17-OHPC in Pregnancy: IM vs SC Routes

Terminated

• Conditions: Preterm Birth
• Interventions: Drug: 17-Hydroxyprogesterone Caproate 250 mg IM Dose; Drug: 17-Hydroxyprogesterone Caproate 275 mg SC Dose

• Registration Number: NCT04183452
• Lead Sponsor: Steve N. Caritis, MD

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2019-11-19
• Study First Submitted QC: 2019-11-27
• Study First Posted: 2019-12-03
• Study Start: 2020-06-16
• Primary Completion: 2023-04-06
• Study Completion: 2023-04-06
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-01
• Last Update Posted: 2023-08-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 24

Inclusion Criteria

1. 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
2. Gestational age (GA) < 22 weeks, based on study determined GA (as treatment must start between 16 0/7 and 21 6/7 weeks)
3. Singleton gestation
4. Age between 18 - 45 years
5. 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

1. Known major fetal anomaly or chromosomal anomalies that might affect gestational age at delivery
2. Malformation of uterus (uterine didelphus, septate uterus or bicornuate uterus)
3. 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
4. Current or history of thrombosis or thromboembolic disorders
5. Known or suspected breast cancer, other hormone-sensitive cancer, or a history of these conditions
6. Moderately severe depression (Patient Health Questionnaire-9 (PHQ-9) score ≥15, Edinburgh Postnatal Depression Scale (EPDS) score of >13, or suicidal ideation)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
17-Hydroxyprogesterone Caproate 250 mg IM Group	17-Hydroxyprogesterone Caproate 250 mg IM Dose	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.
17-Hydroxyprogesterone Caproate 275 mg SC Group	17-Hydroxyprogesterone Caproate 275 mg SC Dose	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.

Primary Outcome Measures

Name	Time	Method
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	9 weeks after initiation (26-30 weeks gestation)	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.
Compare the severity of injection related side effects of the intramuscular and subcutaneous routes of administration of 17-OHPC	from study initiation until 36 weeks of pregnancy or delivery	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.
Compare the level of injection related discomfort of the intramuscular and subcutaneous routes of administration of 17-OHPC	from study initiation until 36 weeks of pregnancy or delivery	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.

Trial Locations

Locations (4)

University of Pittsburgh-Magee Womens Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

Christiana Care; 🇺🇸 Newark, Delaware, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Wake Forest Baptist Medical Center; 🇺🇸 Winston-Salem, North Carolina, United States