STUDY TO INVESTIGATE THE EFFECT OF RO5186582 ON RENAL TRANSPORTER
Research type
Research Study
Full title
A NON-RANDOMIZED, OPEN-LABEL, TWO TREATMENT, TWO PERIOD, FIXED SEQUENCE CROSSOVER STUDY TO INVESTIGATE THE EFFECT OF RO5186582 TREATMENT ON RENAL TRANSPORTER ACTIVITY IN HEALTHY VOLUNTEERS
IRAS ID
168180
Contact name
Jim Bush
Contact email
Sponsor organisation
F. Hoffmann-La Roche Ltd
Eudract number
2014-001851-21
Duration of Study in the UK
0 years, 2 months, 5 days
Research summary
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 at these receptors is inhibitory which means it reduces cognitive and memory function. RO5186582 reduces the effect of GABA on its receptor and therefore could potentially improve cognitive function and memory, therefore being developed to help people with downs syndrome.
RO5186582 treatment causes reversible, dose-related increase in serum creatinine (a marker of kidney function) and corresponding dose-related decrease in estimated creatinine clearance (CLcr) (the rate of elimination of creatinine).
The main purpose of this study is to investigate the effect of RO5186582 on some molecules which help in the transport of chemicals across the membranes involved in blood filtration in kidney. Metformin (a drug used to treat type 2 diabetes) is considered as one of the best molecule to study this effect, because metformin is a typical compound transported through this mechanism, especially by transporter molecules OCT2 and Mate1.
One of the other intentions of this study is to investigate the effect of RO5186582 on kidney function. One of the methods to assess this is by the estimation of GFR. To measure GFR (Glomerular Filtration Rate) ie the volume of blood filtered in a given period of time, a dose of 1.5 gram the Iodine administered intravenously as a 5 ml solution. Iohexol (An iodine compound) is widely used in clinical practice for imaging procedure and this dose is significantly lower than the dose used for imaging purposes.
One of the other estimation of renal function is through the assessment of effective renal plasma flow ie the amount of plasma passing through the kidney tubules per unit time. For this purpose a compound, Para-aminohippurate (PAH), which is filtered by the kidneys and then actively secreted to the kidney tubules is used. It is available as an injectable solution.REC name
London - Brent Research Ethics Committee
REC reference
14/LO/2059
Date of REC Opinion
3 Dec 2014
REC opinion
Favourable Opinion