ts had other forms of distributive shock such as neurogenic shock. At the time of study drug administration, 97% of subjects were receiving norepinephrine, 67% vasopressin, 15% phenylephrine, 13% epinephrine, and 2% dopamine. 83% of subjects had received two or more vasopressors and 47% three or more vasopressors prior to study drug administration. 61% of subjects were male, 80% were White, 10% were Black, and 10% were other races. The median age of subjects was 64 years (range: 22-89 years). Patients requiring high doses of steroids, patients with a history of asthma or bronchospasm, and patients with Raynaud's syndrome were not included.
The primary endpoint was achieved by 70% of patients randomized to GIAPREZA compared to 23% of placebo subjects; p < 0.0001 (a treatment effect of 47%). Figure 1 shows the results in all patients and in selected subgroups.
Figure 1: ATHOS-3: Primary Endpoint – Overall Result and Results in Selected Subgroups
Figure 1
NE Equiv = norepinephrine equivalent dose: the sum of all vasopressors doses with each vasopressor dose converted to the clinically equivalent norepinephrine dose
Note: The figure above presents effects in various subgroups, all of which are baseline characteristics. The 95% confidence limits that are shown do not take into account the number of comparisons made, and may not reflect the effect of a particular factor after adjustment for all other factors. Apparent homogeneity or heterogeneity among groups should not be over-interpreted.
In the GIAPREZA-treated group, the median time to reach the target MAP endpoint was 5 minutes. The effect on MAP was sustained for at least the first three hours of treatment. The median dose of GIAPREZA was 10 ng/kg/min at 30 minutes. Of the 114 responders at Hour 3, only 2 (1.8%) received more than 80 ng/kg/min.
Patients were not necessarily on maximum doses of other vasopressors at the time of randomization. The effect of GIAPREZA when added to maximum doses of other vasopressors is unknown.
Mortality through Day 28 was 46% on GIAPREZA and 54% on placebo (hazard ratio 0.78; 95% confidence interval 0.57 – 1.07).
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16. HOW SUPPLIED/STORAGE AND HANDLING
16.1. How Supplied
GIAPREZA (angiotensin II) Injection is a clear, aqueous solution for administration by intravenous infusion supplied as a single dose vial in two strengths:
2.5 mg/mL vial: NDC 68547-501-02: A carton of one 1 mL single dose vial containing 2.5 mg angiotensin II (as a sterile liquid).
5 mg/2 mL vial: NDC 68547-002-05: A carton of one 2 mL single dose vial containing 5 mg (2.5 mg/mL) angiotensin II (as a sterile liquid).
16.2. Storage and Handling
GIAPREZA vials should be stored in the refrigerator (36-46°F, 2-8°C).
Discard prepared diluted solution after 24 hours at room temperature or under refrigeration.
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SPL UNCLASSIFIED SECTION
Manufactured for:
La Jolla Pharmaceutical Company
San Diego, CA 92121
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Package Label – 1 mL Single-Dose Vial Label
1ml-vial
1ml-vial
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Package Label – 1 mL Single Vial Carton Label
1ml-vial-carton
1ml-vial-carton
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