Comparing Bioavailability When Makena® is Administered in Healthy Post-menopausal WomenPhase 1NCT02940522

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 Phase 1 study testing Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL) in people with Comparing Bioavailability When Makena® is Administered in Healthy Post-menopausal Women, run by AMAG Pharmaceuticals, Inc. at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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

Who is it for?: Ages 50 to 75 years, women onlyHealthy volunteers can take part
Conditions the study is for: Comparing Bioavailability When Makena® is Administered in Healthy Post-menopausal Women
What is being tested?: Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 122 participants
Where: 5 sitesUnited States
Study dates: Sep 2016to Mar 2017
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 50 to 75 years
Women only
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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

Who cannot join

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.

Show all 14Show fewer

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.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

Study site
Anaheim, California, 92801
Study site
DeLand, Florida, 32720
Study site
Miami, Florida, 33143
Study site
Orlando, Florida, 32809
Study site
San Antonio, Texas, 78209

Other trials in United States

About this study

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

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

Conditions: Comparing Bioavailability When Makena® is Administered in Healthy Post-menopausal Women
Being tested: Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)Drug
Also called Makena SQ
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)Drug
Also called Makena

Study groups in NCT02940522
Study group	Role	What they receive
Treatment A	Experimental	Subcutaneous (SQ) injection using an autoinjector Receives: Drug: Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
Treatment B	Active comparator	Intramuscular injection (IM) using syringe and needle Receives: Drug: Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 9 weeks
Comparison of the Maximum Plasma Concentration (Cmax)
Comparison of the maximum plasma concentration (Cmax) for the Primary PK Population
Measured: 9 weeks

Secondary outcomes (4)

Comparison of Tmax
Comparison of PK parameter Tmax for the Primary PK population
Measured: 9 weeks
Comparison of AUC (0-168)
Comparison of PK Parameter AUC (0-168) for the Primary PK Population
Measured: 9 weeks
Comparison of t1/2
Comparison of PK parameter t1/2 for the Primary PK Population
Measured: 9 weeks
Comparison of Elimination Rate Constant
Comparison of the elimination rate constant for the Primary PK Population
Measured: 9 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2016Mar 2017

First posted21 Oct 2016 (estimated)
Study startSep 2016
Primary completionDec 2016
Study completionMar 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Comparing Bioavailability When Makena® is Administered in Healthy Post-menopausal WomenStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 122 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02940522
Sponsor's protocol ID: AMAG-HPC-PK-010
Status last verified: Mar 2022
First submitted: 17 Oct 2016
Last updated: 28 Apr 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

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.
PubMed 29191450

Study at a glance

From the registry record, last updated by the sponsor on 28 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02940522
Acronym / sponsor ID: AMAG-HPC-PK-010
Conditions: Comparing Bioavailability When Makena® is Administered in Healthy Post-menopausal Women
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 122 participants (actual)
Lead sponsor: AMAG Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
Study start: Sep 2016 (actual)
Primary completion: Dec 2016 (actual)
Study completion: Mar 2017 (actual)
First posted: 21 Oct 2016 (estimated)
Results: Posted 30 Nov 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Treatment A	Experimental	Drug: Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)Subcutaneous (SQ) injection using an autoinjector
Treatment B	Active comparator	Drug: Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)Intramuscular injection (IM) using syringe and needle

Who may qualify

Ages: 50 to 75 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

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

Key exclusion criteria (14 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)Also: Makena SQ	Drug	Treatment A
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)Also: Makena	Drug	Treatment B

Primary outcome

Comparison of Areas Under the Curve (AUC) to the Last Time With a Concentration ≥ LLOQ [AUC0-t] and to Infinity [AUCinf]
Time frame: 9 weeks
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
Comparison of the Maximum Plasma Concentration (Cmax)
Time frame: 9 weeks
Comparison of the maximum plasma concentration (Cmax) for the Primary PK Population

4 secondary outcomes

Comparison of Tmax
Time frame: 9 weeks
Comparison of AUC (0-168)
Time frame: 9 weeks
Comparison of t1/2
Time frame: 9 weeks
Comparison of Elimination Rate Constant
Time frame: 9 weeks

Results and safety

Results posted to the registry on 30 Nov 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment A	59	57
Treatment B	61	59

Primary outcome: Comparison of Areas Under the Curve (AUC) to the Last Time With a Concentration ≥ LLOQ [AUC0-t] and to Infinity [AUCinf]

Time frame: 9 weeks. Geometric mean (Geometric Coefficient of Variation). Unit: hr x ng/mL

Measure	Treatment A n = 45	Treatment B n = 45
AUC(0-t)	2,313 (23.5)	2,098 (27.7)
AUC(inf)	2,469 (22.8)	2,175 (27.8)

Population analysed: The Primary PK Population consisted of 45 subjects each for both treatments for whom whole blood was analyzed. Subjects were excluded from Treatment A and Treatment B due to insufficient number of samples for planned analyses.

Primary outcome: Comparison of the Maximum Plasma Concentration (Cmax)

Time frame: 9 weeks. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	Treatment A n = 45	Treatment B n = 45
Value	7.88 (71.9)	6.91 (62.9)

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: 9 weeks.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment A	0 of 59 (0%)	32 of 59 (54.2%)	Not reported
Treatment B	0 of 61 (0%)	23 of 61 (37.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 29191450Krop 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.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Julie Krop, MD study chair

AMAG Pharmaceuticals, Inc.

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Comparison of Areas Under the Curve (AUC) to the Last Time With a Concentration ≥ LLOQ [AUC0-t] and to Infinity [AUCinf] (time frame: 9 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02940522, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2022.