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

Sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05621174

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

4.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Attention Deficit Disorder With Hyperactivity	Drug: Dexamfetamine Drug: Dexamfetamine	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

26 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Other

Official Title:

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

Anticipated Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Other: Magisterial Dexamphetamine Magisterial Dexamphetamine	Drug: Dexamfetamine Magisterial Dexamfetamine Other Names: Magisterial Dexamfetamine
Other: Tentin Tentin	Drug: Dexamfetamine Tentin Other Names: Tentin

Arm

Intervention/Treatment

Other: Magisterial Dexamphetamine

Magisterial Dexamphetamine

Drug: Dexamfetamine

Magisterial Dexamfetamine

Other Names:

Magisterial Dexamfetamine

Other: Tentin

Tentin

Drug: Dexamfetamine

Tentin

Other Names:

Tentin

Outcome Measures

Primary Outcome Measures

Quantified behavior Test (QbTest) - Time Active [0-120 minutes after drug administration]
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.
Quantified behavior Test (QbTest) - Distance [0-120 minutes after drug administration]
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.
Quantified behavior Test (QbTest) - Area [0-120 minutes after drug administration]
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.
Quantified behavior Test (QbTest) - Micro Events [0-120 minutes after drug administration]
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.
Quantified behavior Test (QbTest) - Motion Simplicity [0-120 minutes after drug administration]
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.
Blood samples [0-180 minutes after drug administration]
For analysis of the plasma concentration of dexamfetamine.
Blood pressure [0-180 minutes after drug administration]
For autonomic and adverse effects measurements. Measured in mmHg Normal value: 120/80 mmHg
Heart rate [0-180 minutes after drug administration]
For autonomic and adverse effects measurements. Measured in BPM Normal value: 60-100 BPM

Secondary Outcome Measures

Addiction Research Centre Inventory (ARCI) - Acute Subjective Response to Substances (ASRS): Amphetamine Scale [45-180 minutes after drug administration]
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.
Bond-Lader Visual Analog Scale (BL-VAS) [0-180 minutes after drug administration]
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.
QbTest performance questionnaire [0-180 minutes after drug administration]
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.

Other Outcome Measures

Leeds Sleep Evaluation Questionnaire (LSEQ) [Before drug administration]
Sleep deprivation can negatively impact attention functioning in adults with and without ADHD. Sleep deprived participants performed worse on the QbTest. Therefore, the sleep quality of participants must be taken into account. The Leeds Sleep Evaluation Questionnaire (LSEQ) consists of ten bipolar 100mm visual analogue scales (VAS) questions that are associated with sleep. The LSEQ covers the following four aspects of sleep, namely: getting to sleep, quality of sleep, awakening from sleep and behavior following wakefulness (F1-CRF). The LSEQ has provided evidence for validity in clinical research. Furthermore, the LSEQ has been cross-culturally validated in multiple countries and languages. The LSEQ is a consistent, reliable and validated tool to evaluate sleep and should therefore be included in the current study. Participants will be asked to fill in the questionnaire once at baseline (T=0), since it only evaluates the sleep quality of participants of the night before.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 64 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.