A Phase IIa, randomized, double-blind, placebo-controlled, multi-center study to evaluate the safety, tolerability, and effects of AZP-531, an Unacylated Ghrelin analog, on food-related behavior in patients with Prader-Willi Syndrome

Start Date01 Oct 2015

Sponsor / Collaborator

Alizé Pharma SARL

EUCTR2014-001670-34-IT / Not yet recruitingNot Applicable

Start Date31 Aug 2015

Sponsor / Collaborator

Alizé Pharma SARL

NCT02040012 / Unknown statusPhase 1

A Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZP-531 in Healthy Volunteers, Overweight/Obese Volunteers and Patients With Type 2 Diabetes Mellitus

Objectives:
Primary Objectives
To investigate the safety and tolerability of single ascending doses of AZP- 531 in healthy volunteers.
To investigate the safety and tolerability of single and multiple ascending doses of AZP-531 in overweight/obese volunteers.
To investigate the safety and tolerability of single and multiple ascending doses of AZP-531 in patients with type 2 diabetes mellitus.
Secondary Objectives • To determine the plasma pharmacokinetic (PK) profile of AZP-531 after single and multiple doses.
Exploratory Objectives
• To obtain exploratory data on the effects of AZP-531 on the pharmacodynamic (PD) markers of blood glucose, interstitial glucose, insulin, and plasma acylated ghrelin (AG) and unacylated ghrelin (UAG)

Start Date01 Jul 2013

Sponsor / Collaborator

Alizé Pharma SARL

100 Clinical Results associated with Alizé Pharma SARL

0 Patents (Medical) associated with Alizé Pharma SARL

Literatures (Medical) associated with Alizé Pharma SARL

01 Jan 2017·Basic Research in CardiologyQ1 · MEDICINE

Unacylated ghrelin analog prevents myocardial reperfusion injury independently of permeability transition pore

Q1 · MEDICINE

Article

Author: Allas, Soraya ; Loufouat, Joseph ; Abribat, Thierry ; Gallo-Bona, Noelle ; Pillot, Bruno ; Harisseh, Rania ; Ferrera, René ; Delale, Thomas ; Crola Da Silva, Claire ; Ovize, Michel ; Augeul, Lionel ; Gharib, Abdallah

Reperfusion injury is responsible for an important part of myocardial infarct establishment due notably to triggering cardiomyocytes death at the first minutes of reperfusion. AZP-531 is an optimized analog of unacylated ghrelin currently in clinical development in several metabolic diseases. We investigated a potential cardioprotective effect of AZP-531 in ischemia/reperfusion (IR) and the molecular underlying mechanism(s) involved in this protection. In vivo postconditioning with AZP-531 in C57BL6 mouse IR model decreased infarct size. Western blot analysis on areas at risk from the different mouse groups showed that AZP-531 activates Akt, ERK1-2 as well as S6 and 4EBP1, mTORC1 effectors. We also showed an inhibition of caspase 3 cleavage and Bax translocation to the mitochondria. AZP-531 also stimulated the expression of antioxidants and was capable of decreasing mitochondrial H₂O₂ production, contributing to the reduction of ROS accumulation. AZP-531 exhibits cardioprotective effect when administrated for postconditioning in C57BL6 mouse IR model. Treatment with AZP-531 rescued the myocardium from cell death at early reperfusion by stimulating protein synthesis, inhibiting Bax/caspase 3-induced apoptosis as well as ROS accumulation and oxidative stress-induced necrosis. AZP-531 may prove useful in the treatment of IR injury.

01 Dec 2015·EndocrineQ3 · MEDICINE

Elevated ratio of acylated to unacylated ghrelin in children and young adults with Prader–Willi syndrome

Q3 · MEDICINE

Article

Author: Faye, S ; Allas, S ; Diène, G ; Kuppens, R J ; Bakker, N E ; Tauber, M ; Delhanty, P J D ; Julien, M ; Nicolino, M ; Delale, T ; Bernoux, D ; Hokken-Koelega, A C S ; van der Lely, A J ; Molinas, C

Prader-Willi syndrome (PWS) is characterized by a switch from failure to thrive to excessive weight gain and hyperphagia in early childhood. Hyperghrelinemia may be involved in the underlying mechanisms of the switch. The purpose of this study is to evaluate acylated ghrelin (AG) and unacylated ghrelin (UAG) levels in PWS and investigate their associations with hyperphagia. This is a cross-sectional clinical study conducted in three PWS expert centers in the Netherlands and France. Levels of AG and UAG and the AG/UAG ratio were determined in 138 patients with PWS (0.2-29.4 years) and compared with 50 age-matched obese subjects (4.3-16.9 years) and 39 healthy controls (0.8-28.6 years). AEBSF was used to inhibit deacylation of AG. As a group, PWS patients had higher AG but similar UAG levels as healthy controls (AG 129.1 vs 82.4 pg/ml, p = 0.016; UAG 135.3 vs 157.3 pg/ml, resp.), resulting in a significantly higher AG/UAG ratio (1.00 vs 0.61, p = 0.001, resp.). Obese subjects had significantly lower AG and UAG levels than PWS and controls (40.3 and 35.3 pg/ml, resp.), but also a high AG/UAG ratio (1.16). The reason for the higher AG/UAG ratio in PWS and obese was, however, completely different, as PWS had a high AG and obese a very low UAG. PWS patients without weight gain or hyperphagia had a similar AG/UAG ratio as age-matched controls, in contrast to those with weight gain and/or hyperphagia who had an elevated AG/UAG ratio. The switch to excessive weight gain in PWS seems to coincide with an increase in the AG/UAG ratio, even prior to the start of hyperphagia.

01 Apr 2015·DiabetesQ1 · MEDICINE

Unacylated Ghrelin Induces Oxidative Stress Resistance in a Glucose Intolerance and Peripheral Artery Disease Mouse Model by Restoring Endothelial Cell miR-126 Expression

Q1 · MEDICINE

Article

Author: Togliatto, Gabriele ; Brizzi, Maria Felice ; Delale, Thomas ; Cotogni, Paolo ; Dentelli, Patrizia ; Ghigo, Ezio ; Falcioni, Rita ; Trombetta, Antonella ; Granata, Riccarda ; Gallo, Sara ; Rosso, Arturo

Reactive oxygen species (ROS) are crucial in long-term diabetes complications, including peripheral artery disease (PAD). In this study, we have investigated the potential clinical impact of unacylated ghrelin (UnAG) in a glucose intolerance and PAD mouse model. We demonstrate that UnAG is able to protect skeletal muscle and endothelial cells (ECs) from ROS imbalance in hind limb ischemia–subjected ob/ob mice. This effect translates into reductions in hind limb functional impairment. We show that UnAG rescues sirtuin 1 (SIRT1) activity and superoxide dismutase-2 (SOD-2) expression in ECs. This leads to SIRT1-mediated p53 and histone 3 lysate 56 deacetylation and results in reduced EC senescence in vivo. We demonstrate, using small interfering RNA technology, that SIRT1 is also crucial for SOD-2 expression. UnAG also renews micro-RNA (miR)-126 expression, resulting in the posttranscriptional regulation of vascular cell adhesion molecule 1 expression and a reduced number of infiltrating inflammatory cells in vivo. Loss-of-function experiments that target miR-126 demonstrate that miR-126 also controls SIRT1 and SOD-2 expression, thus confirming its role in driving UnAG-mediated EC protection against ROS imbalance. These results indicate that UnAG protects vessels from ROS imbalance in ob/ob mice by rescuing miR-126 expression, thus emphasizing its potential clinical impact in avoiding limb loss in PAD.

100 Deals associated with Alizé Pharma SARL

100 Translational Medicine associated with Alizé Pharma SARL

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