Contraception
Conditions
Keywords
Emergency contraception
Brief summary
A well-designed pharmacokinetics (PK) study may identify the physiologic basis for observed differences in levonorgestrel emergency contraception (LNG-EC) and ulipristal acetate emergency contraception (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.
Detailed description
Eligible women will present to the division research office, 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 versus 30-39.9). 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.
Interventions
DRUGLNG-EC
FDA-approved emergency contraceptive pill containing levonorgestrel 1.5mg
DRUGUPA-EC
FDA-approved emergency contraceptive pill containing ulipristal acetate 30mg
Sponsors
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Women aged 18-45 years * English-speaking * BMI 18.5-24.9 kg/m2 or obese BMI 30.0-39.9 kg/m2 * 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 intrauterine system (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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time 0 to 24 Hours of Serum LNG Concentration | Up to 24 hours | LNG-EC PK parameter (AUC 0-24 h) in women with normal and obese BMI women. |
| Area Under the Curve From Time 0 to 24 Hours of Serum UPA Concentration | Up to 24 hours | UPA-EC PK parameter (AUC 0-24 h) in women with normal and obese BMI women. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clearance of Serum LNG | Up to 24 hours | (Cl) calculated in women with normal and obese BMI |
| Clearance of Serum UPA | Up to 24 hours | (Cl) calculated in women with normal and obese BMI |
| Maximum Concentration of Serum LNG | Up to 24 hours | (Cmax) calculated in women with normal and obese BMI |
| Elimination Half-life of Serum LNG | Up to 24 hours | (t1/2) calculated in women with normal and obese BMI |
| Time to Maximum Concentration of Serum LNG | Up to 24 hours | (Tmax) calculated in women with normal and obese BMI |
| Time to Maximum Concentration of Serum UPA | Up to 24 hours | (Tmax) calculated in women with normal and obese BMI |
| Maximum Concentration of Serum UPA | Up to 24 hours | (Cmax) calculated in women with normal and obese BMI |
| Elimination Half-life of Serum UPA | Up to 24 hours | (t1/2) calculated in women with normal and obese BMI |
Countries
United States
Participant flow
Pre-assignment details
No significant events in the study that occur after participant enrollment, but prior to assignment of participants to an arm or group.
Participants by arm
| Arm | Count |
|---|---|
| Normal-BMI Women with normal BMI will receive the first EC dose and complete PK assessments; then return to the clinic after at least 8 days to receive the second study drug and complete the same assessments. The study drugs (LNG-EC and UPA-EC will be given in random order). | 16 |
| Obese-BMI Women with obese BMI will receive the first EC dose and complete PK assessments; then return to the clinic after at least 8 days to receive the second study drug and complete the same assessments. The study drugs (LNG-EC and UPA-EC will be given in random order). | 16 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Normal-BMI | Obese-BMI | Total |
|---|---|---|---|
| Age, Continuous | 28.8 years | 32.3 years | 30 years |
| Region of Enrollment United States | 16 Participants | 16 Participants | 32 Participants |
| Sex: Female, Male Female | 16 Participants | 16 Participants | 32 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 4 / 8 | 3 / 8 | 4 / 8 | 2 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Area Under the Curve From Time 0 to 24 Hours of Serum LNG Concentration
LNG-EC PK parameter (AUC 0-24 h) in women with normal and obese BMI women.
Time frame: Up to 24 hours
Population: Cross-over study: 16 normal-BMI and 16 obese-BMI enrolled and each participant received both drugs in random order.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Normal-BMI | Area Under the Curve From Time 0 to 24 Hours of Serum LNG Concentration | 208.5 ng*h/mL |
| Obese-BMI | Area Under the Curve From Time 0 to 24 Hours of Serum LNG Concentration | 100.8 ng*h/mL |
p-value: <0.01t-test, 2 sided
Primary
Area Under the Curve From Time 0 to 24 Hours of Serum UPA Concentration
UPA-EC PK parameter (AUC 0-24 h) in women with normal and obese BMI women.
Time frame: Up to 24 hours
Population: Cross-over study: 16 normal-BMI and 16 obese-BMI enrolled and each participant received both drugs in random order.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Normal-BMI | Area Under the Curve From Time 0 to 24 Hours of Serum UPA Concentration | 293.5 ng*h/mL |
| Obese-BMI | Area Under the Curve From Time 0 to 24 Hours of Serum UPA Concentration | 362.5 ng*h/mL |
p-value: 0.15t-test, 2 sided
Secondary
Clearance of Serum LNG
(Cl) calculated in women with normal and obese BMI
Time frame: Up to 24 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Normal-BMI | Clearance of Serum LNG | 4.8 L/h |
| Obese-BMI | Clearance of Serum LNG | 9.8 L/h |
Secondary
Clearance of Serum UPA
(Cl) calculated in women with normal and obese BMI
Time frame: Up to 24 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Normal-BMI | Clearance of Serum UPA | 4.1 L/h |
| Obese-BMI | Clearance of Serum UPA | 3.0 L/h |
Secondary
Elimination Half-life of Serum LNG
(t1/2) calculated in women with normal and obese BMI
Time frame: Up to 24 hours
Population: Cross-over study: 16 normal-BMI and 16 obese-BMI enrolled and each participant received both drugs in random order.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Normal-BMI | Elimination Half-life of Serum LNG | 27.0 h |
| Obese-BMI | Elimination Half-life of Serum LNG | 50.4 h |
Secondary
Elimination Half-life of Serum UPA
(t1/2) calculated in women with normal and obese BMI
Time frame: Up to 24 hours
Population: Cross-over study: 16 normal-BMI and 16 obese-BMI enrolled and each participant received both drugs in random order.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Normal-BMI | Elimination Half-life of Serum UPA | 34.9 h |
| Obese-BMI | Elimination Half-life of Serum UPA | 65.9 h |
Secondary
Maximum Concentration of Serum LNG
(Cmax) calculated in women with normal and obese BMI
Time frame: Up to 24 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Normal-BMI | Maximum Concentration of Serum LNG | 18.2 ng/mL |
| Obese-BMI | Maximum Concentration of Serum LNG | 10.8 ng/mL |
Secondary
Maximum Concentration of Serum UPA
(Cmax) calculated in women with normal and obese BMI
Time frame: Up to 24 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Normal-BMI | Maximum Concentration of Serum UPA | 89.3 ng/mL |
| Obese-BMI | Maximum Concentration of Serum UPA | 95.6 ng/mL |
Secondary
Time to Maximum Concentration of Serum LNG
(Tmax) calculated in women with normal and obese BMI
Time frame: Up to 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal-BMI | Time to Maximum Concentration of Serum LNG | 2.0 h | Standard Deviation 2 |
| Obese-BMI | Time to Maximum Concentration of Serum LNG | 3.0 h | Standard Deviation 1 |
Secondary
Time to Maximum Concentration of Serum UPA
(Tmax) calculated in women with normal and obese BMI
Time frame: Up to 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal-BMI | Time to Maximum Concentration of Serum UPA | 1.6 h | Standard Deviation 1 |
| Obese-BMI | Time to Maximum Concentration of Serum UPA | 1.5 h | Standard Deviation 1 |