| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Attention-Deficit/Hyperactivity Disorder |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Behaviours [F01] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess the treatment efficacy vs placebo of repeated low doses (20 μg) of MM-120 for six weeks in adult subjects with ADHD measured by Adult Attention Deficit Investigator Symptom Rating Scale (AISRS). |
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| E.2.2 | Secondary objectives of the trial |
1. To assess treatment efficacy vs placebo measured by change from baseline in AISRS after 1 week of treatment.
2. To assess treatment efficacy vs placebo based on the proportion of subjects who experience at least a 1-point decrease in the Clinical Global Impression - Severity of Illness Scale (CGI-S).
3. To assess treatment efficacy vs placebo measured by change from baseline in CGI-S.
4. To assess the safety and tolerability by Adverse Event (AE) and Serious Adverse Event (SAE) assessment. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Ability and willingness to provide written, informed consent prior to initiation of any study-related procedures and to adhere to all study requirements.
NOTE: The subject (i.e., not a legally authorized representative) must be cognitively able to understand the requirements of the study and provide the informed consent
2. Age ≥ 18 and ≤ 65 years at Screening.
3. Subjects with the diagnosis of Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) ADHD, as determined by clinical evaluation and confirmed by structured interview (MINI).
4. AISRS total score of ≥ 26 at screening.
5. CGI-S score of ≥ 4 at screening.
6. Must be willing to receive IMP dose twice weekly. On day 1, the subject will come to the site clinic and must be willing to take a taxi or public transportation home or be accompanied by a caregiver and not drive a car, use heavy equipment, or participate in any other dangerous activity for the remainder of the day after receiving IMP
(NOTE: at any protocol visit after Day 1 dosing, dosing visits may occur at the subject’s home at the discretion of the PI, conducted by one of the study investigators or delegate and administered under supervision followed by the performance of the same procedures done at the clinic including safety monitoring. If early withdrawal is considered due to any safety issue identified, the Sponsor’s medical monitor should be notified. If a remote visit is conducted due to any reason related to the COVID-19 pandemic, notification must be sent to the Medical Monitor’s dedicated email address and Urgent Safety Measures as outlined in this protocol must be followed.)
7. Must be willing to refrain from more than 6 standard alcoholic drinks per week (1 standard drink corresponds to 0.1 L wine, 0.3 L beer, or 4 cL liquor), more than 10 cigarettes a day, and more than 2 cups of coffee a day throughout the study treatment period (6 weeks) and until the last study visit is complete (EoS or ET). |
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| E.4 | Principal exclusion criteria |
1. Past or present diagnosis of a primary psychotic disorder or first degree relative with a psychotic disorder.
2. Past or present bipolar disorder (DSM-5).
3. Other current psychiatric disorders that, in the opinion of the Investigator or medical supervisor, may confound the results of the study (e.g., obsessive-compulsive disorder, dysthymic disorder, panic disorder, dissociative disorder, anorexia nervosa or bulimia nervosa)
4. Subjects with past (> 1 month prior to the screening visit) or present history of substance use disorder (except nicotine, provided subject does not smoke more than 10 cigarettes a day).
5. Somatic disorders including Central Nervous System (CNS) involvement of cancer, severe cardiovascular disease, untreated hypertension, severe liver disease (liver enzyme increase by more than 3x the upper limit of normal except unconjugated hyperbilirubinemia due to Gilbert’s Disease, per Investigator), severely impaired renal function (estimated creatinine clearance < 50 mL/min by CKD-EPI formula), or anything else that, in the judgment of the Investigator or medical supervisor, poses too great a potential for side effects.
6. Any lifetime history of suicide attempt; or recent (within 6 months prior to the screening visit) active suicidal thoughts or ideation (defined as a suicidal ideation score of 2 or greater in the Columbia-Suicide Severity Rating Scale [C-SSRS]); or endorsement of any suicidal behavior on the C-SSRS within the past 6 months prior to the screening visit.
7. Likely to require psychiatric hospitalization during the course of the study.
8. Once consent is signed, subject not willing or safely able to stop any prescription or non-prescription ADHD medications during screening and prior to the baseline visit through final study visit, EoS or ET. A list of prohibited medications is provided in Appendix 1.
9. Plan to start, stop, or alter the use of any medications, supplements, or other therapeutics from Baseline until the EoS or ET (see Appendix 1 for list of prohibited medications).
10. Plan to start, stop or alter the use of psychotherapy, massage, meditation, acupuncture, hypnosis, yoga, or other similar therapy/activity from the time of providing informed consent until EoS or ET.
11. Use of potent CYP2D6 inhibitors; moderate CYP2D6 inhibitors by Investigator discretion (see Appendix 3).
12. Likely to need any psychiatric medications with the potential to confound interpretation of study results or impact safety, at the discretion of the Investigator, in the 10 weeks following Baseline up to EoS or ET.
13. Use of investigational medication/treatment in the past 30 days prior to the screening visit.
14. Subjects with a positive urine drug screen (with the exception of THC or metabolites) at Screening OR Baseline.
15. Clinically significant abnormal baseline laboratory, VSs, and ECG values which include the following:
o Have evidence of clinically significant hepatic disorder (e.g., alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >3X ULN (except for Gilbert’s disease).
o Any clinically significant abnormal metabolic or hematologic screen, per Investigator or medical supervisor decision.
o Exclusionary blood pressure: > 140 mm Hg (systolic) or > 90 mm Hg (diastolic); heart rate <45 beats/minute or >90 beats/minute after an approximately 5-minute supine or semi-supine rest.
NOTE: If the first measurement of a subject’s heart rate is >90 beats/minute, a second recording is allowed after an additional approximately 5-minute supine rest.
o Exclusionary ECG parameters: QTcF > 450 msec (men), QTcF >470 msec (women).
o Any clinically significant abnormal electrocardiogram (ECG) finding (e.g., uncontrolled atrial fibrillation, ischemia) at Screening (Visit 1) or Baseline (Visit 2), as determined by the Investigator or medical supervisor (in consultation with a cardiologist, if needed).
16. Any other condition, therapy, laboratory abnormality, or other circumstance that, in the opinion of the Investigator or medical supervisor, may pose additional risk to the subject from participation in the study, may interfere with the subject’s ability to comply with study procedures, may make participation in the study not in the subject’s best interest or may confound the results of the study.
17. Prior history or ongoing neuropsychiatric signs or symptoms associated with COVID-19 such as development of, or current disorder, during or after a COVID-19 infection including anxiety, memory loss, confusion, depression, delirium, agitation, or psychosis.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Mean change from baseline in ADHD symptoms, as assessed by the AISRS after 6 weeks of treatment. The AISRS total score consists of 18 items from the original Attention- Deficit/Hyperactivity Disorder - Rating Scale (ADHD-RS), which were derived based on DSM-5 criteria for ADHD. The ADHD-RS includes 9 items that address symptoms of inattention, and 9 items that address symptoms of impulsivity and hyperactivity. Each item is rated from 0 to 3. The AISRS total score can range from 0 to 54. A higher score corresponds to a worse severity of ADHD. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| This end point will be evaluated after 6 weeks of dosing (12 administrations) |
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| E.5.2 | Secondary end point(s) |
ADHD-related endpoints
key secondary endpoint: change from baseline in AISRS after 1 week (2 doses) of treatment.
occurrence of patients who experience at least a 1-point decrease in the CGI-S
change from baseline in CGI-S after 1 week (2 doses) of treatment and after 6 weeks of treatment
change from baseline in patient self-assessment by the Adult ADHD Self-Report Scale (ASRS) and Connors’ Adult ADHD
Rating Scale (CAARS).
Safety Endpoints
● Vital signs (supine blood pressure, heart rate)
● 12-lead safety ECG
● Adverse events (e.g., psychological and/or physiological adverse
events)
● Columbia-Suicide Severity Rating Scale (C-SSRS)
● Safety laboratory evaluation and Urine pregnancy testing |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| This end point will be evaluated after 6 weeks of dosing (12 administrations) |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
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