An Investigation of the Effects of Dual Orexin Antagonism on Emotional Processing and Learning in Healthy Individuals
Phase: PHASE4
Conditions: Learning, Cognitive Functioning, Emotional Processing
Sponsor: University of Oxford

CENTRAL UNIVERSITY RESEARCH ETHICS 
COMMITTEE (CUREC) 
Ethics Application 
Application: An investigation of the effects of dual orexin antagonism on emotional processing 
and learning in healthy individuals 
ID: 582356 
 
Risk:  
High 
Submitted: 
21 Feb 2026, 00:30 
Submission Approved: 
27 Feb 2026, 13:50 
Decision: 
6 Mar 2026, 12:44 
Applicant: 
Daniela Almeida Borges 
Submitter: 
Principal Investigator: 
Daniela Almeida Borges 
Professor Catherine Harmer 
Org Unit: 
Department of Psychiatry 
Project Title: 
An investigation of the effects of dual orexin antagonism on emotional 
processing and learning in healthy individuals 
Project Duration: 
09 Sep 2025 – 08 Mar 2027 
Funder: 
WT 
Project Description: 
This project is exploring how a brain system called the orexin system affects 
human behaviour and brain activity, especially in ways that may help us better 
understand and treat mental health conditions like depression. 
 
Orexin is a chemical in the brain that’s best known for helping regulate sleep and 
wakefulness. But scientists have also found that it plays a role in other important 
functions, like stress, emotion, reward, motivation, and thinking. Problems with 
these functions are common in mental health disorders. 
 
Previous studies in animals suggest that turning down orexin activity might help 
reduce stress and make people less sensitive to negative emotions. However, it 
has been difficult to study orexin in people—until now—because we haven’t had 
the right tools. 
 
That’s changing thanks to a new medication called daridorexant, which was 
recently approved for treating insomnia. This drug blocks orexin across the brain 
and gives researchers a new way to study how orexin affects behaviour in 
humans. 
 
In this study, healthy volunteers will be randomly given either a single dose of 
daridorexant or a placebo (a dummy pill), without knowing which one they’ve 
received. Then, they’ll complete tasks that test how they process emotions, learn 
from rewards, and use thinking skills. 
 
By comparing the two groups, the study aims to shed light on how the orexin 
system works in the human brain. The results could help us understand how 
orexin contributes to emotional and cognitive problems seen in depression, 
anxiety, and bipolar disorder—and whether targeting this system could lead to 
new treatments. 
 
This study is part of a larger research program funded by the Wellcome Trust. 
The results will be shared in a student thesis and may also be published in 
scientific journals or presented at conferences. All data will be anonymised, and 
the study will follow ethical guidelines, including being officially preregistered 
before it begins. 
 
Student Project: 
Yes - Masters by Research  
Supervisor: 
Catherine Harmer 
 
 

SCOPE 
Is this research: 
Yes 
Not research: 
 
Human Participant Involvement: 
Yes 
Research does not involve participants, tissue or 
personal data: 
Researcher division: 
Other 
Taught student module: 
SSH Minimal Risk: 
Any secondary data: 
No 
Secondary data only: 
Anonymised secondary Data: 
External ethics review required: 
No 
Identify NHS staff involvement: 
No 
Biological samples: 
Yes 
Biological samples yes: 
ONLY samples taken as part of this research 
Drug or medicine: 
Yes 
Foodstuffs or supplements: 
No 
Medical device: 
No 
OxTREC Scope: 
No 
OxTREC minimal risk: 
No 
 
 
 

RESEARCH TEAM 
Principal Investigator: 
Professor Catherine Harmer 
Student Researchers: 
 
Student name  
Degree Programme 
Department/Institute 
Dr Daniela Almeida Borges 
Ms by Research in Psychiatry 
Department of Psychiatry 
Researchers and Training: 
Researcher 
title and 
name  
Depart./ Institute 
Name 
Role in research 
Research 
Integrity 
Course* 
Research 
Integrity 
Refresher* 
Supplementary 
Module 
Information 
Security 
Training 
Other (please 
specify) 
Dr Daniela 
Almeida 
Borges 
Department of 
Psychiatry - 
PERL 
Involved in all 
aspects of the study 
26/11/24 
N/A 
Research 
involving 
human 
participants 
(26/11/24) 
08/12/2025 
NIHR GCP 
(03/12/24) 
Human Tissue Act 
training (26/11/24) 
Dr Michael 
Colwell 
Department of 
Psychiatry - 
PERL 
Involved in all 
aspects of the study 
N/A 
30/11/24 
Research 
Involving 
Human 
Participants 
(30/11/24) 
01/12/2025 
Human Tissue Act 
training (MRC) - 
20/05/2025; 
Good Research 
Practice (MRC) - 
07/12/21 
Georgia 
Feltham 
Department of 
Psychiatry - 
PERL 
Research Assistant 
Overseeing day-to-
day management of 
project (including 
set-up, recruitment, 
data collection and 
analysis). 
10/01/24 
N/A 
Research 
involving 
human 
participants 
(19/01/24) 
24/04/2025 
Human Tissue Act 
training (12/01/24) 
Professor 
Simon Kyle 
Sir Jules Thorn 
Sleep and 
Circadian 
Neuroscience 
Institute 
Involved in study 
design, data 
interpretation and 
write up 
N/A 
March 
2025 
Research 
involving 
human 
participants 
(March 2025) 
March 2025 
Good Clinical 
Practice – 
January 2024 
Professor 
Catherine 
Harmer 
Department of 
Psychiatry - 
PERL 
Principal 
Investigator 
N/A 
30/07/2024 
Research 
involving 
human 
participants 
(30/07/2024) 
02/12/2025 
Good Clinical 
Practice – 
20/06/24 
External collaborator: 
No 
Medically qualified 
collaborator details: 
Name 
Medical Qualification 
Contact Details 
Institutional affiliation 
Professor 
Phil 
Cowen 
MD, FRCPsych, 
FMedSci 
phil.cowen@psych.ox.ac.uk 
+44 (0)1865 618311 
University of Oxford; Oxford Health 
NHS Foundation Trust 
Dr 
Daniela 
Borges 
MD (Univ. of Coimbra, 
Portugal), MRCPsych 
daniela.almeidaborges@ 
psych.ox.ac.uk 
Oxford University Hospitals NHS 
Foundation Trust; Oxford Health 
NHS Foundation Trust; 
Psychological Medicine, Kings 
College London 
 
 
Conflict of Interest: 
No 
 
 

METHODOLOGY 
Short title: 
Dual ORexin antagonism and Emotion and Affective processing (DOREA) study 
Research 
Summary: 
This experimental medicine study aims to understand the role of the orexin system in 
human behaviour and neural activity. The study utilises a double-blind, randomised, 
placebo-controlled, between-subjects trial design. The neuropsychological effects of 
single-dose daridorexant (50mg) versus placebo will be explored using a battery of tasks 
and questionnaires in healthy volunteers (18 to 40 years). The target sample size is 62 
participants, with 31 participants per allocation group (daridorexant and placebo). 
 
The primary outcomes of this study are: 
1. The Pavlovian reinforcement learning task (PALT) - choices, response time and 
computational parameters (derived from models fit to choice behaviour) 
2. The Emotional Go/No-Go task (EGNGT) - accuracy and response 
 
Secondary outcomes are : 
1) Pupillometry changes (pupil diameter) during a) the PALT and the b) the EGNGT. 
2) Salivary alpha-amylase (SAA) level changes 
3) Probabilistic Instrumental reinforcement learning task (PILT) - choices, response time 
and computational parameters (derived from models fit to choice behaviour) 
4) Change Detection task (CDT) - accuracy and response time 
5) Facial Expression Recognition Task (FERT) - Accuracy 
6) Emotional Classification Task (ECAT) - Accuracy 
7) Emotional Recall Task (EREC) - Accuracy 
 
The study involves three screening steps (a 15-minute online screening questionnaire, a 
45-minutes screening videocall and in-person eligibility checks at the start of the first study 
visit as described in the human participants section), two in-person study visits (lasting 2.5 
and 5 hours respectively) at the Department of Psychiatry and a 15-minute online follow-
up questionnaire the day after. 
 
During the study visit 1, participants will complete the baseline questionnaires - Consensus 
Sleep Diary for previous night (CSD), Morningness and Eveningness questionnaire 
reduced version (MEQr), Patient Health questionnaire (PHQ-9), State-Trait Anxiety 
Inventory (STAI), Perceived Deficits Questionnaire (PDQ), Positive and Negative Affect 
Schedule (PANAS), Visual analogue scale (VAS); the digit-span test (to assess baseline 
cognitive ability); and three of the computer tasks (PALT, EGNGT and CDT) to optimise 
the computational model validation and fit. 
 
Eligible participants will then be randomly assigned to treatment or placebo using the 
variance minimisation algorithm to ensure an even distribution of key covariates (gender 
and chronotype / MEQr score) between the groups. An independent researcher will 
generate the randomisation code following the procedure described by Sella, Raz, and 
Cohen Kadosh (2021), record the allocation on a Randomisation log, as well as identify 
and prepare the correct envelope with the drug or placebo by writing the participant ID on 
it. 
 
The study visit 2 will take place in the morning and within four weeks of study visit 1. 
Participants will be advised to avoid alcohol, recreational drugs, or grapefruit juice 24 hours 
before and after the study visit; as well as not to carry out activities requiring full alertness 
(e.g. driving) until the morning after drug administration. They will be asked to avoid 
smoking before the study visit, have a maximum of a cup of coffee (or equivalent) up to 90 

minutes before the visit time and have a light breakfast (e.g. 2 toasts of bread or yogurt 
with cereal). They will be advised to avoid attending the department by car or bicycle and 
will be provided with transport (if required) home after the study visit. 
 
In the study visit, eligibility is re-confirmed. If still eligible, participants will be asked to 
complete the CSD and a battery of questionnaires (PDQ, VAS, PANAS, STAI), which they 
will repeat after the administration of the drug. The Karolinska Sleepiness Scale will be 
completed just before drug administration and hourly until the end of the visit. 
 
Participants will then take a single tablet of daridorexant or placebo under supervision by a 
researcher. The following hour, they will be asked to remain within the Department of 
Psychiatry and avoid eating food, having non-caffeinated drinks or smoking until the end of 
the visit. 
 
After one hour, they will complete a series of computerised tasks with a researcher, which 
are expected to take about 3 hours. 
- The PALT involves predicting if a stimulus will lead to a tolerable electrical shock (via 
surface electrode attached to the back of the hand using adhesive strips); the level of pain 
is calibrated with the participant before the task takes place. During this task, participants 
will collect 3 saliva samples (before, during and 10 minutes after the task) using Salivette 
synthetic swabs to measure SAA levels (marker of sympathetic activity). 
- The PILT involves choosing between shapes which may result in monetary win or loss. 
Earnings from this task can be between £0-£10. 
- The emotional processing tasks (FERT, ECAT, EREC) involve correctly classifying 
emotional stimuli (i.e., words or faces) into their respective category (e.g., if a face shows 
an angry expression, pressing the 'Anger' button). 
- The EGNGT involves responding to an image which will either require one to inhibit a 
response ('no-go') or submit a response ('go'), while emotional distractors also appear on 
the screen (e.g., fearful face). 
- The CDT is a visuo-spatial working memory task where individuals will need to identify 
subtle changes of colour in an array of ‘items’ (e.g. coloured blocks) previously visualised. 
 
During the PALT and EGNGT, participants’ eye movements will be tracked alongside the 
degree of dilatation of their pupils using an eye-tracking equipment (EyeLink 1000 Plus). It 
is a safe and non-invasive way to measure by proxy the influence of neurochemicals (as 
noradrenaline) that interact with orexin while processing negative information (Sears, 
2013). 
 
Before the visit concludes, participants will be asked to repeat some questionnaires (as 
above). Participants will then be reminded of the safety advice, provided with the contact 
of the study medic for concerns over the next 24 hours, and organised transport home (if 
required). 
 
The day after, participants will be contacted via email asking them to complete a final online 
questionnaire on Qualtrics. This will include the CSD for the previous night, the side effects 
questionnaire and a question to guess if they took placebo or daridorexant. 
 
Lastly, participants will be asked for their bank details so they can be reimbursed for time 
and travel expenses by bank transfer. 
Location: 
Neurosciences Building, Department of Psychiatry, University of Oxford, Warneford 
Hospital, Warneford Lane, Oxford, OX3 7JX 

Location 
Permission: 
No 
CUREC 
Approved 
Procedure(s) 
yes: 
AP02 Studies involving administration of interviews and/or questionnaires on sensitive 
and/or medical topics, for testing and/or recruitment of participants 
AP18 Psychophysiological methods with adults 
AP19 Experimentally induced pain 
AP24 Taking urine, saliva, stool and/or venous blood samples 
CUREC Best 
Practice 
Guidance: 
International 
Risky Travel?: 
No 
Hazardous 
Substances: 
No 
Researcher 
Distress 
Potential?: 
No 
Lone Working?: 
No 
Non-public 
Visit?: 
No 
GMO Involved?: 
No 
Oversight: 
The study team will meet fortnightly to discuss the study, including potential adverse events 
and to check procedures are being followed (Approved Procedures and Best Practice 
Guidance). The Principal Investigator and named researchers will be present in these 
meetings. Student researchers will receive regular supervision/line management from the 
Principal Investigator. 
Research-
specific ethical 
considerations: 
1. Incidental findings 
Participants will be explicitly informed that their urine samples will be tested for pregnancy 
and recreational drug use, in both study visits, and informed of their right to withdraw from 
the study. They will also be told in advance that if the drug screen returns positive results, 
they will be excluded from the study. If participants consent to providing a urine sample for 
the pregnancy test and the test result is positive, the researcher will act in accordance with 
the pregnancy urine test SOP, wherein they will feed the result back to the medic covering 

the visit or a member of the research team, before communicating the result to the 
participant and providing any relevant advice. Results of the screening will remain 
confidential within the study team and participants will be informed of this. 
If a researcher has concerns that a volunteer may have an undiagnosed psychiatric 
condition that is causing distress (identified during the online screening videocall or 
following review of the mood-related questionnaires), CUREC Best practice guidance 08 
on Handling distress in participants will be followed. The researcher will seek advice from 
the Principal Investigator and /or study medic who may discuss the symptoms in greater 
detail with the volunteer and/or offer the opportunity to speak with a senior clinical 
researcher. If the volunteer indicates that they are not currently receiving support and it is 
felt necessary, they will be encouraged to contact their General Practitioner. 
 
2. Serious adverse events 
A serious adverse event (SAE) occurring to a participant should be reported to the Medical 
Sciences IDREC where, in the opinion of the Principal Investigator, the event was ‘related’ 
(resulted from administration of any of the research procedures) and ‘unexpected’ (the type 
of event is not listed in the protocol as an expected occurrence). Reports of related and 
unexpected SAEs should be submitted within 15 days of the Principal Investigator 
becoming aware of the event. For fatal and life-threatening SUSARs, this will be done no 
later than 7 calendar days after PI is first aware of the reaction. Any additional relevant 
information will be reported within 8 calendar days of the initial report. 
 
3. Data breach 
Potential data breaches will be reported immediately to the departmental Information 
Systems & Governance Officer and the university’s Information Compliance Team (ICT). 
The ICT will determine whether the data breach needs to be reported. 
 
4. Physical/verbal abuse and/or psychological distress from study participants 
There is a low risk of physical or verbal abuse from study participants. The study sample 
will be healthy young individuals without psychiatric conditions which is not typically 
considered a high risk sample. Screening (including psychiatric assessment) procedures 
will take place in a screening videocall and at the in-person study visits in the 
Neurosciences Building. In each instance, researchers will undertake assessments and 
data collection in a respectful, calm and compassionate manner. In the event that 
participants become distressed or physically/verbally abusive, researchers will not put 
themselves at unnecessary risk, per Best Practice Guidelines on researcher safety 
(BPG01) and participant psychological distress (BPG08). 
 
5. Complications of handling of biological specimen 
There is a risk of transmission of infectious disease or hazardous substances through the 
handling of urine and saliva samples. Researchers will be required to handle specimens 
during the participant screening process. Researchers will adhere to best practice/CUREC 
guidelines (AP024) during this process, including the donning of disposable aprons and 
gloves, handwashing before and after handling samples, and the safe and sterile disposal 
of samples, containers and drug tests using clinical waste systems. The collection of the 
samples will be completed by the participant. 
 
6. Safety incident 
In the unlikely event of a participant being involved in any safety incident at the Department 
of Psychiatry, their details (name) may be shared with safety officers, without any further 
personal information being shared. 

 
 
 

HUMAN PARTICIPANTS 
 
Participants 
Description: 
We are aiming to recruit 62 participants aged 18-40 years. Half (31 participants) will be 
randomly allocated to the daridorexant group and the other half (31 participants) to the 
placebo group. 
Sample size 
justification: 
A priori power calculations (80% power, 1 - β error probability) estimate a required sample 
of N = 58 (29 per group) for detecting group-level differences (two-tailed) in the primary 
outcomes (e.g., aversive learning behaviour) based on an expected standardised effect 
size/Cohen's d of 0.75 from previous experimental medicine work (Colwell et al., 2024). 
An additional four participants will be recruited to mitigate potential data quality or 
participant attrition issues from randomised participants, summating to a final required 
sample size of N=62. 
Participant 
Inclusion Criteria: 
- Adult participant, aged 18 to 40 years 
- Willing and able to give informed consent for participation in the trial 
- Able to follow study procedures as laid out in the participant information sheet 
- Able to read and understand English 
- Willing to avoid drinking alcohol, using recreational drugs, drinking grapefruit juice 24 
hours before and after the study visit 
- Willing to avoid driving or engaging in any activities requiring full alertness (e.g. cycling 
or operating heavy machinery) until the morning after the study visit day. 
- Able to complete computer tasks without eye glasses even if uses correction regularly 
Participant 
Exclusion 
Criteria: 
1. History of, receiving or seeking treatment for any sleep or circadian rhythm disorder or 
positive in screening questionnaires. 
2. History of, receiving or seeking treatment for any clinically significant mental health 
condition (including but not limited to schizophrenia, psychosis, bipolar affective disorder, 
major depressive disorder, obsessive compulsive disorder, post-traumatic stress disorder) 
or positive in screening questionnaires. 
3. History of, or current medical condition(s) which might increase the risk of oral 
administration of daridorexant, including: 
- ADHD requiring treatment with stimulants or other centrally-acting drugs 
- Neurological problems, including traumatic brain injury, epilepsy, Central Nervous 
System tumours or other severe neurological problems (e.g. Parkinson’s disease; 
blackouts requiring hospitalisation) 
- Current Asthma, Chronic Obstructive Pulmonary Disease,  emphysema or any medical 
condition that affects the lungs or breathing 
- Mild to severe hepatic impairment (Child-Pugh class A-C) 
- Severe renal disease 
- Severe gastrointestinal problems 
- History of, or current medical condition(s) which, in the opinion of the Investigator may 
interfere with the safety of the participant or the scientific integrity of the study 
4. Pregnancy (as determined by urine pregnancy test taken during first study visit), 
intention to become pregnant or breastfeeding during the study or over the following six 
months. 
5. Body mass index (BMI) below 18 or above 30kg/m2. 
6. Current or past history of drug or alcohol dependency. 
7. Regular alcohol consumption of more than 21 units per week or use of recreational 
drugs or performance-enhancing drugs (e.g. cannabis, cocaine, amphetamines) within 
past three months. 
8. Excessive caffeine consumption, i.e., consumption higher than 400mg a day of caffeine. 
This corresponds to more than 4 cups of brewed coffee, 6 espressos or filtered coffees, 9 
cups of black tea, 10 cans of cola, or two "energy shot" drinks. 

9. Smoking more than 5 cigarettes per day (or other nicotine replacement equivalent, 
including vaping on average more than 50 puffs a day). 
10. Current or recent (past two months) use of any medication or medical devices (e.g. 
implanted neurostimulator) that affect brain function for the exception of contraceptives 
(pill, the Depo-Provera injection or the progesterone implant). This includes drugs that 
cause sedation (e.g. benzodiazepines, opioids, tricyclic antidepressants or sedative 
antipsychotics) or antihistamines. 
11. Current use of any medications at risk of interaction with daridorexant; in particular: 
- strong or moderate CYP3A inhibitors (e.g. strong inhibitors - itraconazole, clarithromycin, 
ritonavir, grapefruit juice; moderate inhibitors - fluconazole, verapamil, diltiazem, 
erythromycin, ciprofloxacin, cyclosporine) 
- strong or moderate CYP3A inducers (e.g. of strong inducers - rifampicin, carbamazepine, 
St. John’s wort; moderate inducers -  bosentan, efavirenz, etravirine, modafinil) 
- Gastric pH-modifiers (e.g. famotidine and proton pump inhibitors such as omeprazole) 
- P-gp transporters (e.g. dabigatran, digoxin) 
12. Inability to ingest up to 95mg of lactose. 
13. Previous participation in any other drug study or sleep intervention study in the last 
three months. 
14. Previous participation in any other study by the Psychopharmacology and Emotion 
Research lab (Department of Psychiatry, University of Oxford) or which uses the same 
computer tasks in the last 6 months 
15. Participant is unlikely to comply with the clinical study protocol or is unsuitable for any 
other reason, in the opinion of the Investigator. 
Participant 
Protected 
Characteristics: 
In this study we will select participants of a certain age group (18 to 40 years) to minimise 
the variation of outcome results that could be influenced by having a mixture of different 
ages in the sample population. We have excluded from participation people with current 
or past diagnosis of mental illness (which can in some cases be considered a disability 
under the Equality Act 2010) to minimise initially the risk of using psychoactive drugs in 
clinical populations for an experimental medicine study design. 
Furthermore, pregnancy is an exclusion criterion as daridorexant is contraindicated in 
pregnancy. 
Participant 
Identification: 
Potential participants will be identified only through community advertisements (see below 
approaching participants section) and be given a link / QR code on our recruitment 
materials which will take them to the study online screening questionnaire where more 
information will be available. 
Vulnerable 
Participants: 
No 
Approaching 
participants 
Participants will be recruited by word of mouth, emails to departmental and college mailing 
lists (sent by the list holder on request of the researchers), posters in University and 
community spaces, local magazines, social media posts (Instagram, X, TikTok, Bluesky), 
NIHR Be Part of Research Volunteer Service registry (more information below), as well 
as through websites (e.g. Daily Info, Call for Participants, and MQ research website).  
The adverts (available in documents) will contain brief information about the inclusion 
criteria for the study and participant involvement, as well as contact details for the study 
email and link/ QR code to the study online screening questionnaire. We have also 
prepared Reels for social media promotion. All promotion text templates are included in a 
document attached. 
Participants may also be recruited via advertisements targeting Oxford Brookes 
University, following approval from Oxford Brookes Research Ethics Committee. Oxford 
Brookes will be made aware that the study drug is not licensed in the UK as part of this 
approval process. Any advertisements for Oxford Brookes students and staff will contain 

this additional statement: “Oxford Brookes University has knowledge of this study and has 
permitted recruitment at the University. In the event of any questions about the study, 
please contact the researchers in the first instance. Should you need to contact anyone 
at Oxford Brookes about this further, please email: ethics@brookes.ac.uk”. 
We will also contact other adult learning organisations (universities and colleges) to 
request their authorisation and cooperation to send email promotion or display posters 
about the study. This might require sharing of approved texts, study methodology and 
ethic submission documents and favourable opinion letters for review by the organisation 
ethics committee. 
 
We have agreed an email template (attached in documents) with the Be Part of Research 
Volunteer Service (BPORVS) team to be sent to registered study volunteers criteria. We 
will provide monthly updates to the team about the number of people that have registered 
to take part in the study through this service. No participant details will be shared. The 
purpose of the BPORVS is to allow members of the public to become volunteers by 
creating an account, specifying the areas of research that they are interested in and give 
consent to be contacted by the Be Part of Research team. Those who consent will receive 
information about BPORVS, in particular to alert them to specific BPORVS registered 
studies that they may be interested in, based on their volunteered details and study 
specific eligibility criteria, using an online self-registration service. The register is open to 
those that live in the UK, are over 18 and have an email address. At the time of registration, 
volunteers are made aware that they are not signing up to take part in a specific health 
study when they join this register and that they will only be signposted to studies that have 
NIHR funding or are listed on the NIHR RDN Portfolio. If the volunteer is interested in the 
study there will be a link in the email to take them to the study team (e.g. website, pre-
screener) where they will move into the study team’s screening process and consenting 
process if they take part in the study. The Be Part of Research Volunteer Service is funded 
by the Department of Health and Social Care and delivered by the National Institute for 
Health and Care Research (NIHR) in conjunction with Public Health Agency, Research & 
Development, Northern Ireland, NHS Scotland and Health and Care Research Wales. 
Further information on the Be Part of Research Volunteer Service is available here: 
https://bepartofresearch.nihr.ac.uk/volunteer-service/researchers 
Investigator 
Influence or 
Authority: 
No 
Participant 
Investigator 
Relationship: 
N/A 
Participant 
Recruit 
Information: 
1. Potential participants will be identified through community advertisements (see above 
approaching participants section) and be given a link / QR code on our recruitment 
materials which will take them to our study online screening questionnaire where the 
Participant Information Sheet (PIS; available in documents) will be available. Prospective 
participants can contact the named researchers via the study email for further information 
at any point. 
 
2. Then, prospective participants will be asked to complete the online screening 
questionnaire (on Qualtrics; available copy in documents) . They will firstly be presented 
with a link to the PIS and a copy of the study summary advert. Then, interested participants 
will be asked to tick a box to confirm they consent to complete the screening questionnaire 
to check if they meet the inclusion and exclusion criteria for the study. 

If they meet the eligibility criteria and are interested to take part in the study, participants 
will be asked to provide an email address. At this point, a screening ID number will be 
assigned to the participant. If researchers notice that one of the participants responses to 
the questionnaire might indicate they would not be eligible for the study, they will contact 
the participant via email to inform them of this. 
Otherwise, the contact details will not be asked, they will be thanked for their interest, 
signposted to the Department of Psychiatry (https://www.psych.ox.ac.uk/getinvolved) and 
Psychopharmacology and Emotion Research Laboratory (https://perloxford.com/) current 
studies webpages. There will be no further contact from the research team. 
 
3. If eligible after filling in the online screening questionnaire, participants will be contacted 
via email within 10 days to arrange a 45-minutes videocall screening session on MS 
Teams. We will offer screening session slots using the Bookings app of the University 
Nexus 365 for business account, which will collect their name and email address for the 
booking. Participants can also request to complete the session over telephone call. 
 
At the beginning of this online screening videocall, one of the named researchers will 
explain the study to the participant, confirm they read the PIS, and answer any questions 
that they might have. The researcher will then ask the participant to complete an online 
informed consent form on Qualtrics (available in documents). The participant must 
personally sign by typing their name and date the form before any study specific 
procedures are performed. The signatures of the researcher who presented and obtained 
the Informed Consent will be on the form. A copy of the completed online Informed 
Consent (in pdf) will be sent to the participant via email and another copy will be saved in 
the electronic TMF. 
 
The online screening videocall will then include the following screening procedures (case 
record form available in documents): 
- Personal contact details collection (separately recorded) 
- Demographic data including ethnicity, gender, age, years in full-time education 
- Medical history screening and details of current and past medication (including 
confirmation of exclusion criteria) 
- Selected sections of the Structured Clinical Interview for DSM-5 (SCID-5), which probes 
for past or current psychiatric illness (exclusion criteria) 
- Relevant screening questions for insomnia disorder (screen negative for insomnia 
symptoms on the Sleep Condition Indicator) and other sleep or circadian rhythm disorders 
(based on screening questions for other disorders identified by Wilson et al) 
 
If the participant does not meet the eligibility criteria for the study, the researcher will 
sensitively inform the participant they are ineligible and the screening process will end. If 
there are any questions about the participant’s suitability to take part in the study, the 
researcher will ask a study medic after the online screening videocall to check the 
information collected. The medical doctor might need to discuss the study with the 
participant and perform a medical examination, if deemed necessary. Participants will be 
informed of this and that they will be contacted with an outcome. If the outcome of the 
online screening videocall indicates that the participant meets all of the study eligibility 
criteria, the participant will be invited to the in-person first study visit and the date and time 
for this will be booked during the call. 
 
4. The study visit 1 at the Neurosciences building (Department of Psychiatry, Warneford 
Hospital) is expected to last 2.5 hours. It will start with checking if the participant has any 

questions about the study. Then the researcher will take a written consent from the 
participant using the latest approved version of the Informed Consent form in an iPad 
document or in paper (available in documents). The participant must personally sign and 
date the form, as well as the researcher who presented and obtained the Informed 
Consent. A copy of the completed Informed Consent form will be given to the participant 
either in paper or via email in PDF format. Another copy will be saved in the electronic 
TMF or on the TMF paper folder. This will then be followed by the final eligibility checks: 
- Review if any new medical problems or medications; 
- Weight and height measurement, for calculation of Body Mass Index (BMI) 
- Blood pressure and pulse recording at rest 
- Urine drug screening test for amphetamine, barbiturates, benzodiazepines, 
buprenorphine, 
cocaine, 
marijuana, 
methadone, 
methamphetamine, 
methylenedioxymethamphetamine 
(MDMA), 
morphine, 
methaqualone, 
opiates, 
phencyclidine, propoxyphene, tricyclic antidepressants, tramadol, ketamine, oxycodone, 
cotinine, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), fentanyl, synthetic 
marijuana, 6-mono-acetyl-morphine (6-MAM). 
- Urine pregnancy test (for female at birth) 
 
If the outcomes of the eligibility checks indicate: 
a) the participant meets all of the study eligibility criteria, the participant will be enrolled in 
the study and assigned a participant ID number. They will be asked to complete a battery 
of baseline questionnaires, the digit-span test and three of the computer tasks (as 
described in research methodology section) at this visit. 
b) the participant does not meet the eligibility criteria for the study, the researcher will 
sensitively inform the participant they are ineligible and the screening process will end. 
c) any questions about the participant’s suitability to take part in the study, the participant 
will still complete the baseline questionnaires and tasks. The researcher will ask a study 
medic during or after the study visit to check the information collected. The medical doctor 
might need to discuss the study with the participant and perform a medical examination, 
if deemed necessary. Participants will be informed of this and that they will be contacted 
with an outcome, if this is not completed at the visit. 
 
If during recruitment or screening procedures, a participant considers to take part in 
another research study that would meet the exclusion criteria for the DOREA study (any 
other drug study or sleep intervention study; any other study which uses the same 
computer tasks), they will be asked to make a decision independently about which study 
to participate in. 
Participant 
Decision 
Duration: 
The participant will be allowed as much time as wished to consider the information, and 
the opportunity to question the Investigator, their GP or other independent parties to 
decide whether they will participate in the study. This is only conditioned by the end of 
study which is the date of the last visit of the last participant. Written informed consent will 
then be obtained as described in the next question. 
Participants 
Informed 
Consent: 
Yes 
Participants 
Informed Consent 
More Info: 
Prospective participants will be able to access the latest version of the Participant 
Information Sheet (PIS) by selecting the link provided on all study adverts that will direct 
them to the study website, or receiving a copy through email after request. 
 
Prospective participants will be asked to complete the online screening questionnaire 
through a link available on the study website (as above) and will firstly be presented with 

a link to the PIS. Then, interested participants will be asked to tick a box to confirm their 
consent to complete the screening questionnaire to check if they meet the inclusion and 
exclusion criteria for the study. If the prospective participant is eligible and interested to 
take part in the study, they will be asked to share their contact details and will be be invited 
to book a videocall screening session within 10 days. 
 
Following this, at the online screening videocall, one of the named researchers will explain 
the study to the participant, confirm they read the PIS, and answer any questions that they 
might have about the study. Written and verbal versions of the PIS and Informed Consent 
form will be presented to the participants. This will detail the exact practical demands of 
the research, written from the participant’s perspective and in simple lay language. It will 
describe when and where they will be required to attend, what procedures are involved 
and for how long, how data will be collected and offer brief justification of the intervention. 
It will also contain information about any possible risks and benefits of taking part in the 
research, such as side effects of the study drug. Prospective participants will be allowed 
as much time as they wish to consider the information and will have the opportunity to ask 
questions of the Investigator/research team or other independent parties. It will be clearly 
stated that the participant is free to withdraw from the research until a month after their 
second study visit for any reason and with no obligation to give the reason for withdrawal. 
 
The researcher will then take written consent from the participant using the latest 
approved version of the Online Informed Consent form (available in documents) on 
Qualtrics. The researcher who obtained the consent will be suitable trained and 
experienced, and have been authorised to do so by the Principal Investigator. The 
participant must sign the form by typing their name and date the form before any study 
specific procedures are performed. The signatures of the researcher who presented and 
obtained the Informed Consent will be on the form. A copy of the signed consent form (in 
pdf) will be sent to the participant via email and another copy will be saved in the electronic 
TMF. 
 
At the start of first study visit (1) at the Neurosciences building (Department of Psychiatry, 
Warneford Hospital), the researcher will again take a written consent from the participant 
using the latest approved version of the Informed Consent form in an iPad (using a pdf 
version of the document) or in paper (available in documents). The participant must 
personally sign and date the form, as well as the researcher who presented and obtained 
the Informed Consent. A copy of the completed Informed Consent will be provided to the 
participant either in paper or via email in PDF format. Another copy will be retained in the 
electronic TMF or at the study site in the paper TMF folder. 
Any feedback: 
Yes 
Participant 
Feedback: 
Participants will be debriefed and have an opportunity to ask questions more 
detailed/complete descriptions about the study procedure/purpose after all data has been 
collected. Participants (and researchers) will not be aware of group allocation given the 
double-blind design, therefore this will not be included in the debriefing process. 
Withdrawal 
Arrangements: 
Each participant has the right to withdraw from the study at any time. Participants can also 
request for their data to be withdrawn until a month after their second in-person study visit. 
They will have to communicate this in writing to the study email. 
 
In addition, the Investigator may discontinue a participant from the research at any time if 
the Investigator considers it necessary for any reason including: 
•Pregnancy 

•Ineligibility (either arising during the research or retrospectively having been overlooked 
at screening) 
•Significant protocol deviation 
•Significant non-compliance with treatment regimen or research requirements 
•Withdrawal of Consent 
•Loss to follow up 
 
If a participant withdraws/is withdrawn from the study no further procedures or 
observations will continue to be required. 
In the case of withdrawal from the study prior to randomisation, all the participant data will 
be securely removed and not analysed. However, if the participant has been randomised 
and has received the study drug/placebo, their data from the tasks may be analysed if 
they withdraw one month after their second in-person study visit. Withdrawn participants 
will be replaced. The reason for withdrawal if given will be recorded in the Participant Log 
of the Trial Master File. 
Withdrawal More 
Information: 
Each participant has the right to withdraw from the study at any time for any reason without 
prejudice to future care, and with no obligation to give the reason for withdrawal. 
 
If a participant withdraws from the study prior to randomisation, all their data (personal, 
screening and research data) will be securely removed and not analysed, only keeping 
the screening ID, consent form, and reason for withdrawal if provided. In the case of an 
exclusion due to a positive drug test, this will be linked only with a screening ID number 
and all personal identifiers and information will be destroyed. 
 
If the participant has been randomised and has received the study drug/placebo, their 
data from the tasks may be analysed if they withdraw one month after their second in-
person study visit. Otherwise, we will remove their data and it will not be analysed. 
 
Participants will still be reimbursed pro-rata from the start of attending the first study visit 
to the point they participated in. 
 
In the case of a withdrawal, the type of withdrawal and reason for withdrawal will be 
recorded in the Participant log. 
 
Any participants that drop out without completing the study will be replaced. 
Participant 
Deception: 
No 
CUREC Approved 
Procedure 07: 
No 
Social Media: 
No 
Sensitive Topics: 
Yes 
Sensitive Topics 
More Info: 
In the screening procedures, we will enquire about participants medical and psychiatric 
history (please find in the supporting documents copies of the online screening 
questionnaire, the online screening videocall interview and first study visit eligibility 
checks). In the screening visit, participants will also undertake a standardised psychiatric 
interview (SCID-5) which enquires about an individual’s current and past psychological 
wellbeing (including questions about past traumatic experiences, substance abuse etc.). 
This might be uncomfortable for participants or reveal current psychological distress. This 
information is required to ensure that participants do not fulfil exclusion criteria including 
current or past psychiatric disorder, sleep disorders and some medical conditions. 
Illegal Behaviour: 
No 

Awareness 
Disclosure Harm: 
Yes 
Awareness 
Disclosure Harm 
More Info: 
In the screening procedures, participants will undertake a standardised psychiatric 
interview (SCID-5) in which participants will be asked directly by researchers about 
suicidal ideation. During the interview, they might also have questions that indirectly 
prompt for disclosure of current or past experiences of harm to themselves and others, 
abuse or neglect. To mitigate the risk associated with psychiatric interviewing, participants 
will be informed about the nature of the interview before their participation in the screening. 
 
All researchers involved in participant facing work will be provided training on the delivery 
of psychiatric interviews and required to read the best practice guidelines on researcher 
safety (BPG 01) and on handling distress in participants (BPG 08); as well as CUREC 
approved procedure on studies involving administration of interviews and/or 
questionnaires on sensitive and/or medical topics, for testing and/or recruitment of 
participants. Screening procedures (including psychiatric assessment) will take place in a 
screening videocall and at the in-person study visits in the Neurosciences Building.. 
 
Should there be a participant disclosure of a past or current intent to harm themselves or 
another, abuse or neglect, CUREC Best practice guidance on handling distress in 
participants (BPG 08) will be followed. The researcher will seek advice from the Principal 
Investigator and /or qualified medical doctor covering the visit who may discuss the 
symptoms in greater detail with the participant and/or offer the opportunity to speak with 
a senior clinical researcher. If the participant, indicates that they are not currently receiving 
support and it is felt necessary, they will be encouraged to contact their General 
Practitioner. In urgent situations, in which participants express thoughts of harming 
themselves imminently, they will be strongly advised to attend the local emergency 
department. 
 
The information collected about the participant during the course of the research is kept 
confidential. In the context of the above disclosures, confidentiality would only be 
breached in the very rare circumstance that is judged that the participant or someone else 
is at immediate risk of serious harm. In these circumstances, only information necessary 
to ensure immediate safety would be released and this would be discussed with the 
Principal Investigator and /or qualified medical doctor covering the visit. The only other 
circumstance in which information would be released is if it was requested by an order of 
a court of law. 
Risk of Injury: 
Yes 
Risk of Injury 
More Information: 
- Risk of psychological distress: As part of their eligibility screening, participants will 
undertake a standardised psychiatric interview (SCID-5) in order to ensure that they do 
not fulfil criteria for any current or past psychiatric disorder. Psychiatric interview questions 
enquire about an individual’s current and past psychological wellbeing (including 
questions about past traumatic experiences, substance abuse etc.). This might be 
uncomfortable for participants or reveal current psychological distress. There is a lower 
likelihood of this happening as prospective participants will be asked directly in the online 
screening questionnaire if they have been previously diagnosed with any significant  
mental health conditions as this would be an exclusion criteria for this study. 
 
- Risk of incidental findings: There is a risk of incidental findings being identified when 
doing the urine drug screen, the urine pregnancy test or identifying some signs/symptoms 
of an undiagnosed psychiatric condition that is causing distress to the participant. 
 

- Risk of side effects: side effects and adverse reactions to daridorexant administration 
have been described in drugs/substance section. 
 
- Risk of pain inducing task: One of the experimental behaviour tasks will involve the use 
of experimentally induced pain (individually tailored electrical stimulation) which have 
been used in previous studies (Browning 2015; Lawson 2014). It will be delivered via a 
surface electrode attached to the back of the non-dominant hand using adhesive strips 
following an established protocol (Approved Procedure 19). Beyond the risk of pain, the 
electrical pain stimuli by electrode may lead to a skin reaction which should clear within 2 
hours of completing the task. 
 
- Risk of using an eye-tracking and pupillometry device: Eye-tracking and pupillometry are 
non-invasive methods that pose no direct health risks to participants. In this study, an 
Eyelink 1000Plus (manufactured by SR Technologies) will be used to continuously 
measure pupil diameter and pupillary response dynamics under controlled lighting 
conditions. Participants will complete cognitive tasks on a specialized screen while resting 
their chin on a headrest, allowing the eye tracker to collect physiological data in a non-
invasive manner. The collected data will include pupil diameter (mm), pupil constriction 
velocity (mm/s), minimum diameter (mm), time to minimum diameter (s), relaxation 
velocity (mm/s), and final diameter (mm) (Connelly et al., 2014). Although most 
participants typically experience no discomfort during pupillometry studies, remaining in a 
fixed position (up to 20 minutes at a time) could feel uncomfortable for some. Eye-tracking 
records saccadic eye movements through Reflective Differencing of Infra-Red (IR) light 
emitted by IR emitters mounted on the Head Mounted Transducer. Prolonged exposure 
to IR light can pose a small risk of triggering seizures in individuals with photosensitive 
epilepsy (3–5% of people with epilepsy). 
Risk of Injury 
Mitigation: 
- Risk of psychological distress: To mitigate the risk associated with psychiatric 
interviewing, participants will be informed about the nature of the interview before their 
participation in the screening. 
- Risk of incidental findings: These will be addressed as described in the methodology 
section. 
 
- Risk of side effects: In order to minimise the risks, all participants will be screened for 
physical or psychological risk factors before enrolment in the study. In addition, a qualified 
medical doctor will always be available for phone advice and within 30 minutes of the 
Neurosciences building during the study procedures involving drug administration and all 
participants will receive detailed instructions on how to behave within 24h of intervention 
(e.g. avoid grapefruit juice, drugs, alcohol, sedative medication , driving, cycling, or 
operating heavy machinery) and what to do if they experience any problems following their 
participation. All participants will be provided with contact details of a research team 
member whom they can contact. 
 
- Risk of pain inducing task: There will be a calibration process prior to the experiment to 
guarantee that the current is well within the personally tolerable range of what the 
participants report as painful. In the calibration, the participant will be seated in a 
comfortable position and we will gradually turn up the magnitude of the current while 
explaining to the participant what to expect (i.e. painful stimulation). We will try to confirm 
the pain sensitivity threshold for the participant with small increments in the current. The 
subjective pain will be assessed by a 10-point scale on which 1 was defined as “minimal 
pain”, 10 as “worst possible pain”. The highest magnitude stimuli in the experiment will be 
equated to 8 on this scale. 

 
- Risk of using an eye-tracking and pupillometry device: Discomfort during the pupillometry 
study will be mitigated by providing supportive padding and ensuring a comfortable 
position. Participants will also be able to take breaks between blocks of cognitive tasks 
and may withdraw from the study at any time if they wish. To minimize the risk of seizure 
due to prolonged exposure of infra-red light, individuals with a history or diagnosis of 
epilepsy are excluded from the study. In the rare event that participants experience 
sensations or auras that may signal an impending seizure, they will be advised to avert 
their gaze from the eye tracker and should stop the task. 
Invasive 
Procedures: 
No 
DBS Check: 
Yes 
Participant 
Compensation: 
Yes 
Compensation 
Details: 
Participants will be paid by bank transfer up to £135 for full participation in the whole study. 
This is based on a rate of £15 per hour and with an expected 9-hour involvement in study 
activities. Additionally, participants can win up to an extra £10 depending on their 
performance in the cognitive tasks administered during the study visit. 
We will reimburse participants with a pro-rata amount if they withdraw before completing 
the whole study. 
If a participant attends the videocall screening session but is deemed ineligible to take 
part in the study, we will reimburse them with a pro-rata amount of £10. 
If a participant physically comes in to the first study visit but is deemed ineligible to take 
part in the study in the initial eligibility checks, we will reimburse them with a pro-rata 
amount of £15. 
If an eligible participant drops out after completing the baseline research activities in the 
first study visit, after daridorexant or placebo administration or has to be excluded before 
completing all research activities, they will be given a pro-rata amount to recompense the 
time they spent in the study based on £15 per hour rate and not exceeding the £135 . 
Reasonable travel expenses (up to £20 per visit; more if previously agreed) for any visits 
will be re-imbursed on production of receipts, or a mileage allowance provided as 
appropriate. On the second study visit, after drug administration, we will organise a taxi 
and/or public transport from the Warneford Hospital to the local accommodation, unless 
the participant has an equivalent transport arrangement (e.g. someone to drive them by 
car) already organised. 
Undue 
Incentives: 
No 
Compensation 
After Withdrawal: 
If participants do not complete the study, they will be given a pro-rata amount to 
recompense the time they did spend in the study as described above. 
 
 
 

SECURITY 
 
Security More Information: 
N/A 
Security Risk Mitigation: 
N/A 
Prevent duty: 
No 
 
ENVIRONMENTAL IMPACT 
Environmental Impact: 
The research project will not produce waste that will outright impact local ecology, 
hydrology, and the community. This study will require the use of printed materials 
and  computer equipment which may produce some minor impact to the 
environment. There is also the impact of participant transport, particularly the 
necessity of a taxi or car drive home after the study visit. Motor vehicles have a 
significant environmental impact on air pollution (from exhaust emissions), 
greenhouse gas emissions, increased traffic congestion, resource consumption 
and noise pollution. We will try to minimise the environmental impact of the study 
by implementing some preventative measures (as described below). 
Environmental Impact 
Monitored: 
To minimise the environmental impact of our study, we will: 
 
1) Print materials only when necessary; questionnaires and most data collection 
will be collected using digital equipment to avoid paper waste, and we will have 
an electronic trial master file. 
 
2) Encourage participants to use less polluting means of transportation (as 
cycling, walking or use public transport) for visits, with the exception of the journey 
home from the study visit; this is due to the risk of side effects after daridorexant 
administration and the safety measure of the participant being driven home. 
 
3) Testing equipment throughout the study will be powered off when not in 
operation and include a charging limit. Lights in study testing rooms will be 
switched off when not in use. 
 
4) We will be mindful how long experimental tasks last (e.g., using computers) 
with consideration how much power they draw. 
 
5) Where appropriate, an effort will be made to recycle all waste produced during 
the study (e.g., cardboard boxes). 
 
 
 

DATA MANAGEMENT 
Data Type: 
Firstly, we will collect screening documents. This includes data from the online screening 
questionnaire on Qualtrics (see in documents the Online Screening questionnaire) which 
will check for essential inclusion and exclusion criteria for the study; and data collected in 
the online screening videocall and study visit 1 (see in documents the case record forms) 
which will be associated to a screening ID. This includes: 
- Demographic data (including ethnicity, gender, age, years in full-time education); 
- Information about the health of the participant (including past medical history, medication 
history and structured clinical interviews to identify current or past history of psychiatric 
disorders or sleep and circadian rhythm disorders); 
- Physiological measurements (weight, height, BMI calculation, blood pressure, pulse) and 
urine samples (for urine drug screening and urine pregnancy test for females at birth that 
will be recorded only as positive or negative) 
 
During screening, we will collect contact details for the purpose of this research only. If 
eligible in the online screening questionnaire, the prospective participant will be asked to 
provide an email contact after completing an online screening consent for this. When invited 
by email to book the online screening videocall, prospective participants will be asked to 
select a slot using Microsoft Bookings app of the university Nexus 365 for business account 
which collects their name and email address. In the video call screening session, they will 
also be asked for their personal contact details. 
 
Online consent forms will be collected electronically (on Qualtrics and exported as pdf). In-
person consent forms will be collected on PDF format (using an iPad pencil for signature) 
or paper form and will include participants’ names. 
 
Questionnaire responses and task results will be collected in the screening and study visits. 
Further questionnaire responses will be collected the day after study visit on an online 
questionnaire on Qualtrics. 
 
During one of the computer tasks at the study visit, three saliva samples will be collected by 
participants for salivary alpha-amylase analysis. 
 
Participant bank details will be collected for sharing with the finance team via electronic 
format for reimbursement of participants. 
Data Access 
Control?: 
No 
Data Storage 
Location: 
We will use an electronic trial master file (TMF) which will be stored in a University Nexus 
365 One drive folder and given access only to researchers working in the study through their 
password protected university accounts. The University Nexus 365 One drive uses Microsoft 
365 for business which guarantees encryption of data. The pseudonymised data associated 
only to a screening and participant identification (ID) numbers will be stored in a separate 
research data folder in the University Nexus 365 One drive. These will be shared with some 
members of the research team for the study. Some TMF folders and documents will be 
either stored separately (in digital or paper format) or will have a separate password for 
access as described below. 
 
The Microsoft Bookings app of the university Nexus 365 for business account will have an 
account linked to the study email and primary researchers accounts that will collect the 
participants name and email address for the purpose of booking the video call screening 
session. The in-person study visits bookings will also be sent to participants email using 

Microsoft Bookings app. This will not collect any other personal data and will not have the 
screening or participant ID numbers. 
 
The online screening questionnaire will be conducted and stored on Qualtrics and no IP 
addresses will be collected. The only information that will be collected will be the personal 
contacts to book the online screening videocall. 
 
Paper consent forms will be stored securely in a locked filing cabinet in a room in the 
Neurosciences Building (Department of Psychiatry). PDF consent forms will be stored in the 
respective eTMF folder accessible only by critical members of the research team. 
 
A participant enrolment log will link participants’ personal details to their unique (screening 
and participant) ID numbers. This document will be stored digitally in the respective folder 
of the TMF but with a separate password accessible only by critical members of the research 
team and separate from all research data. 
 
At the online screening videocall, personal/sensitive information (i.e., date of birth, name, 
address, contact number) will be stored separately to non-identifiable screening data (e.g., 
age, gender, educational level etc). The former will be stored digitally on a password 
protected document (Personal contacts) of the electronic TMF linked to a screening ID. 
While the latter screening data, will be stored digitally on the OneDrive research data folder. 
It will be linked to personal identifiers via the linkage code (Screening ID). 
 
The randomisation log and associated documents of the variance minimisation process will 
be stored in a separate folder in password-protected documents and will be linked to 
personal identifiers via the linkage code (Participant ID). These documents will only be 
accessible by Professor Cowen (or delegated to another study medic in his absence) and 
the independent researcher(s) that will manage the randomisation process. 
 
Saliva samples will be rendered acellular by centrifugation within 7 days and then samples 
will be stored in the Neurosciences Building (Department of Psychiatry) in a pseudo-
anonymised form at -20oC. Access to the samples will be by the research team and the 
samples will be held in the custody of the primary researcher who will hold the code linking 
the samples to a particular individual. 
 
Questionnaire and cognitive task data will be recorded on a digital format on the password-
protected OneDrive research data folder, de-identified and linked via linkage codes 
(screening and participant ID). Equally, the results of salivary alpha-amylase analyses will 
be stored in an electronic data sheet, using only the unique participant ID. Some data will 
be collected electronically using Qualtrics software and this data will be downloaded from 
Qualtrics and stored directly on the research data folder. All participant data will be stored 
under their screening or participant ID numbers. The cognitive task data will be backed up 
to a usb stick allocated to the project in a locked cabinet in a room in the Neurosciences 
Building (Department of Psychiatry). All research data storage will adhere to best practice 
guidance BPG09 ‘data security’. 
 
Participant bank details will be collected on an electronic document and shared with 
colleagues from the finance team via electronic format for bank transfer. 
Data Storage 
Period: 
Consent forms will be kept securely on paper or PDF for 10 years after the end of the study. 
 

Participants’ bank details will be sent electronically to the finance team and kept by them for 
7 years before being deleted. 
 
Personal/sensitive information stored in the electronic TMF, data from screening online 
questionnaires and the participant log that links participants’ personal details to their unique 
ID numbers will be destroyed after the study has concluded, and the results have been 
written up and published. 
 
The anonymised online screening responses of people that are not eligible to participate in 
the study and do not provide an email contact will be deleted from Qualtrics monthly. 
 
Other non-identifiable screening and research data, as well as the randomisation log will be 
archived and stored safely for 5 years after the final publication. Of note, this data will also 
be made available to the public and research community on data repository in line with Open 
Science Principles as described in the next question. The cognitive task data will be backed 
up to a usb stick allocated to the project in a locked cabinet in a room in the Neurosciences 
Building until the research data is processed, analysed and published. 
 
Any saliva samples labelled with the code linking the samples to a particular individual will 
be disposed of within six months according to HTA guidelines. The results of the salivary 
alpha-amylase analyses linked to the participant ID in an electronic data sheet will be 
deleted alongside other non-identifiable screening and research data 5 years after the final 
publication. 
Data Retention 
Reuse: 
In line with Open Science principles, this study will be preregistered on the Open Science 
Framework 
(https://osf.io/k6gmd/) 
and 
on 
the 
NIH 
Clinical 
Trials 
registry 
(https://clinicaltrials.gov/). 
 
On completion of full data analysis and manuscript submission we will make deidentified 
task and questionnaire data, along with relevant processing scripts, available to the public 
and research community on a data repository (Zenodo/GitHub) in line with Open Science 
Principles.  This will ensure long-term archiving and permit dataset accessibility/ discovery 
via common internet search engines. A Digital Object Identifier (DOI) link will be created for 
the dataset, enabling coupling to related publications. At no point will any of the data used 
for potential publication or presentation, or open science be linked to any personally 
identifiable information. 
 
Data which has been de-identified may be shared with other academic and commercial 
organisations in the future, including those outside of the UK and the EU. Participants will 
be informed of this and specific consent to this is obtained within the Informed Consent 
Form. 
 
For promotion in the Be Part of Research (BPoR) registry, we are required to provide 
monthly the information about how many participants heard about the study using BPoR. 
We will collect this data using one question on the online screening questionnaire that 
enquires about how they heard about the study. We will not provide any participant details 
to BPoR, except the frequency of cases that confirmed hearing about the study using the 
BPoR registry. 
Data 
Destruction: 
Once the study has concluded, the data has been analysed and the results have been 
written up and published , personal/sensitive information stored in the electronic TMF, data 
from screening online questionnaires on Qualtrics and the participant log that links 

participants’ personal details to their unique ID numbers will be destroyed by safely deleting 
the files. 
 
Any saliva samples labelled with the code linking the samples to a particular individual will 
be disposed of within six months on ending the study. 
 
Consent forms will be shredded or deleted 10 years after the end of the study. 
 
Participants’ bank details will be deleted by the finance team 7 years after the end of the 
study. 
 
The anonymised online screening responses of people that are not eligible to participate in 
the study and do not provide an email contact will be deleted from Qualtrics monthly. 
 
Other non-identifiable screening and research data, as well as the randomisation log will be 
safely deleted 5 years after the final publication. 
Data Access: 
Data stored physically will be kept in the physical trial folder, which alongside cognitive task 
data backed up to a project usb stick will be locked and secure in a filing cabinet located in 
a room which is locked when not in use (room located in the Neurosciences Building, 
Department of Psychiatry) and card-accessed. 
 
The electronic TMF folder and research data folder (with de-identified information linked to 
a unique ID number) on One drive will be shared with the research team for the study. 
However, some documents and folders in the TMF will have a separate password and 
access restrictions: 
- A participant enrolment log that links participants’ personal details to their unique ID 
numbers (screening and participant ID) will be stored under a separate password and 
accessible only by critical members of the research team, separate from all research data. 
- The Personal contacts log in the electronic TMF is a document with personal/sensitive 
information (i.e., date of birth, name, address, contact number and email address) and will 
have a separate password and will be accessible only by critical members of the research 
team. 
- The consent forms in PDF format are saved in a specific folder in the electronic TMF and 
will be accessible only by critical members of the research team. 
- The randomisation log and associated documents of the variance minimisation process 
will be stored separate in a folder only accessible to Professor Cowen (or delegated to 
another study medic in his absence) and the independent researcher(s) that will manage 
the randomisation process. The documents will be password-protected and will be linked to 
personal identifiers via the linkage code (Participant ID). These independent researchers 
will be provided with the participant ID and essential anonymised data (gender and 
chronotype MEQr score) for the randomisation process. 
 
The study email and the Microsoft Bookings app (part of the university Nexus 365 for 
business account) is linked to the primary researchers university accounts which require a 
password and a two-factor authenticator process to be accessed. 
 
In the unlikely event of a participant being involved in any safety incident at the 
Department of Psychiatry, their details (name) may be shared with safety officers, without 
any further personal information being shared. 
Organisation 
Data: 
No 

Recording: 
No 
Participant 
Data 
Confidentiality: 
The study will comply with the UK General Data Protection Regulation which requires data 
to be anonymised as soon as it is practical to do so. All participants details shared in 
screening questionnaire or visits will be treated as confidential by the research team and will 
be recorded as electronic data without name or address and assigned a study ID. A linking 
file will enable identification by matching the study ID to the participant name; this file will be 
stored securely and separately from the coded research data. All documents will be stored 
securely and only accessible by study staff and authorised personnel. 
Participant 
Data 
Anonymity: 
No 
Participant 
Data 
Pseudoanon: 
Yes 
Participant 
Data 
Pseudoanon 
More Info: 
Each participant will be assigned a unique study number at screening following informed 
consent to participate is confirmed. During the study, a key will link participants’ personal 
details to their unique study number in a document that will be stored separately from all 
research data. 
Both screening and study data will be stored pseudoanonymously (using study specific 
identifier - screening and participant ID) and will be retained for 5 years after publication and 
then destroyed, in line with Oxford University policy on the management of research data 
and records. 
Once the data has been analysed and the results have been published, the online screening 
data, contact information, participant enrolment log with the linking key will be destroyed. 
From then on, only annonomised data will be stored electronically. 
Publication: 
 
 

HUMAN TISSUE 
Training: 
Researcher name 
Title of course 
Date of completion 
Dr Daniela Almeida Borges 
Human Tissue Act training (MRC) 
26/11/2024 
Dr Michael Colwell 
Human Tissue Act training (MRC) 
20/05/2025 
Georgia Feltham 
Human Tissue Act training (MRC) 
12/01/2024 
Professor Catherine Harmer 
Human Tissue Act training (MRC) 
06/08/2024 
 
What samples: 
Urine; Saliva 
Samples previously collected and 
anonymised: 
No 
Amount collected (new samples): 
Urine – 30ml (Volume to be collected per participant) 
Saliva samples using Sarstedt salivettes - about 4.5ml in total (3 
samples of 1.5ml per participant) 
Relevant material: 
Yes 
Relevant material (yes): 
A license is not required. 
Urine is considered a relevant material under the Human Tissue 
Act. This study on healthy volunteers only includes the use of urine 
samples for baseline testing (for drug use and pregnancy) to 
confirm some of the exclusion criteria. It will only require the 
collection and immediate dipstick testing of the urine sample, with 
no storage, and the sample being destroyed on the day taken. As 
per Guidance on the registration of samples under an HTA licence 
at the University of Oxford (point 2.4.a on page 3), an HTA licence 
is only required if the samples are stored. 
Saliva is also considered a relevant material under the Human 
Tissue Act. However, the saliva samples will be rendered acellular 
by centrifugation within 7 days. Published work has shown that 
centrifugation at standard speeds (around 1,000–1,600 × g) is 
widely used to obtain cell-free saliva, and that further high-speed 
centrifugation can remove nearly all residual extracellular DNA 
and cell debris (Štibinger et al., 2019, Biomolecules). As our study 
deals with saliva samples rather than blood, that are collected in a 
synthetic swab, the protocols for rendering plasma acellular are 
not relevant in this context. We have also considered the salivettes 
manufacture guidance for the sample processing. Hence, we will 
complete centrifugation of the salivettes (1000xg for 2 minutes) 
within 4 hours of collection; transferring the supernatant to another 
tube and freeze it at -20o C; and finally dispose of the salivette 
collection tube (with the residue at the bottom) and the insert with 
synthetic swab in a hazardous biological waste container. 
Otherwise, the samples will be placed in the fridge and the 
centrifugation will take place within 7 days following the same 
steps. In these cases, the samples are viewed as acellular non-
HTA relevant samples and a licence is not required, provided that 
the processing takes a matter of hours or days and no longer than 
a week. 
Is transfer required: 
No 
DNA: 
No 
Is storage required: 
Yes 

Storage required (yes) 
Saliva samples will be de-identified and be assigned a linkage 
code to link participants with their respective samples. The 
samples will be rendered acellular by centrifugation within 7 days 
and then frozen. The salivette will be removed and destroyed after 
centrifugation. Prior to salivary alpha-amylase assay, the samples 
will be stored in the Neurosciences Building (Department of 
Psychiatry) in de-identified form at -20oC. The assays will be 
carried out in the Neurosciences Building. Access to the samples 
will be by the research team and the samples will be held in the 
custody of Professor Harmer. The primary researcher will hold the 
code linking the samples to a particular individual. Any excess 
acellular supernatant of saliva remaining at the end of the study 
will be disposed of within six months according to HTA guidelines. 
End of research: 
Disposal in accordance with the Human Tissue Act 2004 
 
 

DRUGS/SUBSTANCES 
CTIMP: 
No 
CTIMP no: 
In this trial we will use the dual orexin receptor antagonist daridorexant which is an 
oral medication licensed for the treatment of insomnia in adults in the UK (August 
2022). This drug was developed and is currently marketed by Idorsia 
Pharmaceuticals Limited Company. Daridorexant's efficacy for insomnia treatment 
was investigated in two multicentre, randomised, double-blind, placebo-controlled, 
parallel-group, Phase 3 studies, as well as its safety profile (Mignot, 2022). 
 
This study will assess daridorexant's non-clinical effects, i.e. reaction times or 
performance on emotional, reward and cognitive processing tasks in healthy 
subjects. Daridorexant is being used as a pharmacological tool to examine the 
effects of dual orexin receptor antagonism on emotion processing and cognition. 
The study is not a clinical trial under the scope of SI 1031. It will not investigate the 
efficacy and/or safety profile of daridorexant. Furthermore, it is not designed to 
discover, verify/compare the daridorexant’s clinical effects; to discover or 
verify/compare its pharmacological effects (e.g. pharmacodynamics); to identify or 
verify/compare its adverse reactions; or to study or verify/compare its absorption, 
distribution, metabolism or excretion as described by the MHRA. 
Local licence: 
Yes 
Local licence details: 
Daridorexant has a license as an oral medication for the treatment of insomnia in 
adults. We will be using this medication in healthy adult participants to assess non-
clinical effects of a dual orexin receptor antagonist. 
DSMB: 
No 
DSMB no: 
A Data and Safety monitoring board will not be required as this research study is 
not a Clinical Trial of an Investigative Medicinal Product. Furthermore, this study 
will not include vulnerable patients, will be delivered in a single centre with a low-
risk intervention. This study will follow a simple study design of a double-blind 
randomised controlled trial of daridorexant or placebo used once in the study 
location by healthy volunteers. As a research team, we will monitor data quality and 
safety as described in the methodology section. 
Sponsor: 
Does not apply. 
Drug detail: 
Name of drug/substance to 
be used 
Daridorexant 
Lactose and/or sucrose 
Purpose of use in this 
research 
For neuropsychological effects testing 
Placebo 
Adverse reactions and side 
effects posing a particular 
risk 
Common: Somnolence, Dizziness, Fatigue, 
headache and nausea. 
Uncommon: Hypersensitivity (including rash, 
urticaria); Hallucinations (Hypnagogic and 
hypnopompic); Abnormal dreams, nightmares; 
Somnambulism; Sleep paralysis 
N/A (placebo) 
Formulation 
Film-coated tablet will be encapsulated in 
opaque capsules 
Tablet (max dose of 
lactose 95mg) tablet will 
be encapsulated in 
opaque capsules 
Dose and route of 
administration for research 
50mg tablet for oral administration 
1 tablet for oral 
administration 

Duration of treatment for 
research 
Single dose 
Single dose 
Licence status where the 
research is taking place 
Licensed for use in the UK by MHRA  
N/A (inactive substance) 
Usual Indication 
Insomnia disorder in adults 
N/A (placebo) 
Usual Dose 
25 – 50 mg per day 
N/A (placebo) 
Dose to be used in research 
50mg 
1 tablet 
Usual duration of treatment 
Short-term, with review within 3 months and 
periodically thereafter. Clinical data are 
available for up to 12 months of continuous 
treatment. 
N/A (placebo) 
Duration of treatment in this 
research 
Single dose 
Single dose 
Source of drug/substance 
(name and address of 
manufacturer and/or 
supplier) 
Idorsia Pharmaceuticals Uk Limited 
Homeopathic Supply 
Company (HSC), UK 
Storage: 
The Daridorexant and placebo tablets will be stored at room temperature in a locked 
storage cupboard in the Neurosciences building. 
Dispensing: 
Daridorexant and placebo tablets will be dispensed from the Neurosciences 
building by a study medic. 
Preparation: 
Daridorexant and placebo will be over-encapsulated by study investigators and 
department staff by using the lab standard operating procedure (SOP). 
 
Each time a participant is assessed in screening processes as eligible, they will be 
randomly assigned to treatment or placebo using the variance minimisation 
algorithm to ensure an even distribution of key covariates (gender and chronotype 
/ MEQr score) between the groups. An independent researcher(s) will generate the 
randomisation code following the procedure described by Sella, Raz, and Cohen 
Kadosh (2021). They will then record the allocation on the Randomisation log, 
identify the correct envelope with the drug or placebo (previously encapsulated) 
and write the participant’s ID on it. This will then be ready for study researchers to 
collect and give to the respective participant in the study visit. 
Baseline safety: 
When participants express an interest in taking part in the study, they will be asked 
to complete an online consent for eligibility screening questionnaire to check for 
inclusion and exclusion criteria. The exclusion criteria were defined to mitigate the 
risk of daridorexant or placebo use in healthy adult volunteers. In particular, we 
considered to exclude participants with: 
 
1. Any sleep or circadian rhythm disorders (covered in in screening procedures); in 
particular narcolepsy for which daridorexant is contraindicated, as well as the risk 
of developing different sleep bheaviours, sedation and respiratory depression that 
might worsen sleep conditions. 
2. History of, receiving or seeking treatment for any mental health condition 
(covered in screening procedures); in particular due to risk worsening depression 
and suicidal ideation with daridorexant. 
3. History of, or current medical condition(s) which might increase the risk of oral 
administration of daridorexant: 

- ADHD requiring treatment with stimulants or other centrally-acting drugs 
- Neurological problems, including traumatic brain injury, epilepsy, Central Nervous 
System tumours or other severe neurological problems (e.g. Parkinson’s disease; 
blackouts requiring hospitalisation) 
- Current Asthma, Chronic Obstructive Pulmonary Disease, emphysema or any 
medical condition that affects the lungs or breathing 
- Mild to severe hepatic impairment (Child-Pugh class A-C) 
- Severe renal disease 
- Severe gastrointestinal problems 
- History of, or current medical condition(s) which, in the opinion of the Investigator 
may interfere with the safety of the participant or the scientific integrity of the study 
4. Pregnancy, intention to become pregnant or breastfeeding during the study, as 
this would be a contraindicated use of daridorexant. 
5. Body mass index (BMI) below 18 or above 30kg/m2, to ensure an appropriate 
pharmacokinetic profile for daridorexant is achieved. 
6. Current or past history of drug or alcohol dependency, and inability to withhold 
from alcohol within 24 hours of study visit as concomitant use with daridorexant 
increases postural instability and memory issues caused by alcohol. 
7. Regular alcohol consumption of more than 21 units per week or use of 
recreational drugs or performance-enhancing drugs (e.g. cannabis, cocaine, 
amphetamines) within past three months, and inability to withhold from alcohol 
within 24 hours of study visit as it might interact with daridorexant. 
8. Excessive caffeine consumption (above 400mg a day) as it could affect the sleep-
wake cycle influenced by daridorexant. 
9. Current or recent (past two months) use of any psychoactive medications, 
antihistamines, or medical device (e.g. implanted neurostimulator) that can cause 
sedation due similar effect profile of daridorexant and cumulative risk of sedation. 
10. Current use of any medications or substances at risk of interaction with 
daridorexant; in particular: 
- strong or moderate CYP3A inhibitors (e.g. strong inhibitors - itraconazole, 
clarithromycin, ritonavir, grapefruit juice; moderate inhibitors - fluconazole, 
verapamil, diltiazem, erythromycin, ciprofloxacin, cyclosporine) as these would 
increase risk of daridorexant side effects 
- strong or moderate CYP3A inducers (e.g. of strong inducers - rifampicin, 
carbamazepine, St. John’s wort; moderate inducers - bosentan, efavirenz, 
etravirine, modafinil) as these would reduce exposure to daridorexant. 
- Gastric pH-modifiers (e.g. famotidine and proton pump inhibitors) can decrease 
daridorexant maximum concentration 
- P-gp transporters (dabigatran, digoxin) as daridorexant can reduce effect of P-gp 
transporter drugs. 
11. Inability to ingest up to 95mg of lactose due to the potential use of placebo 
tablets. 
12. Previous participation in any other drug study or sleep intervention study in the 
last three months 
 
Participants that meet the eligibility screening criteria in the online screening 
questionnaire will be invited to the online screening videocall to continue the 
screening process. At the visit, they will first discuss and sign the consent form for 
study participation. Then, they will complete the required baseline screening 
interview, including: 
- Personal contact details collection 

- Demographic data including ethnicity, gender, age, years in full-time education 
- Medical history screening and details of current and past medication (including 
confirmation of exclusion criteria) 
- Selected sections of the Structured Clinical Interview for DSM-5 (SCID-5), which 
probes for past or current psychiatric illness (exclusion criteria) 
- Relevant screening questions for insomnia disorder (screen negative for insomnia 
symptoms on the Sleep Condition Indicator) and other sleep or circadian rhythm 
disorders (based on screening questions for other disorders identified by Wilson et 
al) 
 
At the first study visit (1), they will complete all measurements and investigations to 
confirm their eligibility for the study, including: 
- Weight and height measurement, for calculation of Body Mass Index (BMI) 
- Blood pressure and pulse recording at rest 
- Urine drug screening test 
- Urine pregnancy test (for female at birth) 
 
If they do not meet the eligibility criteria for the study at any of the screening 
procedures, the researcher will sensitively inform the participant they are ineligible 
and the screening process will end. 
If the outcomes of all screening procedures indicate the participant meets all of the 
study eligibility criteria, the participant will be enrolled in the study and assigned a 
participant ID. 
If screening or eligibility checks raise any questions about the participant’s 
suitability to take part in the study, the participant will still complete the baseline 
questionnaires and tasks at the screening visit. The researcher will ask a study 
medic during or after the screening videocall or study visit 1 to check information 
collected. The medical doctor might need to discuss the study with the participant 
and perform a medical examination, if deemed necessary. Participants will be 
informed of this and that they will be contacted with an outcome, if this is not 
completed at the screening visit. 
Safety Monitoring: 
If participants are eligible for the study, they will be invited for the second visit (Study 
visit 2) at the Neurosciences Building in the Department of Psychiatry and 
previously randomised to take daridorexant or placebo. A study medic will be 
available for phone advice and within 30-minute of the research site throughout the 
study visit period. A maximum of four weeks is allowed between the online 
screening videocall and the first Study Visit, as well as between the first and second 
study visits. If this duration is exceeded, another screening will be performed to 
ensure eligibility. 
 
We have considered the risk of sedation with daytime administration of 
daridorexant. Hence, we will organise the study visit in the morning as non-clinical 
evidence suggests that the risk of sedation with daridorexant is reduced in the first 
few hours after waking up (Roch et al., 2021 ). We will also ask participants to avoid 
certain substances that might interact with daridorexant or cause sedation (alcohol, 
recreational drugs, or grapefruit juice) 24 hours before the study visit. They will be 
asked to avoid smoking before the study visit, have a maximum of a cup of coffee 
(or equivalent) up to 90 minutes before the visit time and have a light breakfast (e.g. 
2 toasts of bread or yogurt with cereal). They will be asked to arrive via walking, 
being driven to, by public transport or taxi. They will otherwise be advised to 
complete their normal morning routine before study attendance. 

 
Before the study visit starts, we will check if participants still do not meet the 
exclusion criteria. Once they are administered the daridorexant or placebo tablets, 
they will be asked to stay at the Neurosciences building in a separate room and will 
be checked every 30 mins. They will only start cognitive tests 1 hour after 
administration. After administration and until the end of the study, participants will 
be asked to not eat food, drink caffeinated drinks or smoke. They will be 
encouraged to take comfort breaks. This is based on pharmacokinetics of 
Daridorexant (Muehlan et al., 2018; Boof et al., 2019; Muehlan et al., 2020; Berger 
et al., 2021). 
 
Their sleepiness state will be monitored using a validated one-item scale 
(Karolinska Sleepiness Scale) during the study visit. This will be checked before 
administration of daridorexant or placebo and hourly thereafter. Once the tasks are 
completed, they will be asked to continue to avoid driving or engaging in any 
activities requiring full alertness (e.g. cycling or operating heavy machinery) until 
the next morning. They will be advised that they should expect feeling completely 
back to normal the following day. However, if it happens that they feel drowsy, they 
will be advised not to carry out activities requiring full alertness. We will organise a 
taxi and/or public transport from the Warneford Hospital to their local 
accommodation, unless the participant has an equivalent transport arrangement 
(e.g. someone to drive them by car) already organised. If the Karolinska Sleepiness 
Scale is above 7 at the end of the study visit, we will organise a taxi. All participants 
will receive a phone number for calling the study medical doctor (Dr Borges) in case 
they need medical advice related to the study after the visit has taken place. We 
will also send a follow up questionnaire the next day to check on effects 
experienced and impact on sleep using the consensus sleep diary. 
 
The randomisation code will be broken if a participant requires treatment for a new 
medical condition or experiences serious adverse reactions, and either of these 
situations make it clinically important to know what medication they took. In order 
to unblind the participant, Professor Cowen or one of the independent researchers 
will access the randomisation log and will unblind the allocation if deemed 
necessary after discussion of the case. If breaking the code is necessary then only 
that individual’s code will be broken. Data from unblinded participants will not be 
admitted to analysis. If unblinding occurs, the researcher will record the reason and 
result of the unblinding, as well as the date and time of the event. 
Medical Cover: 
A medical doctor who is part of the research team will review the screening and 
make a final judgment about including participants in the study. A qualified medical 
doctor will be contacted if a participant expresses concern to a named researcher 
regarding side effects or health status changes during the course of the study. 
GP notification: 
No 
GP further info: 
Participants’ GPs will not be informed about their participation in the study. A one-
off dose of daridorexant is not regarded as a clinically significant intervention and 
is not expected to have any impact on participants’ health or wellbeing.