EC PK in Women With Normal and Obese BMI
| Status: | Enrolling by invitation |
|---|---|
| Conditions: | Contraception, Contraception |
| Therapuetic Areas: | Reproductive |
| Healthy: | No |
| Age Range: | 18 - 45 |
| Updated: | 4/21/2016 |
| Start Date: | July 2015 |
| End Date: | June 2016 |
Pharmacokinetics of Levonorgestrel and Ulipristal Acetate Emergency Contraception in Women With Normal and Obese Body Mass Index
The rate of unintended pregnancy in the U.S. has remained relatively stable despite approval
of an over-the-counter levonorgestrel (LNG)-based emergency contraceptive (EC) pill,
development of a novel EC pill (ulipristal acetate (UPA)) and increased uptake of EC during
this period. Few studies have addressed risk factors for EC failure yet such an
investigation is warranted to better understand if EC can be used more successfully.
Reanalysis of data from previously conducted trials has shown that LNG-EC and UPA-EC failure
is higher in obese women than in women with normal BMI. No studies describe why these
differences exist. Pharmacokinetic (PK) and pharmacodynamic (PD) studies in obese women
using LNG-based oral contraceptive pills inform the question, however these results are
mixed. All report differences in PK parameters across BMI groups. Whether these differences
result in PD variations that could decrease OCP effectiveness is not clear.
A well-designed PK study may identify the physiologic basis for observed differences in LNG-
and UPA-EC failure rates in women with normal and obese BMI. The investigators propose a
study to compare serum LNG and UPA levels after administration of a single-dose of LNG-EC or
UPA-EC. The investigators hypothesize that there will be no difference in PK parameters
between women with normal BMI and obese women.
of an over-the-counter levonorgestrel (LNG)-based emergency contraceptive (EC) pill,
development of a novel EC pill (ulipristal acetate (UPA)) and increased uptake of EC during
this period. Few studies have addressed risk factors for EC failure yet such an
investigation is warranted to better understand if EC can be used more successfully.
Reanalysis of data from previously conducted trials has shown that LNG-EC and UPA-EC failure
is higher in obese women than in women with normal BMI. No studies describe why these
differences exist. Pharmacokinetic (PK) and pharmacodynamic (PD) studies in obese women
using LNG-based oral contraceptive pills inform the question, however these results are
mixed. All report differences in PK parameters across BMI groups. Whether these differences
result in PD variations that could decrease OCP effectiveness is not clear.
A well-designed PK study may identify the physiologic basis for observed differences in LNG-
and UPA-EC failure rates in women with normal and obese BMI. The investigators propose a
study to compare serum LNG and UPA levels after administration of a single-dose of LNG-EC or
UPA-EC. The investigators hypothesize that there will be no difference in PK parameters
between women with normal BMI and obese women.
If the research coordinator determines that the woman is ineligible for the study following
the telephone screen, the coordinator will destroy all documentation of the woman's
telephone screen. If the research coordinator determines that the woman is eligible for the
study, she will assign her to a BMI group based on the woman's reported height and weight,
reconfirm interest in study participation and obtain verbal consent for study participation.
Eligible women will present to the Division research office for Visit 1. At this time, the
study purpose and procedures will be re-explained. If the woman agrees to the terms of the
study, then she will sign a written consent for participation (see Consent). The research
coordinator will conduct an enrollment visit at which time a history and physical exam will
be completed. Each participant's BMI will be confirmed and she will be assigned to one of
two BMI groups (18.5-24.9 v. 30-39.9). Information collected during the enrollment visit
will supersede information collected during the telephone screen. At the conclusion of the
enrollment visit, the research coordinator will randomize each woman to receive a
single-dose pill of either levonorgestrel 1.5mg (like Plan B One-Step® or its generic
formulations) or ulipristal acetate 30mg (ellaOne®) on two separate occasions. The research
coordinator will work with the participant to schedule inpatient admission to the CRC for
Study Arm 1. The schedule of visits will then proceed as follows:
Visit 2 (t0-t24hour)
- Step 1 - Study participants will be admitted to the CRC where they will receive one of
the study drugs. Admission orders for each participant will be written by the PI in
advance of each patient's admission.
- Step 2 - Study participants will be given a 400 calorie meal containing 20% fat.
Standardization of meals consumed prior to drug intake will minimize variations in
gastric emptying and bioavailability of the study drugs.
- Step 3 (t0) - Thirty minutes after completing their meal, the participant will undergo
the first of thirteen 6ml blood specimen collections. CRC staff will then place an
intravenous (IV) catheter in the participant's upper extremity to facilitate blood
collections. CRC staff will collect a 6mL blood specimen for quantification of SHBG,
LNG and ulipristal acetate. S/he will then administer the study drug, which the
participant will take with a small cup of water. This will mark t0.
- Step 4 - Step 15 (t0.5, t1.0, t1.5, t2, t3, t4, t6, t8, t10, t12, t16hour) - The CRC
staff will collect 6mL blood specimens at the times listed. A research assistant will
accompany the participant from time t0-t6 in order to assist CRC staff with timing of
blood draws and handling of blood specimens. Study participants will be allowed to eat
and drink meals of their choice any time after t1.
- Step 16 (t24hour) - The CRC staff will collect the final inpatient 6mL blood specimen.
S/he will remove the study participant's IV catheter and give clear verbal and written
instructions to return to the Division of Family Planning research office in 24 hours
(t48) for collection of the last 6mL blood sample.
Visit 3 (t48hour)
- Step 1 (t48hour) - Participants will present to the Division of Family Planning
research office at New York Presbyterian Hospital for collection of one 6mL blood
specimen.
- Step 2 - The research coordinator will administer a survey to assess subjects'
satisfaction with study participation and reconfirm their desire to participate in
Study Arm2. No more than 60 days may elapse between initiation of Study Arm 1 and
initiation of Study Arm 2.
The schedule of visits for Study Arm 2 will proceed as follows:
Visit 4 (or any time between 15-60 days from Day 1)
- Step 1 - Study participants will return to the CRC approximately one month, but no
sooner than two weeks, from Day 1 of participation in Study Arm 1. Admission orders for
each participant will be written by the PI in advance of each participant's admission.
- Step 2 - Study participants will be given a 400 calorie meal containing 20% fat.
Standardization of meals consumed prior to drug intake will minimize variations in
gastric emptying and bioavailability of the study drugs.
- Step 3 (t0) - Thirty minutes after completing their meal, the participant will undergo
the first of thirteen 6ml blood specimen collections. CRC staff will then place an
intravenous (IV) catheter in the participant's upper extremity to facilitate blood
collections. CRC staff will collect a 6mL blood specimen for quantification of SHBG,
LNG and ulipristal acetate. S/he will then administer the study drug, which the
participant will take with a small cup of water. This will mark t0.
- Step 4 - Step 15 (t0.5, t1.0, t1.5, t2, t3, t4, t6, t8, t10, t12, t16hour) - The CRC
staff will collect 6mL blood specimens at the times listed. A research assistant will
accompany the participant from time t0-t6 in order to assist CRC staff with timing of
blood draws and handling of blood specimens. Study participants will be allowed to eat
and drink meals of their choice any time after t1.
- Step 16 (t24hour) - The CRC staff will collect the final inpatient 6mL blood specimen.
S/he will remove the study participant's IV catheter and give clear verbal and written
instructions to return to the Division of Family Planning research office in 24 hours
(t48) for collection of the last 6mL blood sample.
Visit 5 (i.e. or any time between 17-62 days from Day 1)
- Step 1 (t48hour) - Participants will present to the Division of Family Planning
research office at New York Presbyterian Hospital for collection of one 6mL blood
specimen.
- Step 2 - The research coordinator will administer a survey to assess subjects'
satisfaction with study participation as well as their interest in participation in
future studies.
All blood samples will be allowed to clot at room temperature for 60 minutes, separated by
centrifugation (3000 r∙min-1, 4°C, 10 min), and stored in 1 mL aliquots. The research
coordinator will assist CRC staff with preparation of t0-t6 blood specimens.
the telephone screen, the coordinator will destroy all documentation of the woman's
telephone screen. If the research coordinator determines that the woman is eligible for the
study, she will assign her to a BMI group based on the woman's reported height and weight,
reconfirm interest in study participation and obtain verbal consent for study participation.
Eligible women will present to the Division research office for Visit 1. At this time, the
study purpose and procedures will be re-explained. If the woman agrees to the terms of the
study, then she will sign a written consent for participation (see Consent). The research
coordinator will conduct an enrollment visit at which time a history and physical exam will
be completed. Each participant's BMI will be confirmed and she will be assigned to one of
two BMI groups (18.5-24.9 v. 30-39.9). Information collected during the enrollment visit
will supersede information collected during the telephone screen. At the conclusion of the
enrollment visit, the research coordinator will randomize each woman to receive a
single-dose pill of either levonorgestrel 1.5mg (like Plan B One-Step® or its generic
formulations) or ulipristal acetate 30mg (ellaOne®) on two separate occasions. The research
coordinator will work with the participant to schedule inpatient admission to the CRC for
Study Arm 1. The schedule of visits will then proceed as follows:
Visit 2 (t0-t24hour)
- Step 1 - Study participants will be admitted to the CRC where they will receive one of
the study drugs. Admission orders for each participant will be written by the PI in
advance of each patient's admission.
- Step 2 - Study participants will be given a 400 calorie meal containing 20% fat.
Standardization of meals consumed prior to drug intake will minimize variations in
gastric emptying and bioavailability of the study drugs.
- Step 3 (t0) - Thirty minutes after completing their meal, the participant will undergo
the first of thirteen 6ml blood specimen collections. CRC staff will then place an
intravenous (IV) catheter in the participant's upper extremity to facilitate blood
collections. CRC staff will collect a 6mL blood specimen for quantification of SHBG,
LNG and ulipristal acetate. S/he will then administer the study drug, which the
participant will take with a small cup of water. This will mark t0.
- Step 4 - Step 15 (t0.5, t1.0, t1.5, t2, t3, t4, t6, t8, t10, t12, t16hour) - The CRC
staff will collect 6mL blood specimens at the times listed. A research assistant will
accompany the participant from time t0-t6 in order to assist CRC staff with timing of
blood draws and handling of blood specimens. Study participants will be allowed to eat
and drink meals of their choice any time after t1.
- Step 16 (t24hour) - The CRC staff will collect the final inpatient 6mL blood specimen.
S/he will remove the study participant's IV catheter and give clear verbal and written
instructions to return to the Division of Family Planning research office in 24 hours
(t48) for collection of the last 6mL blood sample.
Visit 3 (t48hour)
- Step 1 (t48hour) - Participants will present to the Division of Family Planning
research office at New York Presbyterian Hospital for collection of one 6mL blood
specimen.
- Step 2 - The research coordinator will administer a survey to assess subjects'
satisfaction with study participation and reconfirm their desire to participate in
Study Arm2. No more than 60 days may elapse between initiation of Study Arm 1 and
initiation of Study Arm 2.
The schedule of visits for Study Arm 2 will proceed as follows:
Visit 4 (or any time between 15-60 days from Day 1)
- Step 1 - Study participants will return to the CRC approximately one month, but no
sooner than two weeks, from Day 1 of participation in Study Arm 1. Admission orders for
each participant will be written by the PI in advance of each participant's admission.
- Step 2 - Study participants will be given a 400 calorie meal containing 20% fat.
Standardization of meals consumed prior to drug intake will minimize variations in
gastric emptying and bioavailability of the study drugs.
- Step 3 (t0) - Thirty minutes after completing their meal, the participant will undergo
the first of thirteen 6ml blood specimen collections. CRC staff will then place an
intravenous (IV) catheter in the participant's upper extremity to facilitate blood
collections. CRC staff will collect a 6mL blood specimen for quantification of SHBG,
LNG and ulipristal acetate. S/he will then administer the study drug, which the
participant will take with a small cup of water. This will mark t0.
- Step 4 - Step 15 (t0.5, t1.0, t1.5, t2, t3, t4, t6, t8, t10, t12, t16hour) - The CRC
staff will collect 6mL blood specimens at the times listed. A research assistant will
accompany the participant from time t0-t6 in order to assist CRC staff with timing of
blood draws and handling of blood specimens. Study participants will be allowed to eat
and drink meals of their choice any time after t1.
- Step 16 (t24hour) - The CRC staff will collect the final inpatient 6mL blood specimen.
S/he will remove the study participant's IV catheter and give clear verbal and written
instructions to return to the Division of Family Planning research office in 24 hours
(t48) for collection of the last 6mL blood sample.
Visit 5 (i.e. or any time between 17-62 days from Day 1)
- Step 1 (t48hour) - Participants will present to the Division of Family Planning
research office at New York Presbyterian Hospital for collection of one 6mL blood
specimen.
- Step 2 - The research coordinator will administer a survey to assess subjects'
satisfaction with study participation as well as their interest in participation in
future studies.
All blood samples will be allowed to clot at room temperature for 60 minutes, separated by
centrifugation (3000 r∙min-1, 4°C, 10 min), and stored in 1 mL aliquots. The research
coordinator will assist CRC staff with preparation of t0-t6 blood specimens.
Inclusion Criteria:
- Women aged 18-45 years
- English-speaking
- BMI 18.5-24.9 or BMI 30.0-39.9
- Regular menstrual cycles
- No use of medroxyprogesterone acetate at least 6 months prior to study enrollment,
unless resumption of two menstrual cycles
- No use of levonorgestrel-IUS, etonogestrel implant or combined hormonal contraception
at least one month prior to the study and resumption of one menstrual cycle
- Women who are postpartum or post-abortion will be included if they have had at least
one menstrual cycle since their last pregnancy
Exclusion Criteria:
- Prior allergic reaction to LNG-EC or UPA-EC
- Use of hormonal emergency contraception within the past month
- Women who are currently pregnant or who are currently breastfeeding
- History of cancer other than non-melanoma skin cancer
- Medical or surgical conditions or conditions requiring therapies known to impact sex
steroid production or metabolism
- Use of HAART therapy for management of HIV infection
- Concomitant use of CYP3A4 inducers like rifampin, barbiturates, carbamazepine,
lamotrigine, bosentan, felbamate, griseofulvin, oxcarbazepine, phenytoin, St.
John's Wort and topiramate
- Current participation in any other trial of an investigational medicine or device in
the three months leading up to this study
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