A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Investigate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of JNJ-39588146 in Subjects With Heart Failure

The purpose of this study is to investigate the safety, tolerability, pharmacodynamics (how the study medication affects the body) and pharmacokinetics (how the drug is absorbed in the body, how it is distributed within the body and removed from the body over time) of an intravenous administration of JNJ-39588146 or placebo over a 3-hour period in patients with heart failure. The highest tolerated dose received during the first 3 hours of the study will be administered to some patients for an additional 18 hours. There will be up to 3 doses given throughout the administration period over a total of up to 21 hours.

Start Date01 Jun 2010

Sponsor / Collaborator

Johnson & Johnson Pharmaceutical Research & Development LLC

100 Clinical Results associated with Stresscopin

100 Translational Medicine associated with Stresscopin

100 Patents (Medical) associated with Stresscopin

Literatures (Medical) associated with Stresscopin

01 Sep 2013·Regulatory Peptides

Intracerebroventricular injection of stresscopin-related peptide enhances cardiovascular function in conscious rats

Article

Author: De-Lai Qiu ; Mei-Zi Li ; Ri-Long Piao ; Hiroshi Kannan ; Ri Jin ; Yan-Hua Bing ; Ying-Jun Li ; Qing-Hua Jin ; Chun-Ping Chu

Stresscopin-related peptide (SRP), which is a member of the corticotropin-releasing factor (CRF) family, is a high-affinity ligand for the type 2 corticotropin-releasing factor receptor (CRF-R2) and is involved in stress-coping responses. Central treatment with SRP suppresses food intake, delays gastric emptying and decreases heat-induced edema, but the effects of central administration of SRP on the cardiovascular system are unclear. Here we examined the effects of intracerebroventricular (i.c.v.) administration of SRP on cardiovascular function, and compared the cardiovascular effects of SRP and stresscopin (SCP). Our results showed that i.c.v. administration of SRP (0.5nmol) increased mean arterial blood pressure (MABP) and heart rate (HR), but failed to increase plasma norepinephrine and epinephrine levels. Compared with an equivalent dose of SCP, the area under the curve (AUC) values for the changes in MABP and HR were significantly smaller with SRP, indicating that the cardiovascular effects of SRP were weaker than those mediated by SCP. Pre-treatment with a selective CRF-R2 antagonist, antisauvagine-30 (4nmol, i.c.v.) abolished the SRP and SCP induced changes in MABP and HR. These results indicate that central administration of SRP induces a weaker enhancement of cardiovascular function through CRF-R2 than that induced by SCP and that these effects are mediated without increasing plasma norepinephrine and epinephrine levels.

01 Jun 2013·European Journal of Heart FailureQ1 · MEDICINE

Haemodynamic effects, safety, and pharmacokinetics of human stresscopin in heart failure with reduced ejection fraction†

Q1 · MEDICINE

Article

Author: Deckelbaum, Lawrence I. ; Macarie, Cezar ; Ghosh, Atalanta ; Koester, Andreas ; Bubenek‐Turconi, Serban‐Ion ; Radziszewski, Waldemar ; Olson, Allan ; Konstam, Marvin A. ; Li, Lilian Y. ; Greene, Stephen J. ; Patel, Ayan R. ; Korewicki, Jerzy ; Maggioni, Aldo P. ; Bueno, Orlando F. ; Gheorghiade, Mihai ; Grzybowski, Jacek ; Metra, Marco ; Ponikowski, Piotr

AimsHuman stresscopin is a corticotropin‐releasing factor (CRF) type 2 receptor (CRFR2) selective agonist and a member of the CRF peptide family. Stimulation of CRFR2 improves cardiac output and left ventricular ejection fraction (LVEF) in patients with stable heart failure (HF) with reduced LVEF. We examined the safety, pharmacokinetics, and effects on haemodynamics and serum biomarkers of intravenous human stresscopin acetate (JNJ‐9588146) in patients with stable HF with LVEF ≤35% and cardiac index (CI) ≤2.5 L/min/m2.Methods and resultsSixty‐two patients with HF and LVEF ≤35% were instrumented with a pulmonary artery catheter and randomly assigned (ratio 3:1) to receive an intravenous infusion of JNJ‐9588146 or placebo. The main study was an ascending dose study of three doses (5, 15, and 30 ng/kg/min) of study drug or placebo administered in sequential 1 h intervals (3 h total). Statistically significant increases in CI and reduction in systemic vascular resistance (SVR) were observed with both the 15 ng/kg/min (2 h time point) and 30 ng/kg/min (3 h time point) doses of JNJ‐9588146 without significant changes in heart rate (HR) or systolic blood pressure (SBP). No statistically significant reductions in pulmonary capillary wedge pressure (PCWP) were seen with any dose tested in the primary analysis, although a trend towards reduction was seen.ConclusionIn HF patients with reduced LVEF and CI, ascending doses of JNJ‐9588146 were associated with progressive increases in CI and reductions in SVR without significant effects on PCWP, HR, or SBP.Trial registration: NCT01120210

01 May 2009·PeptidesQ3 · MEDICINE

In vivo evidence for ligand-specific receptor activation in the central CRF system, as measured by local cerebral glucose utilization

Q3 · MEDICINE

Article

Author: Xavier Langlois ; Geoffrey Warnock ; Thomas Steckler ; Dieder Moechars

Corticotropin-releasing factor (CRF) is well known for its role in the hypothalamic-pituitary-adrenocortical (HPA) axis and its involvement in stress and anxiety. CRF acts via two main receptor subtypes, CRF(1) and CRF(2). Other endogenous CRF-related peptide ligands are the Urocortins 1 and 2 and Stresscopin. While CRF is thought to mediate its anxiogenic-like properties through CRF(1), the role of CRF(2) and its endogenous ligands Urocortin 2 and Stresscopin are less clear, with a suggested role in mediating the delayed effects of stress. Measurement of local cerebral glucose utilization (LCGU) provides an estimate of neuronal activity, and is of potential use as a translational tool in comparison to FDG PET. We hypothesized that comparison of the patterns of metabolic changes induced by CRF-related peptides could provide further information on their role in the brain. The present studies examined the effects of CRF-related peptides on LCGU, and the role of CRF(1) and CRF(2) in the CRF-induced LCGU response. CRF induced increases in LCGU in hypothalamic, thalamic, cerebellar and hippocampal regions, and further studies using antagonists or mutant mice lacking a functional CRF(1) receptor clearly suggested a role for CRF(2) in this effect. Urocortin 1 increased LCGU in a dissected hindbrain region. However, central administration of the CRF(2)-selective agonists Urocortin 2 and Stresscopin failed to affect LCGU, which may suggest ligand-dependent receptor activation within the CRF system. The present data supports a role for CRF(2) in the regulation of neuronal glucose metabolism.

100 Deals associated with Stresscopin

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Indication	Highest Phase	Country/Location	Organization	Date
Heart Failure	Phase 2	RO	Johnson & Johnson Pharmaceutical Research & Development LLC	01 Jun 2010
Heart Failure	Phase 2	PL	Johnson & Johnson Pharmaceutical Research & Development LLC	01 Jun 2010
Heart Failure	Phase 2	DE	Johnson & Johnson Pharmaceutical Research & Development LLC	01 Jun 2010
Heart Failure	Phase 2	BE	Johnson & Johnson Pharmaceutical Research & Development LLC	01 Jun 2010

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01120210 (CTgov)	Phase 2	Heart Failure	62	placebo+JNJ-39588146 (Placebo)	wopzzszbzk(fgxpciylrn) = xzfqunclxe rxgdggbkcr (vvqveuinhn, snhkhhlndz - kzdpaibmxz) View more	-	25 Jun 2013
				JNJ-39588146 (JNJ-39588146)	wopzzszbzk(fgxpciylrn) = xhizcllutn rxgdggbkcr (vvqveuinhn, seqfbvwbor - ardcuwepjb) View more

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