Clinical Trials

Date: 2017-02-02

Type of information: Results

phase: 3

Announcement: results

Company: Amag Pharmaceuticals (USA - MA)

Product: Makena® (hydroxyprogesterone caproate injection) subcutaneous auto-injector program (Makena SQ)

Action mechanism: hormone. Makena® is a progestin indicated to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth. The effectiveness of Makena is based on improvement in the proportion of women who delivered <37 weeks of gestation. There are no controlled trials demonstrating a direct clinical benefit, such as improvement in neonatal mortality and morbidity.

Disease:

Therapeutic area: Women health

Country: USA

Trial details:

• The definitive pharmacokinetic study for the Makena SQ program is a randomized open label parallel study designed to demonstrate comparable bioavailability between subcutaneous and intramuscular injections of Makena. The study is expected to enroll 120 healthy post-menopausal women with a 1:1 randomization. (NCT02940522)
• The comparative pain study is also a randomized open label parallel study designed to compare the average injection pain of four weekly injections between the subcutaneous and intramuscular injections of Makena using a validated pain scale. The study is expected to enroll 60 healthy, post-menopausal women with a 1:1 randomization. (NCT02937766)

Latest news:

• • On February 2, 2017, Amag Pharmaceuticals announced results from its definitive pharmacokinetic study designed to demonstrate comparable bioavailability of the subcutaneous auto-injector product and the current intramuscular injection form of Makena® in approximately 120 healthy post-menopausal women.
• Makena® administered subcutaneously demonstrated bioequivalence to the intramuscular injection on area under the curve (AUC_0-to-inf 2,386 ng/mL compared to 2,086 ng/mL), with the 90 percent confidence interval for the ratio of AUC (105.17 to 124.39) falling within the 80 to 125 percent range, which the FDA uses to define bioequivalence. The mean maximum or peak plasma concentration (Cmax) for Makena® subcutaneous was slightly higher than for the intramuscular (7.3 ng/mL compared to 6.3 ng/mL), with the 90 percent confidence interval for the ratio of Cmax (96.6 to 138.7 percent) falling outside of the bioequivalence range of 80 to 125 percent. Based on the findings from this study, Amag Pharmaceuticals plans to submit a supplemental new drug application to the FDA for the Makena® subcutaneous auto-injector in the second quarter of 2017, with an anticipated decision in the fourth quarter of 2017.
• • On October 12, 2016, Amag Pharmaceuticals announced that the definitive pharmacokinetic study and the comparative pain study for the Makena® (hydroxyprogesterone caproate injection) subcutaneous auto-injector program (Makena SQ) have been initiated with the first patient dosed. The company intends to use the results from the pain study to establish clinical superiority of the SQ auto-injector over the intramuscular injection to support a submission to the FDA for orphan drug exclusivity for the Makena SQ auto-injector. Amag Pharmaceuticals plans to file the sNDA for the Makena SQ auto-injector in the second quarter of 2017 and anticipates a decision on approval in the first quarter of 2018.

Is general: Yes