HealthyPhase 1NCT02530580
Effects of GABA Modulator AZD7325 on Cutaneous Sensation
A Phase 1 study testing 20 mg AZD7325 in people with Healthy, run by University College, London at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- 20 mg AZD7325
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Feb 2016to Jul 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
National Hospital for Neurology and Neurosurgery
London, WC1N 3BG
About this study
Official title: A Phase I Single Site, Single Dose, Randomized, Double-blind, Placebo Controlled, 2-way Cross-over Biomarker Study Investigating the Effect of the GABA Modulator AZD7325 on Cutaneous Sensation in Healthy Volunteers
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.
Read more
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).
- Conditions
- Healthy
- Being tested
- 20 mg AZD7325, Placebo
- Keywords
- GABA modulator, AZD7325, Object manipulation, Cutaneous sensation, Manual dexterity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
20 mg AZD7325Drug
A single 20 mg oral dose of AZD7325
PlaceboDrug
A single oral dose
| Study group | Role | What they receive |
|---|---|---|
| 20 mg AZD7325 | Experimental | 10 mg AZD7325 in orange capsule, Size 0, 2 capsules as a single oral dose Receives: Drug: 20 mg AZD7325; Drug: Placebo |
| Placebo | Placebo comparator | 10 mg Microcrystalline cellulose in orange capsule, Size 0, 2 capsules as a single oral dose Receives: Drug: 20 mg AZD7325; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in peak grip force in an object manipulation task
Measured: from baseline at 1, 2, and 3 hours after the study medication
Secondary outcomes (12)
Changes in parameters of object manipulation in a object manipulation task (grip force rate)
Parameters: grip force rate
Measured: 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)
Parameters: load force rate
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: from baseline at 1, 2, and 3 hours after the study medication
Change in the score of Symbol Digit Modalities Test (SDMT)
Measured: 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
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2015 (estimated)
- Study startFeb 2016
- Primary completionJul 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Martin Koltzenburg, Prof, Principal investigator, Institute of Neurology, University College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02530580
- Sponsor's protocol ID
- 13/0261
- Other IDs
- 2015-000642-35, 2015
- Status last verified
- Jul 2016
- First submitted
- 3 Aug 2015
- Last updated
- 27 Jul 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Single Site, Single Dose, Randomized, Double-blind, Placebo Controlled, 2-way Cross-over Biomarker Study Investigating the Effect of the GABA Modulator AZD7325 on Cutaneous Sensation in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT02530580
- Acronym / sponsor ID
- 13/0261
- Conditions
- Healthy
- Keywords
- GABA modulator, AZD7325, Object manipulation, Cutaneous sensation, Manual dexterity
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- Feb 2016
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 21 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 20 mg AZD7325 | Experimental | Drug: 20 mg AZD7325, Drug: Placebo10 mg AZD7325 in orange capsule, Size 0, 2 capsules as a single oral dose |
| Placebo | Placebo comparator | Drug: 20 mg AZD7325, Drug: Placebo10 mg Microcrystalline cellulose in orange capsule, Size 0, 2 capsules as a single oral dose |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 20 mg AZD7325A single 20 mg oral dose of AZD7325 | Drug | 20 mg AZD7325, Placebo |
| PlaceboA single oral dose | Drug | 20 mg AZD7325, Placebo |
Primary outcome
Change in peak grip force in an object manipulation task
Time frame: from baseline at 1, 2, and 3 hours after the study medication
12 secondary outcomes
Changes in parameters of object manipulation in a object manipulation task (grip force rate)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: from baseline at 1, 2, and 3 hours after the study medication
Changes in performance in the psychophysical tests of cutaneous sensation ("bumps" test)
Time frame: 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)
Time frame: from baseline at 1, 2, and 3 hours after the study medication
Changes in performance in the psychophysical tests of cutaneous sensation (vibrotactile sensitivity)
Time frame: from baseline at 1, 2, and 3 hours after the study medication
Changes in performance in the psychophysical tests of cutaneous sensation (thermal sensitivity)
Time frame: 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
Time frame: from baseline at 1, 2, and 3 hours after the study medication
Change in the score of Symbol Digit Modalities Test (SDMT)
Time frame: 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
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin Koltzenburg, Prof principal investigator
Institute of Neurology, University College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 20 mg AZD7325 in people with Healthy, run by University College, London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in peak grip force in an object manipulation task (time frame: from baseline at 1, 2, and 3 hours after the study medication). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2016.