MK-0777-Merck : Hope for Schizophrenia or Generalized Anxiety Disorder? Neurocognition in Schizophrenia: Cataracts, side effect, NIH trial completed

Follow up to my original post (re-posted below) from

Tuesday, October 21, 2008

The drug trial below for Generalized Anxiety Disorder is now complete as of clinical trials website September 30, 2009.

MK-0777- Merck:Hope for Schizophrenia or Generalized Anxiety Disorder? Neurocognition in Schizophrenia : Cataracts, side effect - October 21, 2008, soulful sepulcher blog

From:

Treatment Study for Cognitive Deficits in Schizophrenia (TURNS)

"The standard of care for schizophrenia is antipsychotic medications to treat psychotic symptoms. However, cognitive impairments remain and these impairments have been found to be significantly associated with the poor psychosocial function observed in patients with schizophrenia. There is a considerable preclinical rationale for the use of drugs that act at the GABAA α2 subunit as adjunctive treatments to target cognitive impairments. MK-0777 provides an opportunity to directly test this mechanism.The purpose of the proposed study is to examine the efficacy and safety of two doses of MK-0777 GEM, 3 mg BID and 8 mg BID, in the treatment of cognitive impairments in patients with schizophrenia. Secondary goals are to determine whether MK-0777 has beneficial effects on measures of functional capacity and patient self-report of cognitive function."

Responsible Party:
University of California, Los Angeles ( Stephen R. Marder, M.D. )
Study ID Numbers: TURNS02, HHSN 278200441003C
First Received: July 19, 2007
Last Updated: June 3, 2008

ClinicalTrials.gov Identifier: NCT00505076

Health Authority: United States: Food and Drug Administration
Keywords provided by University of California, Los Angeles:
Cognition
Schizophrenia
Study placed in the following topic categories:
SchizophreniaMental Disorders
Psychotic Disorders
Schizophrenia and Disorders with Psychotic Features
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A Study of MK0777 Gel Extrusion Module (GEM) in the Treatment of Outpatients With Generalized Anxiety Disorder. (study now completed)

Sponsors and Collaborators
Merck
Investigators
Study Director: Medical Monitor Merck

More Information

Responsible Party: Merck & Co., Inc.
( Executive Vice President, Clinical and Quantitative Sciences )
Study ID Numbers: 2007_630,
MK0777-019
First Received: June 22, 2008
Last Updated: June 23, 2008
ClinicalTrials.gov Identifier: NCT00703833
Health Authority: United States: Food and Drug AdministrationStudy placed in the following topic categories:
Anxiety Disorders
Mental Disorders
Additional relevant MeSH terms:Pathologic ProcessesDisease

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MK-0777 for the Treatment of Cognitive Impairments in Patients with Schizophrenia.

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From

Department of Psychiatry at Columbia University Medical Center

"The present study is part of TURNS (Treatment Units for Research in Neurocognition in Schizophrenia), a NIMH-funded contract for the evaluation of new compounds for the treatment of cognitive impairments in schizophrenia (P.I.: Steve Marder, M.D.). NYSPI is one of seven sites designated to conduct these neurocognitive trials. The PI for this particular study and compound (MK-0777) is Dr: Robert W. Buchanan, M.D. (Maryland Psychiatric Research Center). Cognitive symptoms of schizophrenia have been linked to impairment in social and occupational functioning. In spite of recent advances in the pharmacological treatment of the illness, little progress has been made in the search for effective treatments for these cognitive deficits. Conventional antipsychotics have limited effects on these impairments. Second generation antipsychotics may have modest benefits for cognitive function, but whether this represents a direct cognitive enhancing effect has not been established. Regardless, patients continue to exhibit pronounced cognitive impairments despite adequate second generation antipsychotic treatment. Adjunctive pharmacotherapy may offer a viable approach for the treatment of cognitive impairments.

Gamma-amino-butyric acid (GABA) is the major inhibitory neurotransmitter in the CNS. GABAergic mechanisms are important for the regulation of prefrontal cortical function and they are thought to play a major role in working memory, through their modulation of glutamatergic function in the dorsolateral prefrontal cortex (DLPFC). MK-0777 is a GABAA α2/α3 partial agonist with virtually no activity at the α1 and α5 subunits.

Therefore, it is less likely to cause the level of sedation observed with benzodiazepines, which act at the α1 subunit. MK-0777 has no known activity at any other receptor.

MK-0777 was developed as a treatment for Generalized Anxiety Disorder, but development was terminated because of the observation that MK-0777 caused cataracts in rodent long-term toxicology assays. Subjects will be monitored for cataracts throughout the proposed study.

There are two MK-0777 formulations: i) immediate release (IR); and ii) a controlled-release formulation which will be used in this study (Gel Extrusion Module, GEM). The proposed study is a multicenter, randomized, double blind comparison of MK-0777 GEM 3 mg BID, MK-0777 GEM 8 mg BID, and placebo added to ongoing stable antipsychotic treatment in schizophrenia patients."

Location: 1051 Riverside Dr.-Unit 4 New York, NY 10032
Clinic: Lieber Schizophrenia Research Clinic
Division: Therapeutics
Study chairs or principal investigators:
Jeffrey Lieberman M.D.,
Principal InvestigatorCo-investigators:
Roberto Gil,
Jill Harkavy-Friedman,
David Kimhy,
Fred Jarskog

Researching for treatment for schizophrenia:

Jeffery Lieberman, MD.