Department of Clinical Neurophysiology
National Hospital for Neurology and Neurosurgery
Queen Square, London, WC1N 3BG
Tel: +44(0)20 344 84752 Fax: +44(0)20 7713 7743
Email: cnp@uclh.nhs.uk Web: www.ucl.ac.uk\cnp
Participant Information Sheet, Version 2, dated 23/09/2015
PART 1
Study title: Effects of AZD7325 on cutaneous sensation
Protocol reference number: 13/0261
Chief Investigator: Prof. Martin Koltzenburg
We would like to invite you to take part in a research study. Before you decide, it is important for you to
understand why the research is being done and what it would involve for you. Please take time to read the
following information carefully and discuss it with others if you wish.
Ask us if there is anything that is not clear. Take the time you need to decide whether or not you wish to
take part.
Part 1 tells you the purpose of the study and what will happen if you take part.
Part 2 gives you more detailed information about the conduct of the study
What is the purpose of this research?
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.
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We 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.
We 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).
Why have I been invited?
You are an adult man in good physical and mental health aged between 18 and 55 years and willing to
participate in the study which will include 12 participants.
Your safety during this study is a priority to us, therefore we will not be able to include you if:

Your body mass index (BMI = body weight (kg) / body height2 (m)) is lower than 18 or higher than 30
kg/m2;

You are allergic to any medication;

You have experienced seizures or unexplained loss of consciousness in the past;

You are not registered with a GP in the UK.
Do I have to take part?
Taking part in the research is entirely voluntary. It is up to you to decide whether to join the study or not.
We will describe the study and go through this information with you. If you agree to take part, we will give
you this information sheet to keep and then ask you to sign a consent form. You are free to withdraw at any
time without giving a reason.
What will happen to me if I take part?
If you decide to take part in the study, it will involve participation over approximately 3 weeks.
The research method of this study is a cross-over trial. In this type of trial each study participant will be
randomly assigned to one of two different treatments in which 2 capsules of study medication will be
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administered at each treatment (1 treatment consists of a placebo - a pill without any active medication, the
other treatments consist of study medications, each with a different strength). Between each period there
will be a break of at least 6.5 days so that the study medication is cleared from your body before you start
the new treatment period.
It is also a double-blinded trial. In this type of trial neither you nor your study physician will know which
treatment you will be given. However, if necessary, it is always possible to quickly find out which
treatment you are currently undergoing, by looking up a concealed code.
The timetable of the study is presented in the scheme below. On the first visit we will check your eligibility
for the study. If you meet the selection criteria, you will be invited to enrol in the study. In each of two
treatment periods you will be given two capsules. On that day you will be required to attend one test
session before and three test sessions (1, 2 and 3 hours) after the administration of the study medication. A
final safety check visit will be arranged 48-96 hours after the last treatment period and within a week of the
last treatment visit we will give you a call to finish your participation in this trial.
Visit 2
Visit 4
Visit 3
6.5 days
Treatment 2
1-21 days
Treatment 1
Screening
Not less than
48-96
hours
Final safety check
Visit 1
Within 7
days
from
Visit 4
Phone
call
Visit 1 (60-90 minutes). After you have given your consent we will:
 Ask you about your medical history and current medication.
 Perform a physical examination. This involves measuring your height and weight, body temperature,
blood pressure and heart rate.
 Record the electrical activity of your heart (ECG).
 Take your blood and urine samples to check your liver and kidney function. We will also take a Urine
Drug Screen test. This drug screen looks for substances such as recreational drugs notably cannabis
and ecstasy or prescription medication such as opiates, antidepressants and benzodiazepines. If this
test is positive, we will not include you in the study.
 Briefly describe the methods that will be used in the study.
 Perform the following set of tests in the following order:
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1.) Visual analogue scale for sedation (VAS Sedation) (1 minute). We will ask you to mark how sleepy
you feel on a 10-cm-long line.
2.) Symbol Digit Modalities Test (SDMT) (2 minutes). We will give you a pencil and paper and ask you
to pair numbers with geometric figures in 90 seconds to evaluate your attention and motor speed.
3.) Skin sensation tests (25 minutes)

‘Bumps’. We will ask you to explore the surface of a plastic square which contains a small
elevation (bump) like a sand corn in one of 5 areas (identified by a different colour) on an
otherwise even surface. The height of the bumps varies and we want to find out the smallest
height that you can detect.

Grating orientation task. We will use plastic disks with calibrated grooves. The investigator
will apply them gently to the skin either along or across the axis of your finger and we will
ask you to identify the direction. We repeat this 20 times for each disk to find out the disk
with the finest groove spacing that you can detect.

Vibration detection. Using a special device, we will apply brief vibrating stimuli of different
frequencies onto the pad of your finger and record the smallest difference in vibration
frequencies that you can detect.

Temperature detection. We will ask you to put your finger against a metal probe which slowly
changes the temperature. You will be asked to press a button as soon as you feel that the
probe becomes cold or warm or when the heat becomes painful. We will repeat this three
times at each spot to find the average temperature difference you can detect.
4.) Manual dexterity (30 minutes). We will use two methods to test your manual dexterity.

Object lifting task. We will ask you to use thumb and index finger to manipulate a metal
object. We will ask you (i) to press the object, (ii) to let it slip, (iii) to lift it approximately 2
cm above the table while we keep the weight constant or change it. We will be measuring
your grip force (GF) and lift force (LF).

Peg board test. We will assess your hand dexterity using the so called peg boards. You will
be asked to put metal pegs as quickly as possible into a row of holes on a board.
Subsequently, we will look through your data and test results. We will also contact your GP and ask for a
copy of your medical history. If you meet the criteria for enrolment in the study, we will contact you to
arrange the next visit and give you guidance on how to prepare for it.
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Visits 2 and 3. During these visits we will give you two pills that contain 10 mg of AZD7325 (total dose of
20 mg) or a placebo (pills without an active ingredient). The pills are deliberately made to look identical so
that neither you nor the investigator knows which treatment you receive. Over the study period, you will
receive one of each treatment in a random order.
We will perform the following assessment procedures at given times (see the table below).
Visit 2and 3
Visit 4
Assessment
Treatment
Final safety check
Physical examination
Before pill

Day 3
Inclusion/exclusion criteria
Before pill (Visit 2)
Blood and urine tests
Before pill

ECG
Before pill

Urine Drug Screen
Before pill
VAS of sedation
Before and 1, 2, 3 hours after pill
SDMT Test
Before and 1, 2, 3 hours after pill
Grip-lift task
Before and 1, 2, 3 hours after pill
Nine hole peg task
Before and 1, 2, 3 hours after pill
Skin sensation tests
Before and 1, 2, 3 hours after pill
Check for side effects


= collected throughout the day whenever necessary
We will schedule visits at the same time in the morning. On Visits 2 and 3, the tests will roughly take 5-6
hours in the morning. You will not have to stay in the hospital after the 3-hour assessments have been
completed. However, if at this point you experience any side effects that make it unsafe for you to leave the
hospital, we will ask you to stay so that we can observe you until you are fit to go home.
Visit 4. We will schedule a visit for final safety check-up 2 to 4 days after you have taken the last dose of
the study medication. This visit will last 30-60 minutes and we will give you a phone call afterwards
(within a week after the last treatment visit) to inform you about the test results and check for any side
effects you might have experienced. This will be considered as the end of your participation in the study.
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Expenses and payments
You will receive a financial compensation for your time and travel after the completion of scheduled study
assessments at the end of each visit:

Screening visit (Visit 1) – £20.

Treatment visits (Visits 2 and 3) – £90 per visit.

Safety check visit (Visit 4) - £30.
If you complete the study, you will receive £230 in total as reimbursement. If you withdraw from the
study, the total amount reimbursed will depend on how many visits you have completed (e.g., if you
withdraw after the first treatment visit, you will receive £110 in total (£20 for the screening visit, £90 for
completion of one treatment visit).
What will I have to do?
AZD7325 is a drug designed to act more selectively in the brain to avoid the sedative and addictive effects.
It has been studied in more than 700 people so far and proved to be generally well tolerated. This study is a
phase I clinical trial which means we will further explore the effects and safety of the drug in healthy
volunteers. It is designed to minimise any possible risks related to this drug, and for this, your cooperation
is essential.
If you decide to participate in the study, we will ask you to take certain measures for the duration of the
study and for a short time after the study. Your responsibilities are as follows:

Attend all scheduled visits. The visits will be arranged at the same time in the morning and we will
give you an individual timetable. You will not have to stay in hospital between the visits. If you are
unable to attend the scheduled visits we might have to exclude you from the study participation.

On the visit days, we will ask you to have a light low-fat breakfast of your choice before you arrive to
the hospital.
o Avoid grapefruit juice as it may alter the way the drug is processed in the liver.
o Do not consume alcohol 24 hours before and on the days of the scheduled visits, as it may interfere
with the action of the study drug and test results. It is very important that you do not have any alcohol
throughout the days when you take the study medication, even after all the assessments have been
completed. Alcohol may interact with AZD7325 in an unpredictable way; therefore allow at least 24
hours after taking the study pill before having a drink.
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
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Do not smoke. We will ask you to refrain from smoking or chewing tobacco 24 hours before and on
the days of the scheduled visits.

Avoid driving and operating machinery. AZD7325 may make you feel sleepy and affect your
concentration. Therefore we will ask you not to drive a motorised vehicle, bicycle or operate heavy
machinery for 48 hours after you have taken the pill. You can return home unaccompanied, but make
sure that you do not have to drive or cycle back on the treatment days. We will also advice you not to
take any important decisions 48 hours after the pill.

Other medication. Other drugs may interfere with the action of AZD7325 or the way it is cleared from
the body. Therefore it is important that you avoid using any prescription medication two weeks before
taking the first study pill and during the duration of the study. However, participation in the study
should not prevent you from receiving any appropriate treatment if necessary (e.g., delay the use
of antibiotics in case of pneumonia). On each visit, we will ask you about any other medication that
you were taking. Based on this information we might consider ending your participation in the study.

Contraception. AZD7325 did not cause damage to the genetic information within the cells in animal
studies and it is unlikely that a single dose of this drug can damage the human sperm and consequently
the foetus. However, as no such data in humans is available, we will ask you to avoid unprotected sex
and donating sperm during your participation in the study and until 1 week after taking the last pill of
the study drug. We will advise you on reliable contraception methods. If your partner gets pregnant
during your participation in the study, we expect you to inform us as soon as possible. We will then
ask for your partner’s consent to follow-up the pregnancy.

Participation in other clinical trials. Taking part in too many studies of new medicines can be harmful
for you. Therefore we will not include you in our study if you participated in another clinical trial
within the last month or more than four drug trials in the past 12 months.
Participation in other clinical trials which involve application of medicines during this study period
is not allowed.
The Over-volunteering Prevention System (TOPS). You must not take part in too many studies because
it may have an adverse effect on your wellbeing. To help research units, the Health Research Authority
keeps a database of healthy volunteers and when they take part in studies.
We shall enter some of your details into the database:

your National Insurance Number (if you're a UK citizen); or

your passport number and country of origin (if you're not a UK citizen); and
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the date of your last dose of study medicine
If you withdraw from the study before you receive any study medicine, the database will show that you
never received a dose.
Only staff working on this trial and other medicines research units can use the database. We may call other
units, or they may call us, to check your details. We'll keep your details for at least 2 years.
We may consider stopping your participation in the study if you are unable to adhere to these
restraints.
What are the possible disadvantages and risks of taking part?
Before participating you should consider if this will affect any insurance you have and seek advice if
necessary.
You may find participation in this study time consuming. It may cause you some inconvenience due to
restrictions on lifestyle (e.g., food and drink, driving, sex).
Blood samples will be taken during each visit, so there is a possibility of bruising or discomfort.
The tests that we will use to assess the motor control and skin sensation of your hand are non-invasive and
have no significant risks. You might find the testing of heat evoked pain slightly uncomfortable, but this
will last only very briefly and the temperature of the probe will quickly return to baseline as soon as you
press the button. The extreme temperatures of the probe and the duration of exposure to them are limited to
prevent any temperature-related skin injuries.
The risks of AZD7325
This drug has been so far studied in 722 people at single and repeated doses and was overall well tolerated.
The most common adverse effects observed after a single dose of the drug were related to its action in the
brain, i.e., dizziness, sleepiness, headache, euphoric mood or tingling sensation in the body. They were of
almost exclusively mild intensity and did not require stopping participation in the study.
We will observe you closely during the period of the study to make sure that any possible adverse effects
are detected and, if necessary, treated on time. For this, we will register any complaints that you might have
after taking the study pill and may check your blood pressure, heart rate and record ECG repeatedly. We
will also take your blood and urine samples for safety checks at the beginning of each visit.
There will be a 24-hour phone number to contact your investigating doctor, in case you feel unwell.
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What are the side effects of the treatment received when taking part?
This drug has been so far studied in 722 people at single and repeated doses and was overall well tolerated.
Single doses of AZD7325 ranging from 0.2 mg to 100 mg were tested in 147 healthy volunteers in 5
studies. The observed side effects after a single dose of the drug are listed below:

Very common side effects of AZD7325 were related to its action in the brain.
Dizziness, sleepiness, tingling sensation in the body, and euphoric mood were experienced by more
than 10 % of participants. In the vast majority of cases they occurred at the time when the drug
concentration in the blood reached its peak ( i.e., 1-2 hrs after the intake of the drug), but were almost
exclusively of mild intensity and did not require stopping participation in the study.

Less common side effects were headache, slowed thinking and gastrointestinal tract disturbances
such as dry mouth or nausea. Increased sweating, fatigue, muscle weakness, impaired balance,
attention or vision were reported by less than 1 in 100 participants.

Other side effects. This is a new drug and rare or extremely rare side effects might be yet unknown.

Interactions with other drugs. AZD7325 can potentially interfere with the action of other drugs that
are cleared from the body by liver. If AZD7325 is used with drugs or substances that are sedating
(like alcohol, benzodiazepines), it can potentially enhance these sedating effects in an unpredictable
way.
If you have to start taking any other medicine during your participation in the study, you should
inform your investigating doctor before the treatment with AZD7325 is started.

Risk to foetus. The data from studies in animals did not show any adverse effects on the development
of the embryos. However, no such data exists on humans. If your partner is pregnant, we will ask you
to use a condom during intercourse from the first pill of the study drug until 1 week after the last pill.
This is necessary to prevent any possibility of the drug being passed from the ejaculate to the woman
and then to the foetus.
What are the possible benefits of taking part?
Participation in the study will have no direct benefits to you, but you may find it a positive altruistic
experience to contribute to medical research. Information that we get from this study might help improve
the treatment of patients with certain neurological diseases such as polyneuropathy. Damage to peripheral
nerves in these conditions results in impaired sensation and manual dexterity and disturbs daily living tasks
of these patients (e.g., doing up buttons or holding a cup).
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What happens when the research study stops?
We will contact you by phone within a week from your last visit and this will be considered the end of your
participation in the study. However, if you experience any adverse effects at this or any other point of the
study, we will observe you till they are completely resolved.
What if there is a problem?
Any complaint about the way you have been dealt with during the clinical trial or any possible harm you
might suffer will be addressed. The detailed information concerning this is given in Part 2 of this
information sheet. If you have any concerns or complaints you should contact your study doctor in the first
instance.
Will my taking part in the study be kept confidential?
Yes. We will follow ethical and legal practice and all information about you will be handled in confidence.
The details are included in Part 2.
Contact Details
Your Doctor
Prof Martin Koltzenburg
Tel. Number: (020) 344 84752
Your Research Fellow
Dr Gintaute Samusyte
Tel. Number: (020) 344 83379
This completes Part 1 of the Information Sheet.
If the information in Part 1 has interested you and you are considering participation, please read the
additional information in Part 2 before making any decision.
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Part 2
What if relevant new information becomes available?
Sometimes we get new information about the treatment being studied. If this happens, we will tell you
about it and discuss whether you want to or should continue in the study. If you decide to continue in the
study we will ask you to sign an updated consent form.
What will happen if I don’t want to carry on with the study?
You can decide to stop participating in the study at any time. We will ask you about the reasons for your
decision, but you may also not give any. Any stored blood samples that can be identified as yours will be
destroyed if you wish.
If you decide to withdraw from the study after taking the drug, we will ask you to attend the scheduled
follow-up visit. This is necessary to ensure your safety. In case of any adverse events, we will ask you to
keep in contact with us to let us know your progress.
What if there is a problem?
Complaints
If you have a concern about any aspect of this study, you should ask to speak to the researchers who will do
their best to answer your questions [(020) 344 83379)]. If you remain unhappy and wish to complain
formally, you can do this with the National Hospital for Neurology and Neurosurgery, Patient Advise and
Liaison Service. Details can be obtained from 020 3448 3237.
Every care will be taken in the course of this clinical trial. However in the unlikely event that you are
injured by taking part, compensation may be available.
If you suspect that the injury is the result of the Sponsor’s (University College London) or the hospital's
negligence then you may be able to claim compensation. After discussing with your study doctor, please
make the claim in writing to the Prof Martin Koltzenburg who is the Chief Investigator for the clinical trial
and is based at the Department of Clinical Neurophysiology, at the National Hospital for Neurology and
Neurosurgery. The Chief Investigator will then pass the claim to the Sponsor’s Insurers, via the Sponsor’s
office. You may have to bear the costs of the legal action initially, and you should consult a lawyer about
this.
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Participants may also be able to claim compensation for injury caused by participation in this clinical trial
without the need to prove negligence on the part of University College London or another party. You
should discuss this possibility with your study doctor in the same way as above.
Regardless of this, if you wish to complain, or have any concerns about any aspect of the way you have
been approached or treated by members of staff or about any side effects (adverse events) you may have
experienced due to your participation in the clinical trial, the normal National Health Service complaints
mechanisms are available to you. Please ask your study doctor if you would like more information on this.
Details can also be obtained from the Department of Health website: http://www.dh.gov.uk.
Will my taking part in this study be kept confidential?
If you consent to take part in this study, the records obtained while you are in this study as well as related
health records will remain strictly confidential at all times. The information will be held securely on paper
and electronically at the hospital site managing this research (National Hospital for Neurology and
Neurosurgery) under the provisions of the 1998 Data Protection Act. Your name will not be passed to
anyone else outside the research team or the Sponsor (UCL), who is not involved in the trial. You will be
allocated a trial number, which will be used as a code to identify you on all trial forms. Any information
about you which leaves the hospital will have your name and address removed so that you cannot be
recognised.
Your records will be available to people authorised to work on the trial but may also need to be made
available to people authorised by the Sponsor, which is the organisation responsible for ensuring that the
study is carried out correctly. By signing the consent form you agree to this access for the current study
and any further research that may be conducted in relation to it, even if you withdraw from the current
study.
The information collected about you may also be shown to authorised people from the UK Regulatory
Authority (the Medicines and Healthcare Products Regulatory Authority); this is to ensure that the study is
carried out to the highest possible scientific standards. All will have a duty of confidentiality to you as a
research participant.
If you withdraw consent from further study, unless you object, your data and samples will remain on file
and will be included in the final study analysis.
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In line with the regulations, at the end of the study your data will be securely archived for a minimum of 20
years. Arrangements for confidential destruction will then be made.
Will my GP be informed of my involvement?
We will include you in this study only if you are in good health and do not require any other treatment. We
will also inform your GP of your participation in this clinical trial and ask for a summary of your medical
history. If the tests conducted during the study show abnormalities in your ECG, blood and urine test, we
will advise you if any further investigation and care is needed.
What will happen to any samples I give?
For this study, we will take your blood and urine samples. They will be collected, processed, and analyzed
at local hospital labs in accordance with routine hospital procedures. The results of these studies will be
anonymized and the sample destroyed.
Will any genetic tests be done?
No genetic tests will be done in this study.
What will happen to the results of the research study?
The results of the study will be available after it finishes and will usually be published in a medical journal
or be presented at a scientific conference. The data will be anonymous and none of the patients involved in
the trial will be identified in any report or publication.
Should you wish to see the results, or the publication, please ask your study doctor.
Who is organising and funding the research?
This research is funded by the Medical Research Council (MRC), via a research grant. Astra Zeneca, a
pharmaceutical company, is supporting the project by providing the study drug. University College London
(UCL) is acting as sponsor.
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Who has reviewed the study?
All research in the NHS is looked at by independent group of people, called a Research Ethics Committee,
to protect your interests. This study has been reviewed and given favourable opinion by the London –
West London & GTAC Research Ethics Committee (reference number: 15/LO/0814).
Further information and contact details
You are encouraged to ask any questions you wish, before, during or after your treatment. If you have any
questions about the study, please speak to your study doctor, who will be able to provide you with up to
date information about the drug/procedure(s) involved. If you wish to read the research on which this study
is based, please ask your study doctor. If you require any further information or have any concerns while
taking part in the study please contact one of the following people:
Your Doctor
Prof Martin Koltzenburg
Tel. Number: (020) 344 84752
Your Research Fellow
Dr Gintaute Samusyte
Tel. Number: (020) 344 83379
Emergency telephone numbers
If during the trial you need any urgent medical care you or a treating physician can call the following
numbers which will be available 24 hours a day: 07925 800934 or 07983 575738
If you decide you would like to take part then please read and sign the consent form. You will be given a
copy of this information sheet and the consent form to keep. A copy of the consent form will be filed in
your patient notes, one will be filed with the study records and one may be sent to the Research Sponsor.
You can have more time to think this over if you are at all unsure.
Thank you for taking the time to read this information sheet and to consider taking part in this study.