Een gerandomiseerd, dubbelblind, placebo-gecontrolleerd fase 1 onderzoek ter bestudering van de veiligheid, verdraagbaarheid, farmacokinetiek en farmacodynamiek van enkelvoudig opklimmende P1201-07 doseringen in gezonde vrijwilligers met overgewicht

It is well known that an increase in the transmission of serotonin (also known
as 5 hydroxytryptamine (5-HT)), in the brain regulates feeding habits by
inducing a reduction in food intake. Earlier appetite suppressants such as
fenfluramine and d-fenfluramine were found to reduce the food intake in both
rats and humans primarily by blocking the 5-HT reuptake in the neuronal synapse
and also causing a 5-HT release from the synapse. Data from human studies
corroborated laboratory findings, indicating that there was a direct effect in
decreasing food intake with enhanced satiety when the neuronal 5-HT receptors
were pharmacologically stimulated.
Hence, 5-HT2C receptor agonist programs are developed to identify and
characterize a highly selective 5-HT2C receptor agonist and to test the
hypothesis that oral treatment with this agent will lead to sustained weight
loss (fat loss) in obese patients, which in turn will result in an improvement
in co-morbid risk factors.

The clinical candidate, P1201-07 is an orally active compound with selective
5-HT2C receptor agonist properties.

To determine the safety and tolerability of P1201-07 administered as single
ascending oral doses in overweight or obese but otherwise healthy subjects.

A single-centre, randomized, double-blind, placebo-controlled study with single
ascending doses in 2 cohorts of 8 overweight or obese but otherwise healthy
male or female subjects. Each cohort may participate in up to 4 periods in an
alternating fashion, with 6 subjects receiving a single oral dose of P1201-07
each period and 2 subjects receiving a single oral dose of placebo each period.

Single doses of P1201-07

Compound; reduction in food consumption and body weight, red staining of the
mouth, nostrils and eyes, poor grooming and noisy respiration, decreased motor
activity, decrease in body temperature, increase in heart rate and blood
pressure.
Similar drugs that are marketed have demonstrated effects such as nauseau,
vomiting and headache.


Procedures: The insertion of the indwelling canula and the venepuncture may
cause pain, and lead to a bruise. Light bleeding and possibly an infection. The
use of ECG (heart trace) gel/electrodes on the skin may cause allergy or skin
reactions. Some discomfort may be experienced due to the intake of the high fat
meal on day 1 of each period.