Comparing Bioavailability When Preservative-free Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL) is Administered as an Intramuscular Manual Injection or as a Subcutaneous Injection Using an Auto-injector in Healthy Post-menopausal Women

Study Overview
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Brief Summary
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To demonstrate that a single dose of Makena® delivered SQ via auto-injector has comparable bioavailability to a single IM injection of Makena®.

Official Title
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A Multi-Center, Randomized, Open-Label Study Comparing Bioavailability When Preservative-free Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL) is Administered as an Intramuscular Manual Injection or as a Subcutaneous Injection Using an Auto-injector in Healthy Post-menopausal Women

Conditions
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Comparing Bioavailability When Makena® is Administered in Healthy Post-menopausal Women

Intervention / Treatment
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* Drug: Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
* Drug: Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Naturally or surgically postmenopausal women, with or without an intact uterus, aged 50 to 75 years of age, inclusive. FSH levels greater than 40 mIU/mL Exclusion Criteria: Currently taking any estrogen/progesterone hormone replacement therapy (HRT). History of allergy or sensitivity to hydroxyprogesterone caproate, castor oil or any of the constituents of the study medications, or history of any drug hypersensitivity or intolerance Poorly controlled diabetes. History or current evidence of deep vein thrombosis, pulmonary embolism or arterial thromboembolic disease (e.g., stroke, myocardial infarction). Known, suspected, or current history of carcinoma of the breast. Subjects with a past history of breast cancer on aromatase inhibitors or selective estrogen receptor modulators. Known, suspected, or current history of hormone dependent tumor within the last 5 years. Any current or recent (within previous 12 months) genital bleeding of unknown etiology. Receipt of any investigational drug within 30 days. Receipt of any prescription or OTC medications that are known to alter CYP3A4 or CYP3A5 levels (e.g., carbamazepine, St. John's Wort, ketoconazole, rifampin, ritonavir, alprazolam, azithromycin, loratadine, etc.) within 14. Any estrogen, progestin, or selective estrogen receptor modulator (SERM) treatment within specified time windows before the study start, ranging from 2 to 6 months. High blood pressure at the screening evaluation, defined as systolic blood pressure > 150 mm Hg or diastolic blood pressure > 90 mm Hg. History of excessive alcohol consumption (on average more than 14 units of alcohol/week) during the past 12 months. Use of tobacco products within 30 days of the start of the study.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br>Subcutaneous (SQ) injection using an autoinjector | Drug: Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)<br> <br> * Other names: Makena SQ;|
| Active Comparator: Treatment B<br>Intramuscular injection (IM) using syringe and needle | Drug: Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)<br> <br> * Other names: Makena;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Areas Under the Curve (AUC) to the Last Time With a Concentration ≥ LLOQ [AUC0-t] and to Infinity [AUCinf] | Comparison of areas under the curve (AUC) to the last time with a concentration ≥ LLOQ [AUC0-t] and to infinity [AUCinf] for the Primary PK Population | 9 weeks | 
| Comparison of the Maximum Plasma Concentration (Cmax) | Comparison of the maximum plasma concentration (Cmax) for the Primary PK Population | 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Tmax | Comparison of PK parameter Tmax for the Primary PK population | 9 weeks | 
| Comparison of AUC (0-168) | Comparison of PK Parameter AUC (0-168) for the Primary PK Population | 9 weeks | 
| Comparison of t1/2 | Comparison of PK parameter t1/2 for the Primary PK Population | 9 weeks | 
| Comparison of Elimination Rate Constant | Comparison of the elimination rate constant for the Primary PK Population | 9 weeks |