Clinical trial NCT04183452: 17-OHPC in Pregnancy: IM vs SC Routes
Official title: A Comparison of Intramuscular and Subcutaneous Administration of 17-hydroxyprogesterone Caproate (17-OHPC) in Pregnancy
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Preterm Birth
Keywords: 17-hydroxyprogesterone caproate
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: AMAG Pharmaceuticals, Inc.
First posted: 2019-12-03
Enrollment: 24
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This will be an open label study and participants will not be randomized to a treatment group. The rational for this approach is based on the expectation that the primary outcomes (AUC and side effects) will not be affected by provider or patient knowledge of or choice of treatment.

We will approach pregnant women who are going to be treated with 17-OHPC as part of their standard of care and ask them to participate. Participants will select the route of administration they prefer, intramuscular or subcutaneous.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: 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
timeFrame: 9 weeks after initiation (26-30 weeks gestation)
measure: Compare the severity of injection related side effects of the intramuscular and subcutaneous routes of administration of 17-OHPC
timeFrame: from study initiation until 36 weeks of pregnancy or delivery
measure: Compare the level of injection related discomfort of the intramuscular and subcutaneous routes of administration of 17-OHPC
timeFrame: from study initiation until 36 weeks of pregnancy or delivery
Secondary outcomes:
Other outcomes:
Locations:
city: Newark
country: United States
facility: Christiana Care
state: Delaware
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Pittsburgh
country: United States
facility: University of Pittsburgh-Magee Womens Hospital
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh-Magee Womens Hospital
name: Steve N Caritis, MD
role: PRINCIPAL_INVESTIGATOR
References: