Primary Objective• P1. Verify if self-administered eye scanning using a smartphone application, using native key features (alone or in predefined combination(s)), can indicate use of each medicinal product (D1-D2).Secondary Objectives• S1. Verify if…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Substance use disorder (SUD)
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoint
P1. For each medicinal product (D1-D2), changes for each subject in key
features (alone or in predefined combination(s)) between baseline at visit 2
and under the influence of D1-D2 at LC-MS/MS defined peak concentration, using
native key features.
Secondary outcome
Secondary Endpoints
S1. For each medicinal product (D1-D2), changes for each subject in key
features (alone or in predefined combination(s) as described in the primary
endpoint, see SAP), between baseline at visit 2 and under the influence of
D1-D2 at LC-MS/MS defined peak concentration, using refined key features.
S2. For each medicinal product (D1-D2), changes in refined key features alone
or in predefined combination(s), between baseline and under the influence of
D1-D2 at 10 min and up to 7 h after medicinal product administration. The
comparison is only made using the 5 key features with the lowest p-values from
S1.
S3. For each subject, differences between refined key features taken at the
clinic (baseline visit 2) and measurements taken in home environment under
similar light conditions. This will be performed only with Dbase, Dcon, MCA,
MCV. Two different ambient light conditions, as measured with the smartphones,
will be compared for dimmed (20-119 Lux) and bright (120-500 Lux) light.
S4. For each medicinal product (D1-D2), differences between refined key
features (for the 5 key features with lowest p-value as found in S1, or in
predefined combination(s)) observed for the cohort collected under the
influence of D1-D2 at peak LC-MS/MS defined peak concentration, and
observations collected for the cohort when drug naive (baseline visit 2). In
this analysis data will be analyzed at group level (drug influenced and drug
naive) without using intra-individual changes. (Hence, the groups are handled
as two independent cohorts).
Safety Endpoint
The incidence and severity of adverse events associated with Previct Drugs.
Background summary
Previct Drugs is a CE-marked eHealth system developed by the Kontigo Care AB
intended to be used in treatment of substance use disorder (SUD) to support and
monitor patients' treatment at a distance. Previct Drugs is a standalone
medical device software classified as a class I medical device according to the
Medical Device Regulation (EU) (MDR) 2017/745. Previct Drugs eye scanning
function is implemented in a smartphone application (app), which uses the
smartphone*s camera to record videos of the pupil and eye movement, and the
resulting data is processed to indicate drug usage. Previct Drugs is thereby a
portable device easily used by the user in the home environment.
Previct Drugs is one of the devices developed by Kontigo Care AB that belongs
to the Previct platform. The Previct platform consists of two CE-marked
devices; Previct Alcohol to be used within treatment and monitoring of alcohol
and Previct Drugs to be used within treatment and monitoring of SUD.
This investigation is designed as a PMCF investigation to collect additional
clinical data to verify the performance and safety of Previct Drugs and enhance
the already existing models for indicating the use of cannabinoids and
phenethylamines. Previct Drugs will in this investigation be used in accordance
with the CE-mark. The results from two previous pre-market clinical
investigations, KCClin01 and KCClin02, showed that opioids, phenethylamines,
benzodiazepines, and cannabinoids can be detected with Previct Drugs using
smartphone-based eye scanning (SES). The results were based on administration
of four medicinal products mimicking the use of illicit drugs: Oxycodone
(opioid), Lisdexamphetamine (phenethylamine), Lorazepam (benzodiazepine), and
Bedrocan (cannabinoid). The dosing of the medicinal products used resembled to
a therapeutic dose used in clinic for treatment of diseases. The models were
excellent (AUC= ~0.9) for indicating the use of opioids and benzodiazepines,
i.e., clinical dosing was high enough. For phenethylamines the models were
acceptable (AUC = ~0.7-0.8). For cannabinoids the effect was statistically
significant but due to too low dosing giving low plasma concentrations, they
did not properly depict illicit drugs use as the abused doses for cannabinoids
are much higher than the therapeutic doses. Therefore, this investigation aims
to collect additional data for verifying the performance and safety of Previct
Drugs under intake of cannabinoids and phenethylamines. The doses to be used in
a controlled single administration in this investigation will be increased
compared to the KCClin01 investigation, but still correspond with previously
safely used dosing in clinical investigations.
The drug intake will in this PMCF investigation be simulated through collecting
SES data using Previct Drugs before and after a controlled single
administration of commonly used medicinal products from the following classes
of drugs: phenethylamines (D1) and cannabinoids (D2). For making this possible,
a healthy volunteer population has been suggested as the most appropriate
investigation population for being able to collect clinical data before and
after the single application of the medicinal product. The population will
consist of 30 healthy volunteers (12 for phenethylamines and 18 for
cannabinoids) recruited in the Netherlands. Each subject will participate in
the investigation for approximately 7-10 days after the baseline and screening
visit.
Study objective
Primary Objective
• P1. Verify if self-administered eye scanning using a smartphone application,
using native key features (alone or in predefined combination(s)), can indicate
use of each medicinal product (D1-D2).
Secondary Objectives
• S1. Verify if self-administered eye scanning using a smartphone application,
after refinement of the method for establishing key features (alone or in
predefined combination(s)), can indicate the use of each medicinal product
(D1-D2).
• S2. Evaluate the first and last time after medicine intake of D1 or D2 when
refined key eye features, alone or in predefined combination(s), differ from
baseline.
• S3. Evaluate the difference between refined drug naïve test data collected at
the clinic and compared with tests performed in home environment.
• S4 Evaluate if the refined drug naïve key features (alone or in predefined
combination(s)), collected at baseline differs from data collected at peak
plasma concentration under the influence of D1-D2 without compensating for
intra-individual variation.
Safety objective
Verify the safety of using the smartphone application Previct Drugs for
collecting self-administered eye scanning data.
Study design
This is a post-market clinical follow-up (PMCF) investigation designed to
collect additional clinical data on Previct Drugs to verify its performance and
safety, and to improve its drug identification capacity with self-administered
smartphone-based eye scanning (SES). The clinical data collected in this
clinical investigation is an important step to verify and improve the developed
algorithms of the CE-marked system, and to improve the mathematical models for
indicating the use of cannabinoids and phenethylamines.
The design of this third clinical investigation KCClin03 is similar to the
previously conducted pre-market clinical investigation KCClin01, where the eyes
of healthy volunteers were monitored with Previct Drugs before and after intake
of one out of four medicinal products (opioids, benzodiazepines,
phenethylamines, or cannabinoids). Also, in this investigation will
therapeutically used medicinal products be used during a controlled single
administration where Previct Drugs will be used before and after the intake.
The substances that will be used are: phenethylamines (30 mg Dexamphetamine -
D1) and cannabinoids (Bedrocan (100 mg, containing 22% tetrahydrocannabinol
(THC) - D2)). The dosing will be increased with approximately 50% in this
investigation compared to KCClin01 to ensure higher plasma concentrations and
stronger eye scanning responses compared to KCClin01, and thus a better ability
to mimic illicit substance use. This investigation will also use Dexamphetamine
instead of Lisdexamphetamine that was used in the KCClin01 investigation due to
that Dexamphetamine has a faster Tmax (peaks at 1.5h) compared to
Lisdeaxamphetamine that is a slow-release formulation. In total will 20 key
features be analysed with Previct Drugs of which seven are new key features to
estimate nystagmus and eyelid movements.
Previct Drugs is a CE-marked eHealth system composed of an app and a
careportal, intended to be used in treatment of substance use disorder (SUD) to
support and monitor patients* treatment. The app is used by patients to perform
drug sobriety tests using eye-scanning and report on assigned tasks as defined
by the individual treatment plan. The drug sobriety test relies on the analysis
of the eye*s reaction on intake of drug substances and gives an indication of
the following substances: opioids, benzodiazepines, central stimulants (e.g.,
amphetamine and other phenethylamines). The test may also indicate intake of
high doses of cannabinoids and alcohol. The careportal is used by healthcare
professionals to create individual treatment plans and to receive the results
on the patient*s treatment adherence and drug sobriety progress.
This investigation will use Previct Drugs per current CE-mark, but there will
be some minor differences as some modules/functionalities are not applicable to
be used per investigation design and that the study population consists of
healthy volunteers which is not the target population of Previct Drugs.
Although, the usage and performance of Previct Drugs is the same and therefore
it is being used as per CE-mark. The minor differences are:
• The Previct Drugs app will have the following functionality deactivated to
enable the clinical investigation to be performed:
- Instead of displaying information on drug intake, a message will be displayed
in the app after performing a text, *Thank you for your test*.
- The calibration step will be omitted.
- Follow-up steps, if indication of drugs has been identified will be omitted.
These steps are not required based on that the population in this investigation
will be healthy volunteers.
• The careportal will be used for providing a subject access to the app and
registration of the used smartphone*s identity. The sponsor Kontigo Care will
administrate this. The careportal*s functionality and modules normally used by
the caregiver will not be available and used in this clinical investigation.
• An external computer will be used for the analysis of the collected data from
the app. The external computer/analysis will be handled by the sponsor, Kontigo
Care.
• A healthy volunteer population will be used instead of the target population
of Previct Drugs to be able to collect data before and after administration of
a medicinal product. The population enrolled will be as per eligibility
criteria and thereby within the age limitation of Previct Drugs.
The investigation will enroll and follow-up adult male and female healthy
volunteers, i.e., subjects, for collection of baseline data during one week in
the subject*s home environment and thereafter performance of a single
administration of one of the two medicinal products of interest (D1 and D2) at
the site in a controlled setting.
Intervention
Visit 1 at the site:
- Scan they eyes with Previct Drugs 6 times (demonstration and training not
included)
- Health examination (e.g., ECG, pulse, blood pressure)
- Urine pregnancy test for fertile female subjects
- Urine test for drug screening
- Questionnaires to be answered by subject
At home between visits 1 and 2:
- Scan the eyes with Previct Drugs 4 times/day (once in the morning, two during
the day, and once in the evening) for 1 week (+ 4 days/- 2 days)
Visit 2 at the site:
- Urine pregnancy test for fertile female subjects
- Urine test for drug screening
- Vital signs: oxygen saturation in blood, pulse, blood pressure, temperature
- Scan the eyes with Previct Drugs for 26 times cannabinoids and 28 times for
phenethylamines
- Singel administration of the medicinal product
- Collection of blood samples for LC-MS/MS analysis
Telephone follow up
- Confirm safety
Study burden and risks
The risks of using smartphone-based eye scanning through Previct Drugs is very
low. Therefore, the main risk of this investigation is related to the
administration of the medicinal product, cannabinoids and phenethylamines, and
the side effects which they may have. This has been minimized by using a single
administration of the medicinal product, that the subjects are under continuous
surveillance on the clinic, and the dosing is within used range used for
therapeutic purposes. A second risk is dependence, which is considered as very
low as during inclusion we exclude all subjects with any kind of psychiatric
disorder and addiction tendency, and we use only a single dose of the medicinal
product. The subjects them-self have no direct benefit of the investigation,
but it is very common that there is a relative or a friend which have problem
with substance use.
Bangårdsgatan 4A
Uppsala 753 20
SE
Bangårdsgatan 4A
Uppsala 753 20
SE
Listed location countries
Age
Inclusion criteria
1. Male or female healthy volunteers.
2. Age 18 to 55 years.
3. BMI between 18.5-30 kg/m2.
4. Weight between 50-100 kg.
5. Healthy as determined by the investigator or designee based on
pre-investigational medical and surgical history, and health examination at
enrollment.
6. 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 clinical
investigation completion.
7. No current drug usage defined as a negative urine drug test at enrollment
and at visit 2.
8. Able to use Previct Drugs after initial training (defined as successfully
performing a test set after trying maximum three times per measurement).
9. Voluntarily agrees to participate and has duly singed the Informed Consent
Form.
Exclusion criteria
1. Participating in another clinical investigation which may affect the
clinical investigation outcome according to clinical judgement.
2. Previously participated in the KCClin01 investigation.
3. Pregnant or lactating.
4. Blind and/or deaf.
5. Clinically abnormal ECG, according to the investigator. QTcF time >450 ms at
enrollment.
6. Resting heart rate >90 BPM.
7. Current or recent history of alcohol misuse assessed by AUDIT where >=6
points for women or >=8 points for men indicates a potential misuse.
8. Current or history of psychiatric disorder or drug misuse assessed by
M.I.N.I where the outcome will be based on clinical judgement.
9. Any disease or condition that may influence pupillary reflexes based on
clinical judgement.
10. Undergone eye surgery that may influence pupillary reflexes based on
clinical judgement.
11. Ongoing treatment with medications which may interfere with eye
measurements based on clinical judgement.
12. Ongoing treatment with medications which may interfere with any of the
medicinal products to be used.
13. History or presence of allergy or serious reaction to the medicinal
products to be used.
14. History or presence of cardiovascular disease, e.g., arteriosclerosis,
hypertension, or cor pulmonale.
15. History or presence of sleep-related breath disorder.
16. History or presence of gastrointestinal disease, e.g., paralytic ileus,
acute abdomen, delayed gastric emptying, or chronic constipation.
17. History or presence of pulmonary disease, e.g., acute pulmonary
insufficiency, severe respiratory depression with hypoxia, chronic obstructive
lung disease, or bronchial asthma.
18. History or presence of autoimmune neuromuscular disease, e.g., myasthenia
gravis.
19. Not able to read or understand the local language.
20. Any other condition that as judged by the investigator may make the
follow-up or investigation inappropriate.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT06629740 |
| CCMO | NL87202.058.24 |