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

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

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

Study Overview

• Status: Completed
• Conditions: Comparing Bioavailability When Makena® is Administered in Healthy Post-menopausal Women
• Intervention / Treatment: Drug: Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
  • Florida
    • DeLand, Florida, United States, 32720
    • Miami, Florida, United States, 33143
    • Orlando, Florida, United States, 32809
  • Texas
    • San Antonio, Texas, United States, 78209

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment A; Subcutaneous (SQ) injection using an autoinjector	Drug: Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL); Other Names: Makena
ACTIVE_COMPARATOR: Treatment B; Intramuscular injection (IM) using syringe and needle	Drug: Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL); Other Names: Makena

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AMAG Pharmaceuticals, Inc.
• Investigators: Study Chair: Julie Krop, MD, AMAG Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2016
• Primary Completion (ACTUAL): December 1, 2016
• Study Completion (ACTUAL): March 1, 2017

Study Registration Dates

• First Submitted: October 17, 2016
• First Submitted That Met QC Criteria: October 19, 2016
• First Posted (ESTIMATE): October 21, 2016

Study Record Updates

• Last Update Posted (ACTUAL): April 28, 2022
• Last Update Submitted That Met QC Criteria: March 31, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Progestins; 17 alpha-Hydroxyprogesterone Caproate; 11-hydroxyprogesterone
• Other Study ID Numbers: AMAG-HPC-PK-010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO