A prospective multi-centric, 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 -
- Trial ID
- 2022-502903-31-00
- Protocol
- 6520-9970-08
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of immediate-release dexamfetamine sulfate (DEX IR) tablets and modified-release dexamfetamine sulfate (DEX XL) capsules compared to placebo in adult patients diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) according to ICD-10/DSM-5 criteria. This is clinically relevant as it aims to determine the therapeutic potential of these formulations in managing symptoms of ADHD, which can significantly impact daily functioning and quality of life.
Secondary objectives include investigating the **safety** of DEX IR tablets and DEX XL capsules in comparison to placebo in the same patient population. Assessing safety is crucial to ensure that the benefits of the treatment outweigh any potential risks, thereby providing a comprehensive understanding of the treatment's overall profile.
Participants
The clinical trial involves **adult patients** diagnosed with Attention Deficit Hyperactivity Disorder (**ADHD**) as per ICD-10 or DSM-5 criteria. The study population includes both male and female participants aged 18 years and older. Participants were selected based on a detailed psychiatric evaluation using validated semi-structured interview tools, with confirmation of ADHD onset in childhood. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants' general health status is not specified, and there are no specific lifestyle considerations such as diet or physical activity mentioned. Key inclusion criteria include a minimum ADHS-DC-Q total score of 32 and a minimum CGI-S score of 4 at screening. The trial aims to assess the efficacy of immediate-release and modified-release dexamfetamine sulfate compared to placebo in this population.
Plans and Procedures
The clinical trial is a **randomized**, double-dummy, double-blind, placebo-controlled Phase III study designed to evaluate the efficacy and safety of two formulations of **dexamfetamine sulfate** in adults diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) according to ICD-10/DSM-5 criteria. The trial will involve a comparison between immediate-release dexamfetamine sulfate tablets, modified-release dexamfetamine sulfate capsules, and placebo. The study is expected to commence recruitment on March 4, 2024, and conclude by September 30, 2025, with a maximum treatment period of 44 weeks for participants.
Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on inclusion criteria such as age (≥18 years), a confirmed diagnosis of ADHD, and specific scores on the WURS-k and ADHS-DC-Q scales. Following successful screening, participants will be randomized into one of the treatment arms. The trial will include multiple follow-up visits to monitor efficacy and safety, with primary endpoints focusing on changes in the ADHS-DC-Q and SDS scores at the end of the Optimal Stable Dose Phase (Visit 5) compared to baseline (Visit 0). Secondary endpoints will assess changes in the CGI-I and CGI-S scores.
The expected duration of participant involvement is up to 44 weeks, with conditions for early termination including significant adverse events or non-compliance with the study protocol. The end-of-study visit will evaluate the long-term follow-up and withdrawal phase outcomes, with treatment failure defined by specific percentage changes in the ADHS-DC-Q scale scores. The trial's design ensures rigorous assessment of the investigational products' efficacy and safety, contributing valuable data to the understanding of ADHD treatment in adults.
Treatment
The clinical trial involves the administration of several **dexamfetamine sulfate** formulations and placebo controls. The primary experimental medications include **Dexamfetamine sulfate** in modified-release capsule form, available in dosages of 20 mg, 15 mg, and 10 mg. These capsules are designed for oral administration and are produced by MEDICE ARZNEIMITTEL PÜTTER GMBH & CO KG. The maximum daily dose for these formulations is 20 mg, with a total maximum dose of 6160 mg over a treatment period of 44 weeks. The active substance, **dexamfetamine sulfate**, is of chemical origin and classified under the ATC code N06BA02. The modified-release capsules are not formulated for pediatric use.
Additionally, the trial includes the use of **Attentin** tablets, available in 5 mg and 10 mg dosages. These tablets also contain **dexamfetamine sulfate** as the active ingredient and are intended for oral administration. The tablets are manufactured by MEDICE ARZNEIMITTEL PÜTTER GMBH & CO. KG and share the same maximum daily and total dose limits as the modified-release capsules. The tablets are similarly not designed for pediatric use.
Placebo controls are utilized in the study to ensure the validity of the results. The placebos are labeled as "Placebo for test 1" and "Placebo for test 2," with dosages of 5 mg, 10 mg, 15 mg, and 20 mg. These placebos do not contain any active substances and are not associated with any specific pharmaceutical form or route of administration. The use of placebos is integral to the double-blind, placebo-controlled design of the trial, allowing for the assessment of the efficacy and safety of the experimental medications in comparison to inactive controls.
Efficacy
The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include the 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), and the change in the total score of the SDS at the same time points. Additionally, treatment failure is defined by a 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 this phase (Visit 5), or a percentage change greater than -30% at the end of the LTFU/Withdrawal Phase (Visit 9) compared to baseline (Visit 0).
Secondary endpoints include the CGI-I Score at the end of the Optimal Stable Dose Phase (Visit 5) and the change in CGI-S Score at the end of the Optimal Stable Dose Phase (Visit 5) and at the end of treatment (Visit 9) compared to baseline (Visit 0). These efficacy parameters will be measured using validated scales and patient-reported outcomes at specified timepoints throughout the trial. The trial aims to compare the efficacy of immediate-release dexamfetamine sulfate (DEX IR) tablets and modified-release dexamfetamine sulfate (DEX XL) capsules against placebo in adult patients with **Attention Deficit Hyperactivity Disorder (ADHD)**.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed informed consent and data protection declaration prior to initiation of any trial procedures
- Male or female adult patient ≥18 years of age at time of enrolment
- 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
- Confirmation of onset of ADHD in childhood (at the age of <12 years) using the WURS-k questionnaire for retrospective assessment
- Patient has a minimum ADHS-DC-Q total score of 32 at Screening (Visit -2)
- Patient has a minimum CGI-S score of 4 at Screening (Visit -2)
Exclusion Criteria
- A History or presence of inflammatory bowel disease (IBD); Crohn's disease in particular can lead to an altered absorption of active pharmaceutical ingredients
- 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
- 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
- History of serotonin syndrome events
- Any severe psychiatric condition that requires medication
- 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)
- 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.
- Significant hepatic, gastrointestinal, renal, haematological or oncologic disorder
- Diagnosis of current glaucoma, hyperthyroidism, pheochromocytoma or porphyria
- Diagnosis or family history of Tourette's syndrome or dystonia (Tic disorders (F95) and dystonias (G24), if they are associated with functional impairments.
- Pre-existing cerebrovascular disorders such as cerebral aneurysm, vascular abnormalities including vasculitis or stroke
- Any severe psychiatric condition that requires medication
- Immunodeficiency disorders (e.g., organ transplantation, HIV infection)
- 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
- 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
- Pregnancy and lactation
- Participation in another interventional clinical trial during the trial and within the previous 30 days prior to trial start
- Patients who are institutionalised by court order or regulatory action
- 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
- Pre-existing cardiovascular disorders including moderate and severe hypertension (systolic blood pressure ≥160 mmHg, diastolic blood pressure ≥100 mmHg), heart failure, myocardial infarction, etc.
- 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
- 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])
- Known previous non-response to dexamfetamine sulfate
- 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)
- A history of alcohol abuse or substance abuse disorder (exclusively nicotine abuse)
- Positive urine drug test at Visit -2 and, if applicable, also at Visit -1 (except for patients taking bupropion)
- Legal incapacity and/ or other circumstances rendering the patient unable to understand the nature, scope and possible impact of the clinical trial
- Known to be or suspected of being unable to comply with the clinical trial protocol
- 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
- Change of antidepressants including bupropion due to psychiatric condition within 3 months prior to Visit 0
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 04 Mar 2024 | 380 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo for test 2 - 10 mg | Placebo | N/A | — | — | — | N/A |
Placebo for test 2 - 15 mg | Placebo | N/A | — | — | — | N/A |
Placebo for test 1 - 10 mg | Placebo | N/A | — | — | — | N/A |
Placebo for Test 1 - 5 mg | Placebo | N/A | — | — | — | N/A |
Dexamfetamine sulfate 20 mg modified-release capsule | Test | MODIFIED-RELEASE CAPSULE, HARD | ORAL | 20 | 44 | PRD10988409 |
Attentin 5 mg, Tablette | Test | TABLETTE | ORAL | 20 | 44 | PRD4399724 |
Attentin 10 mg Tablette | Test | TABLETTE | ORAL | 20 | 44 | PRD4399725 |
Dexamfetamine sulfate 15 mg modified-release capsule | Test | MODIFIED-RELEASE CAPSULE, HARD | ORAL | 20 | 44 | PRD10988408 |
Placebo for test 2 - 20 mg | Placebo | N/A | — | — | — | N/A |
Dexamfetamine sulfate 10 mg modified-release capsule | Test | MODIFIED-RELEASE CAPSULE, HARD | ORAL | 20 | 44 | PRD10988407 |