Clinical trial NCT02940522: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Comparing Bioavailability When Makena® is Administered in Healthy Post-menopausal Women
Lead sponsor: AMAG Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2016-10-21
Enrollment: 122
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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:

1. Currently taking any estrogen/progesterone hormone replacement therapy (HRT).
2. 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
3. Poorly controlled diabetes.
4. History or current evidence of deep vein thrombosis, pulmonary embolism or arterial thromboembolic disease (e.g., stroke, myocardial infarction).
5. Known, suspected, or current history of carcinoma of the breast.
6. Subjects with a past history of breast cancer on aromatase inhibitors or selective estrogen receptor modulators.
7. Known, suspected, or current history of hormone dependent tumor within the last 5 years.
8. Any current or recent (within previous 12 months) genital bleeding of unknown etiology.
9. Receipt of any investigational drug within 30 days.
10. 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.
11. Any estrogen, progestin, or selective estrogen receptor modulator (SERM) treatment within specified time windows before the study start, ranging from 2 to 6 months.
12. High blood pressure at the screening evaluation, defined as systolic blood pressure \> 150 mm Hg or diastolic blood pressure \> 90 mm Hg.
13. History of excessive alcohol consumption (on average more than 14 units of alcohol/week) during the past 12 months.
14. Use of tobacco products within 30 days of the start of the study.

Primary outcomes:
measure: Comparison of Areas Under the Curve (AUC) to the Last Time With a Concentration ≥ LLOQ [AUC0-t] and to Infinity [AUCinf]
timeFrame: 9 weeks
measure: Comparison of the Maximum Plasma Concentration (Cmax)
timeFrame: 9 weeks
Secondary outcomes:
measure: Comparison of Tmax
timeFrame: 9 weeks
measure: Comparison of AUC (0-168)
timeFrame: 9 weeks
measure: Comparison of t1/2
timeFrame: 9 weeks
measure: Comparison of Elimination Rate Constant
timeFrame: 9 weeks
Other outcomes:
Locations:
city: Anaheim
country: United States
state: California
city: DeLand
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: San Antonio
country: United States
state: Texas
Study officials:
affiliation: AMAG Pharmaceuticals, Inc.
name: Julie Krop, MD
role: STUDY_CHAIR
References:
citation: Krop J, Kramer WG. Comparative Bioavailability of Hydroxyprogesterone Caproate Administered via Intramuscular Injection or Subcutaneous Autoinjector in Healthy Postmenopausal Women: A Randomized, Parallel Group, Open-label Study. Clin Ther. 2017 Dec;39(12):2345-2354. doi: 10.1016/j.clinthera.2017.10.020. Epub 2017 Nov 27.