17-OHPC in Pregnancy: IM vs SC Routes

Study Overview
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Brief Summary
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This study will compare the plasma concentration x time curve or Area Under the Curve (AUC) and the side effects reported with 250 mg intramuscular (IM) and 275 mg subcutaneous (SC) injections of 17-hydroxyprogesterone caproate (17-OHPC).

Detailed Description
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17-hydroxyprogesterone caproate (17-OHPC) is used in women with a prior preterm birth (PTB) as it reduces recurrences by a third. The drug is administered intramuscularly (IM) but that creates discomfort and in many instances requires repeated office visits as the drug is administered weekly from 16-20 weeks until 36 weeks or delivery. AMAG Pharmaceuticals obtained FDA approval to administer the drug subcutaneously (SC) based on demonstration of bioequivalence of a dose of 275 mg SC to a dose of 250 mg IM. That bioequivalence study was performed in postmenopausal women who received a single dose. This study will be performed in pregnant women with repeated injections both to demonstrate that equivalent exposure is seen and to assess the side effects and acceptance of each route of administration. A pharmacokinetic (PK) study will be performed after participants have reached steady state (after 9 injections). Participants will receive their injections from research personnel up until the time of completion of the PK study. Home injections will be an option for all participants after the PK study is completed.

Official Title
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A Comparison of Intramuscular and Subcutaneous Administration of 17-hydroxyprogesterone Caproate (17-OHPC) in Pregnancy

Conditions
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Preterm Birth

Intervention / Treatment
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* Drug: 17-Hydroxyprogesterone Caproate 250 mg IM Dose
* Drug: 17-Hydroxyprogesterone Caproate 275 mg SC Dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant female with documented prior birth between 16 0/7- 36 6/7 week gestation from spontaneous preterm labor or preterm premature rupture of membranes Gestational age (GA) < 22 weeks, based on study determined GA (as treatment must start between 16 0/7 and 21 6/7 weeks) Singleton gestation Age between 18 - 45 years Able to give informed consent and undergo all study procedures including a single seven day pharmacokinetic study which requires daily venipunctures and willingness to answer questions about side effects and discomfort at each study visit. Exclusion Criteria: Known major fetal anomaly or chromosomal anomalies that might affect gestational age at delivery Malformation of uterus (uterine didelphus, septate uterus or bicornuate uterus) Medical or obstetrical complication that might affect gestational age at delivery, such as active ulcerative colitis, liver tumors, liver disease/failure, renal disease/failure, undiagnosed vaginal bleeding unrelated to pregnancy, or hypertension requiring 2 or more agents Current or history of thrombosis or thromboembolic disorders Known or suspected breast cancer, other hormone-sensitive cancer, or a history of these conditions Moderately severe depression (Patient Health Questionnaire-9 (PHQ-9) score ≥15, Edinburgh Postnatal Depression Scale (EPDS) score of >13, or suicidal ideation)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 17-Hydroxyprogesterone Caproate 250 mg IM Group<br>This will be an open label study and participants will not be randomized to a treatment group. The women will be prescribed 17-OHPC by their physicians because of their obstetric history. The investigators will approach pregnant women who are going to be treated with 17-OHPC and ask them to participate. The participants will select the route of administration they prefer, IM or SC. 36 participants will receive the weekly 250 mg IM dose from 16-20 weeks of pregnancy until 36 weeks or delivery. | Drug: 17-Hydroxyprogesterone Caproate 250 mg IM Dose<br>* 17-Hydroxyprogesterone Caproate is a progestin indicated to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth.<br>* Other names: 17-OHPC;|
| 17-Hydroxyprogesterone Caproate 275 mg SC Group<br>This will be an open label study and participants will not be randomized to a treatment group. The women will be prescribed 17-OHPC by their physicians because of their obstetric history. The investigators will approach pregnant women who are going to be treated with 17-OHPC and ask them to participate. The participants will select the route of administration they prefer, IM or SC. 36 participants will receive the weekly 275 mg IM dose from 16-20 weeks of pregnancy until 36 weeks or delivery. | Drug: 17-Hydroxyprogesterone Caproate 275 mg SC Dose<br>* 17-Hydroxyprogesterone Caproate is a progestin indicated to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth<br>* Other names: 17-OHPC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the plasma concentration x time curve or the Area Under the Curve (AUC) of the 275 mg subcutaneous dose of 17-OHPC to the 250 mg intramuscular dose of 17-OHPC | Evaluate the difference between the plasma concentration x time curve or the Area Under the Curve (AUC) at steady state between the 250 mg dose of 17-OHPC administered intramuscularly and the 275 mg dose of 17-OHPC administered subcutaneously with an autoinjector. | 9 weeks after initiation (26-30 weeks gestation) | 
| Compare the severity of injection related side effects of the intramuscular and subcutaneous routes of administration of 17-OHPC | Participants will complete a Visual Analog Scale (VAS) with each injection that grades the severity of injection related side effects as none, mild, moderate or severe. This data will be used to compare the side effects of the intramuscular injections to the subcutaneous injections. | from study initiation until 36 weeks of pregnancy or delivery | 
| Compare the level of injection related discomfort of the intramuscular and subcutaneous routes of administration of 17-OHPC | Participants will complete a Visual Analog Scale (VAS) with each injection that grades the level of discomfort associated with the injection as none, mild, moderate or severe. This data will be used to compare the level of discomfort of the intramuscular injections to the subcutaneous injections. | from study initiation until 36 weeks of pregnancy or delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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17-hydroxyprogesterone caproate