The Effect Of RO5186582 On CYP3A4
Research type
Research Study
Full title
A nonrandomized, openlabel, five treatment, fixed sequence crossover study to investigate the effect of RO5186582 treatment on CYP3A4 activity in healthy volunteers
IRAS ID
162934
Contact name
Jim Bush
Contact email
Sponsor organisation
F. Hoffmann-La Roche Ltd
Eudract number
2014-001850-41
Duration of Study in the UK
0 years, 1 months, 6 days
Research summary
Down syndrome is the most common chromosomal anomaly with an incidence of 1 in 650 to 1 in 1000 live births per year worldwide. The primary concern here is intellectual disability which impairs the quality of life in these individuals; yet there is no therapeutic agent available to treat this condition. The lifespan of individuals with Down syndrome has increased significantly and more individuals with Down syndrome are active members of the community. Maximising functional potential through development of drug therapies for cognitive deficits is an important goal. In the Ts65Dn mouse model of Down syndrome RO5186582 exhibited cognition-enhancing properties. RO5186582 has been tested in five clinical trials so far, no serious safety concern has been reported in any of these trials.
This is a drug interaction study where we will be assessing if RO5186582 affects the way body handles midazolam (another drug) when they are given at the same time. Midazolam is a rapid-acting benzodiazepine used as a sedating agent, and is primarily metabolised (broken down) by CYP3A (A liver enzyme.) In pre-clinical studies (test tube experiments), RO5186582 weakly inhibited CYP3A4.
The principle aim of this study is therefore to investigate the effects of RO5186582 treatment on the activity of CYP3A4 and CYP3A5 enzymes in vivo (within the body) in order to find out the potential for drug-drug interactions between RO5186582 and CYP3A4/5 substrates (other drugs which are broken down by the same enzyme).
GABA is a signalling chemical in the brain which acts on specific GABA receptors. These receptors are associated with cognition (mental processing and understanding) and memory. The effect of GABA on these receptors is inhibitory which means it reduces cognitive and memory function. RO5186582 decreases the effect of GABA on its receptors and therefore could potentially improve cognitive function and memory. Therefore RO5186582 is being developed with an intention of helping people with down syndrome.
REC name
South Central - Berkshire B Research Ethics Committee
REC reference
14/SC/1222
Date of REC Opinion
19 Sep 2014
REC opinion
Further Information Favourable Opinion