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

Attention Deficit Disorder With Hyperactivity Clinical Trial

— DAVE  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05621174
• Other study ID #: 82695
• Secondary ID: 2022-003237-1982
• Status: Recruiting
• Phase: N/A
• Start date: April 14, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: October 2023
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: Esra Pirgon, BSc
• Phone: +31 (0) 20 566 7048
• Email: e.pirgon[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 26
• Est. completion date: December 31, 2024
• Est. primary completion date: August 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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.

Related Conditions & MeSH terms

• Attention Deficit Disorder With Hyperactivity
• Hyperkinesis

Intervention

Drug:
• Dexamfetamine
Magisterial Dexamfetamine
• Dexamfetamine
Tentin

Locations

Country	Name	City	State
Netherlands	Glenn Dumont	Amsterdam	Noord-Holland

Sponsors (1)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Country where clinical trial is conducted

Netherlands, 

References & Publications (17)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Lader MH, Bond AJ. Interaction of pharmacological and psychological treatments of anxiety. Br J Psychiatry Suppl. 1998;(34):42-8. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Pourhoseingholi MA, Baghestani AR, Vahedi M. How to control confounding effects by statistical analysis. Gastroenterol Hepatol Bed Bench. 2012 Spring;5(2):79-83. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.	Before drug administration
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Blood samples	For analysis of the plasma concentration of dexamfetamine.	0-180 minutes after drug administration
Primary	Blood pressure	For autonomic and adverse effects measurements. Measured in mmHg Normal value: 120/80 mmHg	0-180 minutes after drug administration
Primary	Heart rate	For autonomic and adverse effects measurements. Measured in BPM Normal value: 60-100 BPM	0-180 minutes after drug administration
Secondary	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
Secondary	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
Secondary	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

External Links

•   Summary of Product Characteristics - DMB 5 mg
•   Summary of Product Characteristics - Tentin 5 mg