A prospective, multicentre, randomised, double-dummy, double-blind, placebo-controlled 3-way Phase III study to investigate the efficacy and safety of two dexamfetamine sulfate formulations in adults with ADHD - DEXINA -

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medice Arzneimittel Puetter GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Psychological Phenomena [F02], Diseases [C] - Nervous System Diseases [C10]

Trial duration

5 Nov 2025 → ongoing

Decision date (initial)

2024-03-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To investigate the efficacy of immediate-release dexamfetamine sulfate (DEX IR) tablets and modified-release dexamfetamine sulfate (DEX XL) capsules in comparison to placebo in adult patients with ADHD.

Secondary objectives 1

1. To investigate the safety of DEX IR tablets and DEX XL capsules in comparison to placebo in adult patients with ADHD.

Conditions and MedDRA coding

Patients with ADHD (according to ICD-10 / DSM-5)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Signed informed consent and data protection declaration prior to initiation of any trial procedures
2. Male or female adult patient ≥18 years of age at time of enrolment
3. Diagnosis of attention deficit / hyperactivity disorder (ADHD) based on a detailed psychiatric evaluation using a validated semi-structured interview tool (i.e. Wender-Reimherr Adult Attention Deficit Disorder Scale [WRAADDS], German Version: Wender-Reimherr Interview [WRI] or equivalent) a) in patients with no diagnosis based on a detailed psychiatric evaluation using a validated semi-structured interview tool and b) in patients diagnosed via a validated semi-structured interview tool such as WRI longer than 12 month ago
4. Confirmation of onset of ADHD in childhood (at the age of <12 years) using the WURS-k questionnaire for retrospective assessment
5. Patient has a minimum ADHS-DC-Q total score of 32 at Screening (Visit -2)
6. Patient has a minimum CGI-S score of 4 at Screening (Visit -2)

Exclusion criteria 30

1. A History or presence of inflammatory bowel disease (IBD); Crohn's disease in particular can lead to an altered absorption of active pharmaceutical ingredients
2. A history or presence of pronounced anacidity of the stomach with a pH value above 5.5, in therapy with H2 receptor blockers, proton pump inhibitors or in antacid therapy
3. Bariatric surgery (also known as metabolic surgery or weight loss surgery) is a surgical procedure used to manage obesity and obesity-related conditions as these conditions could have a negative impact on the retardation of the study medication
4. History of serotonin syndrome events
5. Any severe psychiatric condition that requires medication
6. Pre-existing cardiovascular disorders), heart failure, myocardial infarction, peripheral occlusive disease, angina pectoris, haemodynamically significant congenital heart defects, cardiomyopathies, potentially life-threatening arrhythmias and channelopathies (diseases caused by ion channel dysfunction)
7. Uncontrolled hypertension, defined as systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg, or the presence of hypertension without appropriate antihypertensive medication, regardless of current blood pressure values.
8. Significant hepatic, gastrointestinal, renal, haematological or oncologic disorder
9. Diagnosis of current glaucoma, hyperthyroidism, pheochromocytoma or porphyria
10. Diagnosis or family history of Tourette's syndrome or dystonia (Tic disorders (F95) and dystonias (G24), if they are associated with functional impairments.
11. Pre-existing cerebrovascular disorders such as cerebral aneurysm, vascular abnormalities including vasculitis or stroke
12. Any severe psychiatric condition that requires medication
13. Immunodeficiency disorders (e.g., organ transplantation, HIV infection)
14. Known hypersensitivity to any of the ingredients of the trial medication (Patients with the rare hereditary fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase deficiency) or known hypersensitivity or idiosyncrasy to sympathomimetic amines
15. Women of child-bearing potential who do not use a highly effective method of contraception (at least 4 weeks prior study), that is the case when the Pearl Index of the contraceptive measure is ≥1, Women who are in a homosexual relationship and women without a relationship/partner do not have to use a highly effective contraception method unless they have heterosexual sex
16. Pregnancy and lactation
17. Participation in another interventional clinical trial during the trial and within the previous 30 days prior to trial start
18. Patients who are institutionalised by court order or regulatory action
19. 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
20. Pre-existing cardiovascular disorders including moderate and severe hypertension (systolic blood pressure ≥160 mmHg, diastolic blood pressure ≥100 mmHg), heart failure, myocardial infarction, etc.
21. History or presence of severe depression, history or presence of anorexia nervosa / anorectic disorders, psychotic symptoms, severe affective disorders, schizophrenia, mania, psychopathic / borderline personality disorders
22. History or Presence (6 months prior to Visit -2) of suicidal ideation (e.g. type 4 or type 5 according to Columbia Suicide Severity Rating Scale [C-SSRS])
23. Known previous non-response to dexamfetamine sulfate
24. Newly initiated behavioural, cognitive or cognitive-behavioural therapy or change in frequency of sessions within 3 months prior to Visit 0 (except for ADHD coaching which is no psychotherapy)
25. A history of alcohol abuse or substance abuse disorder (exclusively nicotine abuse)
26. Positive urine drug test at Visit -2 and, if applicable, also at Visit -1 (except for patients taking bupropion)
27. Legal incapacity and/ or other circumstances rendering the patient unable to understand the nature, scope and possible impact of the clinical trial
28. Known to be or suspected of being unable to comply with the clinical trial protocol
29. Use of prohibited co-medication within 14 days prior to Visit 0: anticonvulsants, benzodiazepines, psychostimulants other than the IMP, antipsychotics, monoamine oxidase (MAO) inhibitors, lithium, guanfacine, clonidine, systemically administered ephedrine and pseudoephedrine, amantadine, coumarins, phenylbutazone, antacids and proton pump inhibitors
30. Change of antidepressants including bupropion due to psychiatric condition within 3 months prior to Visit 0

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. The two primary endpoint families will be tested in hierarchical order separately for the respectiv test of • DEX IR tablets versus Placebo • DEX XL capsules versus Placebo
2. 1.1a Change in the total score of the ADHS-DC-Q at the end of the Optimal Stable Dose Phase (Visit 5) compared to baseline (Visit 0)
3. 1.1b Change in the total score of the SDS at the end of the Optimal Stable Dose Phase (Visit 5) compared to baseline (Visit 0)
4. 1.2 Treatment failure defined as:- Percentage change of at least 30% in the total score of the ADHS-DC-Q scale at the end of the LTFU / Withdrawal Phase compared to the beginning of the LTFU / Withdrawal Phase (Visit 5) - 2. Percentage change greater than -30% in the total score of the ADHS-DC-Q scale at the end of the LTFU / Withdrawal Phase (Visit 9) compared to baseline (Visit 0)

Secondary endpoints 2

1. CGI-I Score at the end of the Optimal Stable Dose Phase (Visit 5)
2. Change in CGI-S Score at the end of the Optimal Stable Dose Phase (Visit 5) and EOT (Visit 9) compared to baseline (Visit 0)

Investigational products

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

Test 5

Placebo 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medice Arzneimittel Puetter GmbH & Co. KG

Sponsor organisation

Medice Arzneimittel Puetter GmbH & Co. KG

Address

Kuhloweg 37, Kuhlo Kuhlo

City

Iserlohn

Postcode

58638

Country

Germany

Scientific contact point

Organisation

Medice Arzneimittel Puetter GmbH & Co. KG

Contact name

Dr. Anke Mayer

Public contact point

Organisation

Medice Arzneimittel Puetter GmbH & Co. KG

Contact name

Dr. Anke Mayer

Third parties 3

Locations

1 EU/EEA country · 24 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 2 · Art. 38 CTR

Results and documents

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

Documents 55 files

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

Application history

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