Neurogen Corporation announced that, as planned, it commenced a phase 2/3 clinical trial in chronic insomnia patients with the company's insomnia agent, adipiplon and that, based upon reports from initial dosing of a higher than anticipated rate of unwanted next day effects, the company has suspended dosing in the study. Neurogen believes that the bilayer tablet formulation of adipiplon being used in the study may not be performing as expected.
The company plans additional investigation of the bilayer tablet before proceeding further. In prior studies Neurogen has simultaneously administered various doses of both immediate release and controlled release forms of adipiplon. The current study is the first trial in which it has used the two forms laminated together into one bilayer tablet. In previous testing in over 600 subjects, adipiplon has been well tolerated.
"We are disappointed by this setback," said Stephen R. Davis, Neurogen's president and CEO. "We do not yet know whether there is a path forward with lower doses of the existing formulation or whether further formulation development would be required. Until we further assess the situation and determine whether there is a path forward we can and should take, we will carefully limit our resource commitments to this programme. We remain focused on our ongoing phase 2 studies with our dopamine partial agonist, aplindore, in Parkinson's disease and in restless legs syndrome," Davis continued.
Adipiplon has been tested in phase 1 and 2 studies in over 600 subjects for the treatment of insomnia, demonstrating statistical significance compared to placebo on primary endpoints for sleep initiation and maintenance in patients with chronic insomnia. Adipiplon has also demonstrated statistical significance compared to placebo for self-reported quality of sleep in all completed Phase 2 studies to date. Additionally, in studies completed to date it has been well tolerated at all doses tested.
The leading prescription drugs approved for treatment of both onset and maintenance symptoms of insomnia work by modulating the gamma-aminobutyric acid (GABA) system of neurotransmitters. GABA is a chemical naturally released in certain parts of the brain to inhibit brain activity. Adipiplon is a partial agonist which preferentially targets the alpha-3 receptor subtype of the GABA-A neurotransmitter system. Neurogen believes this unique profile may provide a wider therapeutic window than that achieved with other insomnia agents.
Neurogen Corporation is a drug development company focusing on small-molecule drugs to improve the lives of patients suffering from disorders with significant unmet medical need, including insomnia, Parkinson's disease, restless legs syndrome (RLS), anxiety and pain.