation with the 
Roche e411 in the ETC is consistently less than 7% for all assays. Quality control sample analyses were 
repeated prior to each assay run. Serum ulipristal acetate (UPA) and N-monodemethylated (NDM)-UPA 
concentrations were simultaneously determined by ultra-high performance liquid chromatography-heated 
electrospray ionization-tandem triple quadrupole mass spectrometry (LC-MS/MS) on a Shimadzu 
Nexera-LCMS-8050 instrument (Shimadzu Scientific, Kyoto, Japan). The lower limit of quantification 
for both UPA and NDM-UPA was 0.19 ng/ml. Samples with concentrations above 200 ng/ml were re-
analyzed after 1:5 dilution in 0 standard. Data processing and analysis were performed using 


LabSolutions Software, V5.72 (Shimadzu). Intra-assay coefficient of variation (CV) for UPA ranged from 
3.2-14.3% with an inter-assay CV of 6.3% (n=5 assays).  Intra-assay CV for NDM-UPA ranged from 2.9-
7.4% with an inter-assay CV of 4.5% (n=5 assays). Accuracy was 104.8% for UPA and 106.5% for 
NDM-UPA. The UPA and NDM-UPA assays were developed and validated largely following FDA 
guidelines for bioanalytical method validation [FDA Bioanalytical Method Validation Guidance for 
Industry, 2018] by assessing specificity, stability, precision, accuracy, extraction efficiency (recovery), 
calibration curve, sensitivity, and reproducibility.