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Effects of GABA Modulator AZD7325 on Cutaneous Sensation

Information source: University College, London
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Healthy

Intervention: 2 mg AZD7325 (Drug); 10 mg AZD7325 (Drug); Placebo (Drug)

Phase: Phase 1

Status: Not yet recruiting

Sponsored by: University College, London

Official(s) and/or principal investigator(s):
Martin Koltzenburg, Prof, Principal Investigator, Affiliation: Institute of Neurology, University College London

Overall contact:
Martin Koltzenburg, Prof, Phone: 442034484752, Email: m.koltzenburg@ucl.ac.uk

Summary

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).

Clinical Details

Official title: A Phase I Single Site, Single Dose, Randomized, Double-blind, Placebo Controlled, 3-way Cross-over Biomarker Study Investigating the Effect of the GABA Modulator AZD7325 on Cutaneous Sensation in Healthy Volunteers

Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Primary outcome: Change in peak grip force in an object manipulation task

Secondary outcome:

Changes in parameters of object manipulation in a object manipulation task (grip force rate)

Changes in parameters of object manipulation in a object manipulation task (load force rate)

Changes in parameters of object manipulation in a object manipulation task (static load force)

Changes in parameters of object manipulation in a object manipulation task (static grip force)

Changes in parameters of object manipulation in a object manipulation task (9-hole pegboard test)

Changes in performance in the psychophysical tests of cutaneous sensation ("bumps" test)

Changes in performance in the psychophysical tests of cutaneous sensation (grating orientation task)

Changes in performance in the psychophysical tests of cutaneous sensation (vibrotactile sensitivity)

Changes in performance in the psychophysical tests of cutaneous sensation (thermal sensitivity)

Change in the rating on a 0-100 mm Visual Analogue Scale (VAS) of degree of sedation

Change in the score of Symbol Digit Modalities Test (SDMT)

Safety and tolerability of a single dose of AZD7325 by assessment of adverse events, vital signs, physical examination, ECG, and laboratory variables

Eligibility

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Male.

Criteria:

Inclusion Criteria:

- Male adults aged 18 to 55 years (extremes are included)

- A body weight resulting in a body mass index (BMI) of 18-30 kg/m2 (extremes included)

using the formula BMI = body-weight [in kg] / body-height [in m]2

- Able and willing to sign the Informed Consent Form prior to screening evaluations.

- History of good physical and mental health as determined by history taking and

laboratory examinations, ECG, blood pressure and heart rate recordings as judged by the investigator

- Willing not to consume alcohol or to smoke or chew tobacco on days of assessments

- Subjects must be willing to avoid unprotected vaginal intercourse with women of child

bearing potential (see above under 3. 5) or donating sperm for the duration of the study and a further 1 week after drug administration. Exclusion Criteria:

- History of allergy/idiosyncrasy to AZD7325 or chemically related compounds or

excipients which may be employed in the study or to any other drug used in the past

- Subject has taken systemically (po, iv) any potent or moderate CYP3A4 or CYP2C9

inhibitor, 1 month prior to screening (topical or inhaled are permitted) such as: aprepitant, barbiturates, carbamazepine, clarithromycin, erythromycin, cyclosporine, diltiazem, efavirenz, fluconazole, HIV protease inhibitors, glucocorticoids, itraconazole (oral/IV), ketoconazole, nefazodone, nevirapine, phenytoin, pioglitazone, primidone, rifabutin, rifampicin, telithromycin, St. John's wort, verapamil

- Use of any prescription drug judged by the investigator as potentially interfering

with this trial within two weeks prior to the first dosing, except for topical medication without systemic exposure

- Clinically relevant history or presence of any medical disorder, potentially

interfering with this trial

- Clinically relevant abnormal laboratory, ECG, HR or BP at screening as judged by the

investigator

- History of or current abuse of drugs (including prescription medication) or alcohol

or solvents

- Smoking in excess of 5 cigarettes per day or the equivalent within 28 days prior to

the screening visit

- Smoking or chewing of tobacco or consume of alcohol, 24 hours before and on the days

of assessment

- Subject is family member or in the employment line management of study personnel

- Subject has abnormal screening laboratory values

- Subject's partner is planning pregnancy within 3 months of last dosing

- Participation in an IMP intervention trial within last month or more than four in the

previous 12 months

- Abnormal responses in the object manipulation task and psychophysical measures, SDMT,

VAS outside 95% confidence interval of normal at screening visit

- Subjects with a history of epilepsy, seizures or episodes of unexplained and

unprovoked loss of consciousness

Locations and Contacts

Martin Koltzenburg, Prof, Phone: 442034484752, Email: m.koltzenburg@ucl.ac.uk

National Hospital for Neurology and Neurosurgery, London WC1N 3BG, United Kingdom; Not yet recruiting
Martin Koltzenburg, Prof, Phone: 442034484752, Email: m.koltzenburg@ucl.ac.uk
Gintaute Samusyte, MD, Phone: 4402034483379, Email: g.samusyte@ucl.ac.uk
Martin Koltzenburg, Prof, Principal Investigator
Gintaute Samusyte, MD, Sub-Investigator
Additional Information

Starting date: August 2015
Last updated: August 19, 2015

Page last updated: August 23, 2015

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