A First Study in Healthy Volunteers of a New Mobile Phone Application Measuring the Eyes Before and After Medication

Study Overview
=================
Brief Summary
-----------------
This is a pre-market, explorative, early feasibility, pilot, controlled clinical investigation designed to collect initial clinical data on the medical device Previct Drugs.

Detailed Description
-----------------
This first study will give valuable information on the feasibility of Previct Drugs function to measure pupils and eye movements and to evaluate if there are any changes in the pupillometric parameters before and after intake of a medicinal product. It will also provide information on the usability of the device. Drug intake will in this first investigation be simulated by a controlled single application of commonly therapeutically used medicinal products from the following classes of drugs: phenethylamines (D1), benzodiazepines (D2), cannabinoids (D3), and opioids (D4).

Official Title
-----------------
A First-in-human Explorative Pilot Study in Healthy Volunteers Measuring Eye Parameters With a New Mobile Phone Application for Future Monitoring of Patients in Treatment of Substance Use Disorder

Conditions
-----------------
Drug Abuse

Intervention / Treatment
-----------------
* Device: Previct Drugs


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female healthy volunteers Age 18 to 70 years BMI between 18.5-30 kg/m2 Weight between 50-100 kg Healthy as determined by the investigator or designee based on pre-study medical and surgical history and a health examination at enrollment Women of childbearing potential (defined as all women who are not surgically sterile or postmenopausal for at least 1 year prior to enrollment) must have a negative urine pregnancy test at enrollment and at visit 2 and must agree to use a medically acceptable contraception from enrollment until study completion No current drug usage defined as a negative urine drug test at enrollment and at visit 2 Able to use Previct Drugs after initial training (defined as successfully performing a test after trying maximum three times per measurement) Been informed of the nature, the scope, and the relevance of the clinical investigation Voluntarily agreed on participation and has duly singed the Informed Consent Form Exclusion Criteria: Participating in another clinical investigation which may affect the study outcome according to clinical judgement Pregnancy or Lactating Blind Deaf Abnormal ECG (QTc time >450 ms) at enrollment Current or recent history of alcohol misuse assessed by AUDIT where ≥6 points for women or ≥8 points for men indicates a potential misuse Current or history of psychiatric disorder or drug misuse assessed by M.I.N.I where the outcome will be based on clinical judgement Any disease or condition that may influence pupillary reflexes based on clinical judgement Undergone eye surgery that may influence pupillary reflexes based on clinical judgement Ongoing treatment with medications which may interfere with eye measurements based on clinical judgement Ongoing treatment with medications which may interfere with any of the medicinal products to be used History or presence of allergy or serious reaction to the medicinal products to be used History or presence of cardiovascular disease, e.g., arteriosclerosis, hypertension, or cor pulmonale History or presence of sleep-related breath disorder History or presence of gastrointestinal disease, e.g., paralytic ileus, acute abdomen, delayed gastric emptying, or chronic constipation History or presence of pulmonary disease, e.g., acute pulmonary insufficiency, severe respiratory depression with hypoxia, chronic obstructive lung disease, or bronchial asthma History or presence of autoimmune neuromuscular disease, e.g., myasthenia gravis Not able to read or understand the local language Any other condition that as judged by the investigator may make the follow-up or investigation inappropriate That according to the Declaration of Helsinki is deemed unsuitable for study enrollment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be randomized to one out of four arms, i.e., single application of either phenethylamines, benzodiazepines, cannabinoids, or opioids. The investigation aims to enroll 11 subjects, i.e., healthy volunteers, per medicinal product group that have completed the clinical investigation until the telephone follow-up call. For four medicinal products, the total will be 44 subjects. In order to take account for a drop-out rate of 10%, 12 subjects will be included per medicinal product group and in total 48 subjects in the clinical investigation. As this is an early feasibility and explorative investigation, the sample size is not derived from a sample size calculation as no hypothesis is pre-defined.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single application of phenethylamines (D1)<br>Evaluation of Previct Drugs' function to measure pupils and eye movements and to evaluate if there are any changes in the pupillometric parameters before and after intake of phenethylamines. | Device: Previct Drugs<br>* Previct Drugs is a new non CE-marked eHealth system intended to be used for future monitoring and treatment of patients with substance use disorder (SUD). Previct Drugs consists of an application (app) to be installed on a smartphone, a web-based careportal to be accessed from a computer by the healthcare professional for administration and access of registered data, and a database for storage, handling, and analysis of reported data. Previct Drugs is intended to be used by healthcare professionals and patients within treatment of SUD.<br>|
| Experimental: Single application of benzodiazepines (D2)<br>Evaluation of Previct Drugs' function to measure pupils and eye movements and to evaluate if there are any changes in the pupillometric parameters before and after intake of benzodiazepines. | Device: Previct Drugs<br>* Previct Drugs is a new non CE-marked eHealth system intended to be used for future monitoring and treatment of patients with substance use disorder (SUD). Previct Drugs consists of an application (app) to be installed on a smartphone, a web-based careportal to be accessed from a computer by the healthcare professional for administration and access of registered data, and a database for storage, handling, and analysis of reported data. Previct Drugs is intended to be used by healthcare professionals and patients within treatment of SUD.<br>|
| Experimental: Single application of cannabinoids (D3)<br>Evaluation of Previct Drugs' function to measure pupils and eye movements and to evaluate if there are any changes in the pupillometric parameters before and after intake of cannabinoids. | Device: Previct Drugs<br>* Previct Drugs is a new non CE-marked eHealth system intended to be used for future monitoring and treatment of patients with substance use disorder (SUD). Previct Drugs consists of an application (app) to be installed on a smartphone, a web-based careportal to be accessed from a computer by the healthcare professional for administration and access of registered data, and a database for storage, handling, and analysis of reported data. Previct Drugs is intended to be used by healthcare professionals and patients within treatment of SUD.<br>|
| Experimental: Single application of opioids (D4)<br>Evaluation of Previct Drugs' function to measure pupils and eye movements and to evaluate if there are any changes in the pupillometric parameters before and after intake of opioids. | Device: Previct Drugs<br>* Previct Drugs is a new non CE-marked eHealth system intended to be used for future monitoring and treatment of patients with substance use disorder (SUD). Previct Drugs consists of an application (app) to be installed on a smartphone, a web-based careportal to be accessed from a computer by the healthcare professional for administration and access of registered data, and a database for storage, handling, and analysis of reported data. Previct Drugs is intended to be used by healthcare professionals and patients within treatment of SUD.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate if self-administered pupillometry using a mobile phone application can be used to collect pupillograms before and under the influence of phenethylamines, benzodiazepines, cannabinoids, and opioids (D1-D4). | For each medicinal product (D1-D4), the fraction of collected pupillometry data from the mobile phone application at baseline and under the influence of D1-D4, which can be transformed into pre-defined key features using native pupillogram. | At Visit 2 (Day 7 +/- 2 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate if self-administered pupillometry using a mobile phone application, after refining the method for establishing pupillograms, can be used to collect pupillograms before and under the influence of each medicinal product (D1-D4). | For each medicinal product (D1-D4), the fraction of collected pupillometry data from the mobile phone application at baseline and under the influence of D1-D4, which can be transformed into pre-defined key features using refined pupillogram. | At Visit 2 (Day 7 +/- 2 days) | 
| Evaluate if self-administered pupillometry using a mobile phone application can be used for indicating use of each medicinal product (D1-D4). | For each medicinal product (D1-D4), change in key features from baseline to the LC-MS/MS (Liquid Chromatography Tandem Mass-Spectroscopy) verified peak concentration in plasma after administration of medicinal product at visit 2 using native or refined pupillograms. | At Visit 2 (Day 7 +/- 2 days) | 
| Evaluate the correlation between pupillometric variables and concentration in plasma over time for each medicinal product D1-D4. | For each medicinal product (D1-D4), analysis and plot the correlation between key features and plasma concentration over time using native or refined pupillograms. | At Visit 2 (Day 7 +/- 2 days) | 
| Evaluate the maximum time after medicine intake D1-D4 when pupillometric variables differ from baseline. | For each medicinal product (D1-D4), change in key features from baseline to 5 hours after administration of medicinal product at visit 2 using native or refined pupillograms. | At Visit 2 (Day 7 +/- 2 days) | 
| Evaluate if a combination of different pupillometric variables can be used for indicating use of each medicinal product D1-D4. | For each medicinal product (D1-D4), test known combinations of key features that changes from baseline to the LC-MS/MS verified peak concentration in plasma after administration of medicinal product at visit 2 using native or refined pupillograms. | At Visit 2 (Day 7 +/- 2 days) | 
| Collect usability data to evaluate if the user-interface of Previct Drugs is suitable to be used by users. | User-friendliness of Previct Drugs evaluated by the subject at visit 2. The subject will fill out a study specific device usability questionnaire. | At Visit 2 (Day 7 +/- 2 days) |