Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2015-000642-35 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
GABA (gamma-aminobutyric acid) is the main inhibitory neurotransmitter in the human brain. For years, drugs that enhance its effects (e.g., benzodiazepines such as diazepam/Valium) have been used to treat various diseases such as epilepsy, insomnia, anxiety or movement disorders. However, the use of these medications is often compromised because of their side effects, such as sleepiness, memory problems, and addiction.
Therefore, effort has been made to develop drugs that act more selectively in the brain to exert the positive therapeutic effects and are devoid of the unwanted side effects. AZD7325 is one of these drugs. It has been tested in more than 700 people and so far proved to be generally well tolerated. Positron emission tomography (PET) study in humans demonstrated that AZD7325 binds to GABA A receptors in the brain after a single dose. Early clinical studies have shown that it has less sedative and cognitive adverse events as compared with a benzodiazepine lorazepam.
The investigators now wish to evaluate if effects of AZD7325 can be objectively measured in healthy volunteers and to establish which of the drug's outcomes could be utilised for further studies in patients with neurological diseases.
The investigators are especially interested in the effects of AZD7325 on manual dexterity and skin sensation of the hand. This can be assessed by a number of simple non-invasive tests of object manipulation and detection of different sensory stimuli such as touch, vibration, or temperature. Recent studies show that healthy individuals who performed better in similar tasks had more GABA in relevant areas of their brain. If performance in these tasks in healthy volunteers can be improved by enhancing GABA effects in the brain with AZD7325, this would create the grounds for the use of this medication to treat symptoms of certain neurological disorders in which motor control and sensation of the hand is impaired (e.g., polyneuropathy).
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 20 mg AZD7325 | Experimental | 10 mg AZD7325 in orange capsule, Size 0, 2 capsules as a single oral dose |
|
| Placebo | Placebo Comparator | 10 mg Microcrystalline cellulose in orange capsule, Size 0, 2 capsules as a single oral dose |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 20 mg AZD7325 | Drug | A single 20 mg oral dose of AZD7325 |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change in peak grip force in an object manipulation task | from baseline at 1, 2, and 3 hours after the study medication |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in parameters of object manipulation in a object manipulation task (grip force rate) | Parameters: grip force rate | from baseline at 1, 2, and 3 hours after the study medication |
| Changes in parameters of object manipulation in a object manipulation task (load force rate) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Martin Koltzenburg, Prof | Institute of Neurology, University College London | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Hospital for Neurology and Neurosurgery | London | WC1N 3BG | United Kingdom |
Not provided
| ID | Term |
|---|---|
| C576237 | 4-amino-8-(2-fluoro-6-methoxy-phenyl)-N-propylcinnoline-3-carboxamide |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo |
| Drug |
A single oral dose |
|
Parameters: load force rate |
| from baseline at 1, 2, and 3 hours after the study medication |
| Changes in parameters of object manipulation in a object manipulation task (static load force) | Parameters: static load force | from baseline at 1, 2, and 3 hours after the study medication |
| Changes in parameters of object manipulation in a object manipulation task (static grip force) | Parameters: static grip force | from baseline at 1, 2, and 3 hours after the study medication |
| Changes in parameters of object manipulation in a object manipulation task (9-hole pegboard test) | Parameters: 9-hole pegboard test | from baseline at 1, 2, and 3 hours after the study medication |
| Changes in performance in the psychophysical tests of cutaneous sensation ("bumps" test) | Parameters: "bumps" test | from baseline at 1, 2, and 3 hours after the study medication |
| Changes in performance in the psychophysical tests of cutaneous sensation (grating orientation task) | Parameters: grating orientation task | from baseline at 1, 2, and 3 hours after the study medication |
| Changes in performance in the psychophysical tests of cutaneous sensation (vibrotactile sensitivity) | Parameters: vibrotactile sensitivity | from baseline at 1, 2, and 3 hours after the study medication |
| Changes in performance in the psychophysical tests of cutaneous sensation (thermal sensitivity) | Parameters: thermal sensitivity | from baseline at 1, 2, and 3 hours after the study medication |
| Change in the rating on a 0-100 mm Visual Analogue Scale (VAS) of degree of sedation | from baseline at 1, 2, and 3 hours after the study medication |
| Change in the score of Symbol Digit Modalities Test (SDMT) | from baseline at 1, 2, and 3 hours after the study medication |
| Safety and tolerability of a single dose of AZD7325 by assessment of adverse events, vital signs, physical examination, ECG, and laboratory variables | Composite outcome measure | 3 times during the trial period, an expected average of 4 weeks (before each dose and 48-96 hours after the last dose of study medication). Adverse events also at follow-up telephone call within a week after the last dose of study medication |