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Tolerability and efficacy of the monoaminergic stabilizer (−)-OSU6162 (PNU-96391A) in Huntington’s disease: a double-blind cross-over study

Published online by Cambridge University Press:  23 June 2014

Angelica Kloberg ,
Radu Constantinescu ,
Marie Karin Lena Nilsson ,
Maria Lizzie Carlsson ,
Arvid Carlsson ,
Jan Wahlström  and
Sara Haghighi
Angelica Kloberg*
Affiliation:
A Carlsson Research AB, Sahlgrenska Science Park, Gothenburg, Sweden
Radu Constantinescu
Affiliation:
Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden
Marie Karin Lena Nilsson
Affiliation:
Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Maria Lizzie Carlsson
Affiliation:
Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Arvid Carlsson
Affiliation:
Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Jan Wahlström
Affiliation:
Department of Medical and Clinical Genetics, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Sara Haghighi
Affiliation:
Department of Neurology, Sahlgrenska University Hospital, Gothenburg/Skaraborg Hospital, Skövde, Sweden
*
Dr. Angélica Kloberg, PhD, A Carlsson Research AB, Sahlgrenska Science Park, Medicinaregatan 8A, vån 2, lab SE 413 46 Gothenburg, Sweden. Tel: +46-31-7411892; E-mail: angelica.kloberg@carlssonresearch.eu
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Abstract

Objective

To evaluate the safety (primary objective) and efficacy (secondary objective) of (−)-OSU6162 in Huntington’s disease (HD).

Methods

In a double-blind, cross-over trial, patients with HD were randomly assigned to start treatment on either (−)-OSU6162 or placebo. After 4 weeks, those patients who initially received active drug were switched to placebo for another 4 weeks, and vice versa. During the first week the (−)-OSU6162 dose was 15 mg twice daily, during the second week 30 mg twice daily, and during the last 2 weeks 45 mg twice daily. Motor, cognitive, mental and social functions were rated by the clinical investigator or by self-assessment, using established rating scales.

Results

Fifteen patients fulfilling inclusion and exclusion criteria completed the study. (−)-OSU6162 was well tolerated by all patients and no adverse effects were observed. (−)-OSU6162 treatment significantly improved the Short Form 36 Vitality score, mainly due to an improvement of the individual item ‘worn-out’ (VT3). In addition, an improvement of depressive symptoms was found using Beck Depression Inventory. In contrast to a general trend of improvement in several non-motor variables only small and non-significant differences between (−)-OSU6162 and placebo were found regarding motor functions.

Conclusions

(−)-OSU6162 offers promise for the treatment of HD, as a drug with good tolerability, capable of improving the patients’ experienced non-motor functions such as energy and mood and thus alleviating symptoms of great importance for their quality of life.

Keywords

depressionhuntington’s diseasemonoaminergic stabilizervitality
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 26 , Issue 5 , October 2014 , pp. 298 - 306
Copyright
© Scandinavian College of Neuropsychopharmacology 2014 

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Footnotes

†

Deceased

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