Study Assessing Injection Pain of Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL) When Administered Via Subcutaneous Auto-injector vs Intramuscular Injection Via Needle and Syringe in Healthy Post-menopausal Women

• Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL) (Drug), also known as Makena SQ
• Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL) (Drug), also known as Makena

Primary outcomes

• Comparison of Average Pain Intensity [4 weeks]: Comparison of average pain intensity associated with the administration of Makena® via subcutaneous autoinjector versus intramuscular injection (averaged over 4 visits). Score on a scale: 0 (No Pain) up to 10 (Worst Pain Imaginable)

Secondary outcomes

• Clinician Assessment of Ease of Injection Technique [4 weeks]: Investigate the clinician's assessment of the ease of injection technique associated with the administration of Makena® via subcutaneous auto-injector versus intramuscular injection as measured by a categorical scale. Scores were as follows: completely dissatisfied = -3; mostly dissatisfied = -2, somewhat dissatisfied = -1, neither satisfied nor unsatisfied = 0, somewhat satisfied = 1, mostly satisfied = 2, completely satisfied = 3
• Clinician Assessment of Ease of Drug Preparation [4 weeks]: Investigate the clinician's assessment of the ease of drug preparation associated with the administration of Makena® via subcutaneous auto-injector versus intramuscular injection as measured by a categorical scale. Scores were as follows: completely dissatisfied = -3; mostly dissatisfied = -2, somewhat dissatisfied = -1, neither satisfied nor unsatisfied = 0, somewhat satisfied = 1, mostly satisfied = 2, completely satisfied = 3

Sex: Female, ages: 50 Years to 75 Years, accepts healthy volunteers

Inclusion Criteria:

1. Female subjects aged 50 to 75 years of age, inclusive, at Screening Visit.
2. Follicle stimulating hormone (FSH) levels greater than 40 mIU/mL.
3. Naturally or surgically postmenopausal with or without an intact uterus.

Exclusion Criteria:

1. Have history of or positive test results for HIV or hepatitis B or C.
2. A significant history or current evidence of chronic infectious disease, organ dysfunction especially cardiovascular, renal, or hepatic disorders or other medical condition.
3. Receiving or have received chronic opioid therapy within 12 months.
4. Unwilling to stop taking/using:

   * pain medication.
   * topical analgesic or anti-inflammatory treatment. Topical analgesics must be washed out by at least 72 hours in the areas to be treated before randomization.
5. History of alcohol abuse (regularly drinks > 4 units of alcohol per day; 8 oz. beer, 3 oz. wine, 1 oz. spirits) or prescription/illicit drug abuse in the last 12 months.
6. Currently taking any estrogen/progesterone hormone replacement therapy (HRT).
7. 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.
8. Poorly controlled diabetes (Hgb A1C >8).
9. Current or history of thrombosis or thromboembolic disorders.
10. Known or suspected breast cancer, other hormone-sensitive cancer or tumor, or history of these conditions within the last 5 years.
11. Any current or recent (within previous 12 months) vaginal bleeding.
12. Uncontrolled hypertension.
13. A chronic pain condition (i.e. chronic back pain) that may confound the assessments of injection pain.

Participant flow

Outcome results

• Comparison of Average Pain Intensity (Primary), Number, Participants with Injection Site Pain: Treatment A 3; Treatment B 2
• Clinician Assessment of Ease of Injection Technique (Secondary), Mean, units on a scale: Treatment A 2.8 +/- 0.43; Treatment B 2.3 +/- 1.32 (p 0.093)
• Clinician Assessment of Ease of Drug Preparation (Secondary), Mean, units on a scale: Treatment A 2.8 +/- 0.43; Treatment B 2.5 +/- 1.14 (p 0.234)

Adverse events

Time frame: Approximately 66 days

Serious adverse events by term

Other adverse events by term

Limitations and caveats: The Sponsor elected to discontinue the study prematurely due to business reasons. The only parameters analyzed for efficacy were Ease of Drug Preparation and Ease of Injection Technique.

• Neil Singla, MD, Principal investigator, Lotus Clinical Research, LLC