rget dosage of 60 mcg/kg/hour (patientsreceived 30 mcg/kg/hour for 4 hours, 60 mcg/kg/hour for 52 hours, then 30 mcg/kg/hour for
4 hours) was also eva luated in Study 1.
Demographic and baseline disease characteristics were generally similar across treatment groupsin the pooled Studies 1 and 2. Most patients were White (63%) or Black (34%); 18% of patientsidentified as Hispanic or Latina; the average age of women receiving ZULRESSO was 28 years.
Most patients (76%) had onset of PPD symptoms within 4 weeks after delivery, with theremainder having onset during the third trimester. Baseline oral antidepressant use was reportedfor 23% of patients.
The primary endpoint was the mean change from baseline in depressive symptoms as measuredby the HAM-D total score at the end of the infusion (Hour 60). A pre-specified secondaryefficacy endpoint was the mean change from baseline in HAM-D total score at Day 30. In bothplacebo-controlled studies, titration to a target dose of ZULRESSO 90 mcg/kg/hour was superiorto placebo in improvement of depressive symptoms. In a group of 38 patients in Study 1, aZULRESSO titration to a target dose of 60mcg/kg/hour was also superior to placebo inimprovement of depressive symptoms.
Table 3: Results for the Primary Endpoint – HAM-D Total Score (Studies 1 and 2)
Study
Number
Treatment Group
(# ITT subject)
Primary Endpoint: Change from Baseline in HAM-D Total
Score at Hour 60
Mean Baseline
Score (SD)
LS Mean
Change from
Baseline (SE)
Placebo-subtracted
Difference (95% CI)
Unadjusted p-value
1 ZULRESSO target dosage
90 mcg/kg/hour (n=41)*
Placebo (n=43)
28.4 (2.5)
28.6 (2.5)
-17.7 (1.2)
-14.0 (1.1)
-3.7 (-6.9, -0.5)
P=0.0252
ZULRESSO target dosage
60 mcg/kg/hour (n=38)*
Placebo (n=43)
29.0 (2.7)
28.6 (2.5)
-19.5 (1.2)
-14.0 (1.1)
-5.5 (-8.8, -2.2)
P=0.0013
2 ZULRESSO target dosage
90 mcg/kg/hour (n=51)*
Placebo (n=53)
22.6 (1.6)
22.7 (1.6)
-14.6 (0.8)
-12.1 (0.8)
-2.5 (-4.5, -0.5)
P=0.0160
HAM-D: Hamilton depression rating scale; ITT: intention to treat; SD: standard deviation; LS: least squaresSE: standard error; CI: confidence interval; *: statistically significant after multiplicity adjustmentsExamination of subgroups by race did not suggest differences in response.
Time Course of Treatment Response
Figure 1 shows the time course of response for the ZULRESSO 90 mcg/kg/hour-target and60 mcg/kg/hour-target groups compared to the placebo group for Study 1.
Figure 1: Change from Baseline in HAM-D Total Score Over Time (Days) in Study 1*ZULRESSO was administered via a 60-hour intravenous infusion as follows:
90 mcg/kg/hour-target dosage: 30 mcg/kg/hour for 4 hours, 60 mcg/kg/hour for 20 hours, 90 mcg/kg/hour for 28 hours,
60 mcg/kg/hour for 4 hours, 30 mcg/kg/hour for 4 hours
60 mcg/kg/hour-target dosage: 30 mcg/kg/hour for 4 hours, 60 mcg/kg/hour for 52 hours, 30 mcg/kg/hour for 4 hours
16 HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
ZULRESSO injection is supplied as 100 mg brexanolone in 20 mL (5 mg/mL) single-dose vialscontaining a sterile, preservative-free, clear, colorless solution. NDC 72152-547-20
Storage and Handling
Store the undiluted ZULRESSO product at 2°C to 8°C (36°F to 46°F). Do not freeze. Storeprotected from light.
The diluted product in the infusion bag can be used at room temperature for up to 12 hours. If the |
