The Difference in the Mechanism of Action Between Two Brands of Dexamfetamine in Adults With ADHD

Study Overview
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Brief Summary
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The goal of this clinical trial is to compare in the pk/pd profiles of magisterial dexamfetamine and Tentin in adults with Attention Deficit Hyperactivity Disorder (ADHD). The main question[s] it aims to answer are: Q1: is there a difference between pk/pd profiles of the two forms of dexamfetamine? Q2: how does the pharmacokinetic variability influences the objective and subjective (side) effects experienced by adult patients with ADHD? Participants will: take the Quantified behavior Test for analysis of objective effects. undergo blood sampling for analysis of the plasma concentration of dexamphetamine. undergo blood pressure and heart rate measurements. fill out 4 types of questionnaires. Researchers will compare the outcomes between magisterial dexamphetamine and Tentin use in a crossover setting.

Detailed Description
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Objectives The primary objective is to compare the pharmacological profile of the magisterial form of dexamfetamine sulfate to the pharmacological profile of the brand-name form of dexamfetamine (Tentin©) in adult patients diagnosed with attention deficit hyperactivity disorder (ADHD) and assess whether there is a difference between pk/pd profiles of the two forms of dexamfetamine. The secondary objective is to assess how pharmacokinetic variability influences the objective and subjective (side) effects experienced by adult patients with ADHD. Measurements At three moments (0, 60 and 120 minutes after drug administration) on each intervention-day, participants will complete the QbTest to assess objective performance and the QbPerformance to assess subjective performance. At eight moments (0, 45, 60, 75, 90, 120, 150 and 180 minutes after drug administration) on each intervention-day, participants will undergo blood sampling to determine dexamfetamine plasma concentrations and vital sign measurements for safety monitoring and possible outcome-effects. At eight moments (0, 45, 60, 75, 90, 120, 150 and 180 minutes after drug administration) on each intervention-day, participants will fill out questionnaires to assess subjective experiences.

Official Title
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The Difference in Pharmacodynamic and Pharmacokinetic Profiles Between Tentin and Magisterial Dexamfetamine in Adults With Attention Deficit Hyperactivity Disorder, a Double Blinded Randomised Crossover-controlled Trial

Conditions
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Attention Deficit Disorder With Hyperactivity

Intervention / Treatment
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* Drug: Dexamfetamine
* Drug: Dexamfetamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is aged ≥ 18 years at time of screening. Participant is diagnosed with ADHD according to the DSM 5 criteria. Participant has switched from Tentin© to magisterial dexamfetamine due to the adverse effects of Tentin. Participant is being treated adequately with dexamphetamine, as determined by their practitioner, at time of screening. Participant or their legal representative is able and willing to provide written informed consent. Participant is able and willing to comply with the study protocol (e.g. swallow capsules, have blood samples taken, can visit the outpatient clinic twice). Participant has not participated in another study in the past three months. Exclusion Criteria: Participant has a disorder that might affect drug absorption (e.g. gastrointestinal, metabolic, endocrine or liver disorder). Participant is allergic to the ingredients of the capsules.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Magisterial Dexamphetamine<br>Magisterial Dexamphetamine | Drug: Dexamfetamine<br>* Magisterial Dexamfetamine<br>* Other names: Magisterial Dexamfetamine;|
| Other: Tentin<br>Tentin | Drug: Dexamfetamine<br>* Tentin<br>* Other names: Tentin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantified behavior Test (QbTest) - Time Active | Time Active for analysis of objective effects. The Quantified behaviour Test (QbTest) provides data to assess the three core symptoms of ADHD, that is: hyperactivity, inattention and impulsivity. Time Active (in %) is one of the scores used to measure hyperactivity, inattention and impulsivity. For the current study cardinal outcomes will be derived from a Principal Component Analysis. | 0-120 minutes after drug administration | 
| Quantified behavior Test (QbTest) - Distance | Distance for analysis of objective effects. The Quantified behaviour Test (QbTest) provides data to assess the three core symptoms of ADHD, that is: hyperactivity, inattention and impulsivity. Distance (in meters) is one of the scores used to measure hyperactivity, inattention and impulsivity. For the current study cardinal outcomes will be derived from a Principal Component Analysis. | 0-120 minutes after drug administration | 
| Quantified behavior Test (QbTest) - Area | Area for analysis of objective effects. The Quantified behaviour Test (QbTest) provides data to assess the three core symptoms of ADHD, that is: hyperactivity, inattention and impulsivity. Area (in cm2) is one of the scores used to measure hyperactivity, inattention and impulsivity. For the current study cardinal outcomes will be derived from a Principal Component Analysis. | 0-120 minutes after drug administration | 
| Quantified behavior Test (QbTest) - Micro Events | Micro Events for analysis of objective effects. The Quantified behaviour Test (QbTest) provides data to assess the three core symptoms of ADHD, that is: hyperactivity, inattention and impulsivity. Micro Events (in millimeters) is one of the scores used to measure hyperactivity, inattention and impulsivity. For the current study cardinal outcomes will be derived from a Principal Component Analysis. | 0-120 minutes after drug administration | 
| Quantified behavior Test (QbTest) - Motion Simplicity | Motion Simplicity for analysis of objective effects. The Quantified behaviour Test (QbTest) provides data to assess the three core symptoms of ADHD, that is: hyperactivity, inattention and impulsivity. Motion Simplicity (in %) is one of the scores used to measure hyperactivity, inattention and impulsivity. For the current study cardinal outcomes will be derived from a Principal Component Analysis. | 0-120 minutes after drug administration | 
| Blood samples | For analysis of the plasma concentration of dexamfetamine. | 0-180 minutes after drug administration | 
| Blood pressure | For autonomic and adverse effects measurements. Measured in mmHg Normal value: 120/80 mmHg | 0-180 minutes after drug administration | 
| Heart rate | For autonomic and adverse effects measurements. Measured in BPM Normal value: 60-100 BPM | 0-180 minutes after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Addiction Research Centre Inventory (ARCI) - Acute Subjective Response to Substances (ASRS): Amphetamine Scale | Subjective effects measurement In this trial, only amphetamines will be administered, therefore only the first 11 questions of the amphetamine-scale will be used. The investigators have adjusted the 'true-false' questions in the amphetamine-scale to Visual Analog Scale (VAS)-questions, since VASs are more sensitive to subtle changes than Likert-scales and VAS enables rapid completion leading to a lower participant burden. The ARCI questions 1 t/m 11 are in line with the therapeutic effects of dexamfetamine. For each question, the VAS can be marked between 0 and 10 cm, 0 meaning 'not at all' and 10 meaning 'very much' when answering the questions. | 45-180 minutes after drug administration | 
| Bond-Lader Visual Analog Scale (BL-VAS) | Subjective effects measurement The Bond & Lader VAS Mood Rating Scale (BL-VAS) is used to measure the effects of drugs on the participants' mood. It consists of 16 dimensions (VAS) of mood. Ultimately, these dimensions are combined to create the following dimensions: alertness, contentedness, and calmness. For each question, the VAS can be marked between 0 and 10 cm, 0 meaning 'not at all' and 10 meaning 'very much' when answering the questions. | 0-180 minutes after drug administration | 
| QbTest performance questionnaire | Subjective effects measurement QbPerformance to assess subjective performance on the QbTest. For 1 question, a 'yes' or 'no' answer will be given. For 3 questions, the VAS can be marked between 0 and 10 cm, 0 meaning 'not at all' and 10 meaning 'very much' when answering the questions. | 0-180 minutes after drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Attention Deficit Disorder with Hyperactivity, Attention Deficit Hyperactivity Disorder, ADHD, ADD, AD(H)D