Caution - Investigational Drug; Limited by United States Law to Investigational use only.
Caution - Investigational Drug; Limited by United States Law to Investigational use only.
SIRIUS I and II

SIRIUS I and II

SIRIUS I (Phase IIa)

Ularitide has been studied for the treatment of acute heart failure (AHF) in two double-blind, placebo-controlled Phase I1 and Phase II2 studies (Safety and efficacy of an Intravenous placebo controlled Randomised Infusion of Ularitide in a prospective double – blind Study in patients with symptomatic, decompensated chronic heart failure – SIRIUS I and SIRIUS II).

Study design

SIRIUS I was a randomised, double-blind, ascending-dose study. Twenty four patients with AHF received 24 hour IV infusion of placebo or ularitide at 7.5, 15, or 30 ng/kg/min in addition to standard therapy.

Key findings

  • In general, a meaningful number of patients in each ularitide group had marked or moderate improvement over baseline in self-assessed dyspnea (breathlessness) at six hours, whereas minimal improvement was observed in the placebo group
  • The proportion of subjects with marked or moderate improvement was greater in the 15 and 30 ng/kg/min groups compared with the 7.5 ng/kg/min group
  • Mortality at Day 30 was 5.6% (1 of 18 patients) across the three ularitide groups and 16.7% (1 of 6 patients) in the placebo group
  • The most frequently reported adverse events (AEs) were hypotension, a confused state, restlessness and dyspnoea

 
 

SIRIUS II (Phase IIb)

Study design

The SIRIUS II study was a placebo controlled, double-blind, parallel-group study, which randomised 221 patients with AHF to one of three different ularitide doses of 7.5 ng/kg/min (n=60), 15 ng/kg/min (n=53) and 30 ng/kg/min (n=55) or to placebo (N=53), which were administered in addition to standard therapy.

Key findings

  • At six hours:
    • All three infusions rates of ularitide produced greater decrease in pulmonary capillary wedge pressure, a key indicator of cardiac function, compared with the placebo group
    • 34.0% of subjects in the placebo group reported no change in dyspnoea as compared to 10.3% to 17.6% in the three ularitide groups
    • A greater proportion of subjects in the 7.5, 15, and 30 ng/kg/min dose (39.7%, 47.1% and 45.5%, respectively) reported a marked or moderate improvement over baseline in self-assessed dyspnoea compared with subjects in the placebo group (24.5%), p <0.05 for each dose versus placebo
  • The median time of hospitalisation was shorter for the 15 ng/kg/min and 30 ng/kg/min groups (122 and 158 hours, respectively) compared with the placebo and the 7.5 ng/kg/min groups (201 and 192 hours, respectively)
  • Mortality at Day 30 was 3% across the three ularitide dose groups compared to 13.2% for the placebo group
  • The most frequent drug-related AEs across the three ularitide groups were hypotension and dose-dependent decreases in blood pressure (BP)
    • Decreases in BP were seen between four to 12 hours after start of dosing and about half were asymptomatic

References

1. Mitrovic V, Lüss H, Nitsche K, et al. Effects of the renal natriuretic peptide urodilatin (ularitide) in patients with decompensated chronic heart failure: A double-blind, placebo-controlled, ascending-dose trial. Am Heart J. 2005;150:1239.e1-1239.e8. 

2. Mitrovic V, Seferovic P, Simeunovic D, et al. Haemodynamic and clinical effects of ularitide in decompensated heart failure. Euro Heart J 2006; 27, 2823-2832.