Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2022-003237-19 | EudraCT Number | ||
| 82695 | Registry Identifier | Centrale Commissie Mensgebonden Onderzoek (CCMO) |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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:
Researchers will compare the outcomes between magisterial dexamphetamine and Tentin use in a crossover setting.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Magisterial Dexamphetamine | Other | Magisterial Dexamphetamine |
|
| Tentin | Other | Tentin |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dexamfetamine | Drug | Magisterial Dexamfetamine |
|
| 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 |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Leeds Sleep Evaluation Questionnaire (LSEQ) | 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. |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Glenn JH Dumont, PhD | Amsterdam UMC | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Glenn Dumont | Amsterdam | North Holland | 1105AZ | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16966188 | Background | Lott DC, Kim SJ, Cook EH, de Wit H. Serotonin transporter genotype and acute subjective response to amphetamine. Am J Addict. 2006 Sep-Oct;15(5):327-35. doi: 10.1080/10550490600859868. | |
| 5554941 | Background | Martin WR, Sloan JW, Sapira JD, Jasinski DR. Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther. 1971 Mar-Apr;12(2):245-58. doi: 10.1002/cpt1971122part1245. No abstract available. |
| Label | URL |
|---|---|
| Summary of Product Characteristics - DMB 5 mg | View source |
Not provided
Privacy protocol
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D001289 | Attention Deficit Disorder with Hyperactivity |
| ID | Term |
|---|---|
| D019958 | Attention Deficit and Disruptive Behavior Disorders |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D003913 | Dextroamphetamine |
| ID | Term |
|---|---|
| D000661 | Amphetamine |
| D000662 | Amphetamines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Dexamfetamine | Drug | Tentin |
|
|
| 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 |
| 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 |
| Before drug administration |
| 9807980 | Background | Wong YN, Wang L, Hartman L, Simcoe D, Chen Y, Laughton W, Eldon R, Markland C, Grebow P. Comparison of the single-dose pharmacokinetics and tolerability of modafinil and dextroamphetamine administered alone or in combination in healthy male volunteers. J Clin Pharmacol. 1998 Oct;38(10):971-8. doi: 10.1002/j.1552-4604.1998.tb04395.x. |
| 28936175 | Background | Dolder PC, Strajhar P, Vizeli P, Hammann F, Odermatt A, Liechti ME. Pharmacokinetics and Pharmacodynamics of Lisdexamfetamine Compared with D-Amphetamine in Healthy Subjects. Front Pharmacol. 2017 Sep 7;8:617. doi: 10.3389/fphar.2017.00617. eCollection 2017. |
| 31916494 | Background | Dan O, Cohen A, Asraf K, Saveliev I, Haimov I. The Impact of Sleep Deprivation on Continuous Performance Task Among Young Men With ADHD. J Atten Disord. 2021 Jul;25(9):1284-1294. doi: 10.1177/1087054719897811. Epub 2020 Jan 9. |
| 6777817 | Background | Parrott AC, Hindmarch I. The Leeds Sleep Evaluation Questionnaire in psychopharmacological investigations - a review. Psychopharmacology (Berl). 1980;71(2):173-9. doi: 10.1007/BF00434408. |
| 14696019 | Background | Tarrasch R, Laudon M, Zisapel N. Cross-cultural validation of the Leeds sleep evaluation questionnaire (LSEQ) in insomnia patients. Hum Psychopharmacol. 2003 Dec;18(8):603-10. doi: 10.1002/hup.534. |
| 29534726 | Background | Manzar MD, Salahuddin M, Maru TT, Alghadir A, Anwer S, Bahammam AS, Pandi-Perumal SR. Validation of the adapted Leeds sleep evaluation questionnaire in Ethiopian university students. Health Qual Life Outcomes. 2018 Mar 13;16(1):49. doi: 10.1186/s12955-018-0876-0. |
| 5908477 | Background | Haertzen CA. Development of scales based on patterns of drug effects, using the addiction Research Center Inventory (ARCI). Psychol Rep. 1966 Feb;18(1):163-94. doi: 10.2466/pr0.1966.18.1.163. No abstract available. |
| 14048539 | Background | HILL HE, HAERTZEN CA, WOLBACH AB Jr, MINER EJ. THE ADDICTION RESEARCH CENTER INVENTORY: STANDARDIZATION OF SCALES WHICH EVALUATE SUBJECTIVE EFFECTS OF MORPHINE, AMPHETAMINE, PENTOBARBITAL, ALCOHOL, LSD-25, PYRAHEXYL AND CHLORPROMAZINE. Psychopharmacologia. 1963 May 15;4:167-83. doi: 10.1007/BF02584089. No abstract available. |
| 9829016 | Background | Lader MH, Bond AJ. Interaction of pharmacological and psychological treatments of anxiety. Br J Psychiatry Suppl. 1998;(34):42-8. |
| 27444046 | Background | Setnik B, Roland CL, Pixton G, Webster L. Measurement of Drug Liking in Abuse Potential Studies: A Comparison of Unipolar and Bipolar Visual Analog Scales. J Clin Pharmacol. 2017 Feb;57(2):266-274. doi: 10.1002/jcph.801. Epub 2016 Aug 23. |
| 9368198 | Background | Ahearn EP. The use of visual analog scales in mood disorders: a critical review. J Psychiatr Res. 1997 Sep-Oct;31(5):569-79. doi: 10.1016/s0022-3956(97)00029-0. |
| 31541305 | Background | Ashinoff BK, Abu-Akel A. Hyperfocus: the forgotten frontier of attention. Psychol Res. 2021 Feb;85(1):1-19. doi: 10.1007/s00426-019-01245-8. Epub 2019 Sep 20. |
| 25052243 | Background | Schmid Y, Hysek CM, Simmler LD, Crockett MJ, Quednow BB, Liechti ME. Differential effects of MDMA and methylphenidate on social cognition. J Psychopharmacol. 2014 Sep;28(9):847-56. doi: 10.1177/0269881114542454. Epub 2014 Jul 22. |
| 24834204 | Background | Pourhoseingholi MA, Baghestani AR, Vahedi M. How to control confounding effects by statistical analysis. Gastroenterol Hepatol Bed Bench. 2012 Spring;5(2):79-83. |
| 23741561 | Background | Kang H. The prevention and handling of the missing data. Korean J Anesthesiol. 2013 May;64(5):402-6. doi: 10.4097/kjae.2013.64.5.402. Epub 2013 May 24. |
| Summary of Product Characteristics - Tentin 5 mg | View source |
| D000588 |
| Amines |
| D009930 | Organic Chemicals |