Randomized, placebo-controlled clinical trial to investigate the safety and efficacy of two dexamfetamine sulfate formulations in adults with ADHD and moderate to severe depression (DEXAD)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fraunhofer Institute For Translational Medicine And Pharmacology ITMP

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Behavior and Behavior Mechanisms [F01], Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

22 May 2025 → ongoing

Decision date (initial)

2025-02-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

MEDICE Arzneimittel Pütter GmbH & Co. KG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

to assess the incidence of adverse events in the active treatment groups (DEX IR and DEX XL) compared to placebo within the study period (V1 – V6)

Secondary objectives 9

1. Assessment of and comparison between the three treatment groups (DEX IR, DEX XL, placebo) of Adverse Events
2. Assessment of and comparison between the three treatment groups (DEX IR, DEX XL, placebo) of Suicidal ideation (score of the suicidal thoughts question of the MADRS)
3. Assessment of and comparison between the three treatment groups (DEX IR, DEX XL, placebo) of improvement of illness (CGI-I) at V5 compared to BL/V0
4. Assessment of and comparison between the three treatment groups (DEX IR, DEX XL, placebo) of improvement of severity of illness (CGI-S) at V5 compared to BL/V0
5. Assessment of and comparison between the three treatment groups (DEX IR, DEX XL, placebo) of depression rating by MADRS (Montgomery-Asberg-Depression Rating Scale)
6. Assessment of and comparison between the three treatment groups (DEX IR, DEX XL, placebo) of ADHD assessment by ADHS-DC-Q (Attention Deficit Hyperactivity Disorder Diagnostic Checklist Quantitative)
7. Assessment of and comparison between the three treatment groups (DEX IR, DEX XL, placebo) of assessment of depression by QIDS-SR-16 (Quick Inventory of Depressive Symptomatology)
8. Assessment of and comparison between the three treatment groups (DEX IR, DEX XL, placebo) of dose intake and compliance
9. Assessment of and comparison between the three treatment groups (DEX IR, DEX XL, placebo) of early study withdrawal

Conditions and MedDRA coding

Adults with ADHD and moderate to severe depression

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Diagnosis of attention deficit / hyperactivity disorder (ADHD) (according to DSM-5 or ICD guidelines) which started in childhood (at the age of <12 years)
2. Patient has a minimum ADHS-DC-Q total score of 32 at baseline (V0)
3. Moderate to severe depression according to ICD-10 (depressive episode: Code F32; recurrent depressive disorder: Code F33) and with a MADRS score of >20 at baseline (V0)
4. CGI-S ≥ 4 at baseline (V0)
5. Patients receiving SSRIs or SNRIs (stable doses within the last 2 weeks before inclusion) (≤40 mg (es)citalopram, 50-200 mg sertraline, 75 - 300 mg venlafaxine extended release)
6. Male or female patients ≥ 18 years and ≤ 65 at time of enrolment
7. Patients with QTc interval within normal ranges (≤470 ms in males and ≤480 ms in females)
8. Written informed consent and data protection declaration obtained prior to the initiation of any protocol required procedures
9. Willing and able to comply to study procedures and study protocol
10. Patient is either free of stimulant medication or who, after discussion with his / her treating physician, is able and willing to discontinue the current psychotropic medication(s) for treatment of ADHD symptoms (specifically, methylphenidate, lisdexamfetamine, guanfacine or atomoxetine or any other medication approved for the treatment of ADHD) ) for the duration of the study, as well as is able and willing to discontinue all relevant co-medication according to exclusion criterion no. 20a-s for comorbid conditions during the clinical trial, if applicable

Exclusion criteria 20

1. Current or a history of severe co-morbid symptoms such as psychotic symptoms, schizophrenia, bipolar disorders or manic episodes
2. Current or recent history of substance abuse disorder within the last 6 months of clinical trial entry
3. Patients with body mass index (BMI) < 18.5 kg/m² or >35 kg/m²
4. History of serotonin syndrome events
5. History of seizures or use of anticonvulsant medication
6. Any other uncontrolled psychiatric condition that requires medication or may interfere with trial participation
7. Known symptomatic cardiovascular disease including structural abnormalities, moderate and severe hypertension (systolic blood pressure ≥160 mmHg, diastolic blood pressure ≥100 mmHg), heart failure, myocardial infarction, arterial occlusive disease, angina, haemodynamically significant congenital heart disease, cardiomyopathies, potentially life-threatening arrhythmias and channelopathies (diseases caused by ion channel dysfunction)
8. Significant, in the discretion of the investigator, hepatic, gastrointestinal, renal, haematological or oncologic disorder
9. Diagnosis of glaucoma, hyperthyroidism, pheochromocytoma or porphyria
10. Diagnosis or family history of Tourette’s syndrome or dystonia
11. Pre-existing cerebrovascular disorders such as cerebral aneurysm, vascular abnormalities including vasculitis or stroke
12. Immunodeficiency disorders (e.g. organ transplantation, HIV infection)
13. Known hypersensitivity to any of the ingredients of the trial medication, e.g. patients with known rare hereditary problems of fructose intolerance
14. Males or females of reproductive potential not willing to use effective contraception (defined as PEARL index <1 - e.g. contraceptive pill, IUD) during the study period (Screening to Follow-up)
15. Pregnancy and lactation
16. Participation in another interventional clinical trial during the trial and within the previous 30 days prior to trial start
17. Patients who are institutionalised by court order or regulatory action
18. Patients, who are members of the staff of the trial centre, staff of the sponsor or involved Clinical Research Organisation (CRO), the investigator him- / herself or close relatives of the investigator
19. Legal incapacity and/ or other circumstances rendering the patient unable to understand the nature, scope and possible impact of the clinical trial
20. Current use and use within the last 2 weeks before inclusion of not permitted concomitant medication (as defined in protocol) due to possible interactions with stimulants or SSRIs/SNRIs and possible resulting or expected side effects:

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of adverse events (AE) in the active treatment groups (DEX XL and DEX IR) compared to the placebo until V6

Secondary endpoints 21

1. Incidence of adverse events (AE) until V5
2. Proportion of patients with at least one AE until V5 and until end of study
3. Number of AE until V5 and until end of study
4. Number of AE/SAE during the study period, number and proportion of patients with AE/SAE by type, severity (mild, moderate, severe) and relatedness to treatment
5. Score of CGI Efficacy index by investigator at Visit 5
6. MADRS suicidal ideation score (range 0-6) for all available visits (SCR to V5) and change to BL/V0 (only V1 to V5)
7. Rate of patients with score 1-3 in CGI-I at V5
8. Absolute scores categories of CGI-I at all available visits (V1 to V5)
9. Numbers and percentages of patients with (1) decreased, (2) maintained and (3) increased CGI-S at V5 compared to BL/V0
10. Shift table of CGI-S score categories at BL/V0, V1 and V5
11. Absolute score categories of CGI-S at all available visits (V0 to V5)
12. MADRS total score (range 0-60) for all available visits (SCR to V5) and change to BL/V0 (only V1 to V5)
13. MADRS total score categorization by Müller et al. (39) at BL/ V0, V1 and V5 (0-6 absence of symptoms; 7-19 mild depression, 20-34 moderate depression, 35-60 indicate a severe depression)
14. ADHS-DC-Q total score (range 0-66) for all available visits (SCR to V5) and change to BL/V0 (only V1 to V5)
15. QIDS-SR-16 total score (range 0-27) for all available visits (V0 to V5) and change to BL/V0 (only V1 to V5)
16. Mean dose intake from V1 to V5 per treatment group
17. Mean dose intake compared to planned dose after titration phase (for study period V1 to V5) per treatment group
18. Proportion of patients with less than 80% of planned dose intake (for study period V1 to V5) per treatment group
19. Number and proportion of patients by dosage group (DEX IR: 10 mg, 15 mg, 20 mg, 30 mg; DEX XL: 10 mg, 15 mg, 20 mg, 30 mg; Placebo: 10 mg, 15 mg, 20 mg, 30 mg)) at V1 and V2
20. Number and proportion of patients per treatment group that needed dose optimization of IMP in the optimal stable dose phase and type of optimization (e.g., downtitration)
21. Number and percentage of patients with early withdrawal from therapy due to adverse events - in total and per treatment group

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Placebo 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fraunhofer Institute For Translational Medicine And Pharmacology ITMP

Sponsor organisation

Fraunhofer Institute For Translational Medicine And Pharmacology ITMP

Address

Theodor-Stern-Kai 7, Sachsenhausen Sachsenhausen

City

Frankfurt Am Main

Postcode

60596

Country

Germany

Scientific contact point

Organisation

Fraunhofer Institute For Translational Medicine And Pharmacology ITMP

Contact name

Prof. Dr. med. Frank Behrens

Public contact point

Organisation

Fraunhofer Institute For Translational Medicine And Pharmacology ITMP

Contact name

Dr. Tanja Roßmanith

Third parties 1

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications