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

Not Applicable

Completed

Conditions: Drug Abuse

Interventions: Device: Previct Drugs

Registration Number: NCT05731999

Lead Sponsor: Kontigo Care AB

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 48

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Single application of benzodiazepines (D2)	Previct Drugs	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.
Single application of phenethylamines (D1)	Previct Drugs	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.
Single application of opioids (D4)	Previct Drugs	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.
Single application of cannabinoids (D3)	Previct Drugs	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.

Primary Outcome Measures

Name	Time	Method
Use of 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).	Day 7 +/- 2 days (Visit 2)	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. A key feature represents an eye characteristic (such as pupil size, iris position, and the similar). A successful transformation is characterised by underlying quality control algorithms approving the extracted magnitude, where poor quality pupillograms are rejected from analysis. Each attempt to transform a pupillogram into key features is denoted an "Attempt", and the successful transformation is denoted a "Successful attempt".

Secondary Outcome Measures

Name	Time	Method
Number of Key Features for Which Correlation Between Pupillometric Variables and Concentration in Plasma Over Time is Significant for Each Medicinal Product D1-D4 and Ambient Light Condition.	Day 7 +/- 2 days (Visit 2)	For each medicinal product (D1-D4), number of significant correlations between key features and plasma concentration over time using refined pupillograms. A key feature represents an eye characteristic (such as pupil size, iris position, and the similar). A key feature is considered "correlated" if the slope in a linear regression is significantly different from zero (p\<0.05). The term correlated over time refers to data collected during 5 hours at Visit 2 after administration of D1-D4. Key features were available from two conditions, one condition where pupillograms and corresponding key features were collected in dim ambient light (50 Lux) and one condition where pupillograms and corresponding key features were collected in bright ambient light (500 Lux). The Outcome Measure is reported for both ambient light conditions.
Use of 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).	Day 7 +/- 2 days (Visit 2)	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. A key feature represents an eye characteristic (such as pupil size, iris position, and the similar). A successful transformation is characterised by underlying quality control algorithms approving the extracted magnitude, where poor quality pupillograms are rejected from analysis. Each attempt to transform a pupillogram into key features is denoted an "Attempt", and the successful transformation is denoted a "Successful attempt.
Number of Key Features With Change From Baseline to Peak Concentration in Plasma, Using Refined Pupillograms.	Day 7 +/- 2 days (Visit 2)	For each medicinal product (D1-D4), number of changed 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 refined pupillograms. Each of the 24 key features represents an eye characteristic (such as pupil size, iris position, and the similar). A key feature is considered "changed" if the difference between averages at baseline and peak concentration is significant (p\<0.05). Key features were available from two conditions, one condition where pupillograms and corresponding key features were collected in dim ambient light (50 Lux) and one condition where pupillograms and corresponding key features were collected in bright ambient light (500 Lux). The Outcome Measure is reported for both ambient light conditions.
Number of Key Features With Change From Baseline to 5 Hours After Administration of Medicinal Product, Using Refined Pupillograms.	Day 7 +/- 2 days (Visit 2)	For each medicinal product (D1-D4), number of changed key features from baseline to 5 hours after administration of medicinal product at visit 2 using refined pupillograms. A key feature represents an eye characteristic (such as pupil size, iris position, and the similar). A key feature is considered "changed" if the difference between averages at baseline and at 5 hours is significant (p\<0.05). Key features were available from two conditions, one condition where pupillograms and corresponding key features were collected in dim ambient light (50 Lux) and one condition where pupillograms and corresponding key features were collected in bright ambient light (500 Lux). The Outcome Measure is reported for both ambient light conditions.
Number of Correct Classifications of Subjects, Evaluated Using a Combination of Different Pupillometric Variables for Indicating Use of Each Medicinal Product D1-D4 and Ambient Light Condition.	Day 7 +/- 2 days (Visit 2)	For each medicinal product (D1-D4), evaluate 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 refined pupillograms. A key feature represents an eye characteristic (such as pupil size, iris position, and the similar). A combination of key features collected at peak plasma concentration was used to build a logistic regression classifier, and the resulting counts of true positives, true negatives, false positives, and false negatives are presented. Key features were available from two conditions, one condition where pupillograms and corresponding key features were collected in dim ambient light (50 Lux) and one condition where pupillograms and corresponding key features were collected in bright ambient light (500 Lux). The Outcome Measure is reported for both ambient light conditions. Key feature values were missing in a few instances, as shown in the table.
Usability Questionnaire - Question 1	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 1. How would you grade the instructions for use? Response options: * Not understandable * Could only understand some parts * Could understand most parts * Could understand almost every part * Fully understandable
Usability Questionnaire - Question 2	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 2. Was Previct Drugs easy to use correctly based on the information in the Instructions For Use (IFU)? Response options: * Yes * No
Usability Questionnaire - Question 4	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 4. How did you experience the verbal instructions during a test with Previct Drugs? Response options: * Very easy to understand * Easy to understand * Nor easy or difficult to understand * Difficult to understand * Very difficult to understand
Usability Questionnaire - Question 5	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 5. Before starting a test, the App prompted you with a few written instructions. Did you read the instructions? Response options: * Yes * No
Usability Questionnaire - Question 7	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 7. How did you experience performing a test with Previct Drugs (from opening of the App until the test was completed)? Response options: * Very easy to perform * Easy to perform * Nor easy or difficult to perform * Difficult to perform * Very difficult to perform
Usability Questionnaire - Question 8	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 8. During a test with Previct Drugs, did you at any time have to tilt the mobile against something to be able to perform a measurement? Response options: * Yes * No
Usability Questionnaire - Question 9	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 9. If Yes (to question 8), how often did you have to tilt the mobile against something: Response options: * One occasion * Several occasions * Most occasions * All occasions
Usability Questionnaire - Question 10	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 10. According to you, how many minutes did a test with Previct Drugs take in general? From start to end. Response options: * \< 5 minutes * 5-7 minutes * \> 7 minutes
Usability Questionnaire - Question 11	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 11. Did you receive a notification when it was time for a test with Previct Drugs? Response options: * Yes * Most of the times * I did not receive any notifications
Usability Questionnaire - Question 12	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 12. Did you notice any issues during usage of Previct Drugs? Response options: * No * Yes
Usability Questionnaire - Question 13	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 13. Did you require any assistance from the study personnel (e.g., through phone) during the usage of Previct Drugs? Response options: * Yes * No
Usability Questionnaire - Question 15	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 15. If Yes (to question 13), how often did you require assistance? Response options: * One occasion * Several occasions * Most occasions * All occasions
Usability Questionnaire - Question 16	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 16. When starting a measurement, how was your experience finding the right conditions to start the measurement? Response options: * Very easy * Easy * Nor easy or difficult * Difficult * Very difficult
Usability Questionnaire - Question 18	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 18. How did you experience performing a Nystagmus (look to your extreme right and left) test? Response options: * Very easy to perform * Easy to perform * Nor easy or difficult to perform * Difficult to perform * Very difficult to perform
Usability Questionnaire - Question 20	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 20. According to you, how many minutes did a Nystagmus test take (from starting test until analyzed)? Response options: * \< 1 minute * 1-2 minutes * \> 3 minutes
Usability Questionnaire - Question 21	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 21. How often did you have to redo a Nystagmus test? Response options: * No occasion * One occasion * Several occasions * Most occasions * All occasions
Usability Questionnaire - Question 23	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 23. In general, how easy is it for you to cross your eyes? Response options: * Very easy * Easy * Nor easy or difficult * Difficult * Very difficult
Usability Questionnaire - Question 24	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 24. How did you experience performing a Cross Eyes test? Response options: * Very easy to perform * Easy to perform * Nor easy or difficult to perform * Difficult to perform * Very difficult to perform
Usability Questionnaire - Question 26	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 26. According to you, how many minutes did a Cross Eyes test take (from starting until analyzed)? Response options: * \< 1 minute * 1-2 minutes * \> 3 minutes
Usability Questionnaire - Question 27	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 27. How often did you have to redo a Cross Eyes test? Response options: * No occasion * One occasion * Several occasions * Most occasions * All occasions
Usability Questionnaire - Question 29	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 29. How did you experience performing a Contraction test? Response options: * Very easy to perform * Easy to perform * Nor easy or difficult to perform * Difficult to perform * Very difficult to perform
Usability Questionnaire - Question 31	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 31. How was your experience turning your mobile when asked to? Response options: * Very easy to perform * Easy to perform * Nor easy or difficult to perform * Difficult to perform * Very difficult to perform
Usability Questionnaire - Question 33	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 33. According to you, how many minutes did a Contraction test take (from starting test until analyzed)? Response options: * \< 1 minute * 1-2 minutes * \> 3 minutes
Usability Questionnaire - Question 34	Day 7 +/- 2 days (Visit 2)	User-friendliness of Previct Drugs evaluated by the subject at visit 2. Question 34. How often did you have to redo a Contraction test? Response options: * No occasion * One occasion * Several occasions * Most occasions * All occasions