P3b Short-term Study of CTN in Patients With ADHD and Comorbid Anxiety

Inclusion criteria

• Participants between 18 and 65 years of age, inclusive.
• Diagnosis of ADHD per the DSM-5-TR criteria and confirmed using the ACDS Version 1.2 at screening.
• AISRS total score of ≥ 28 at baseline.
• Diagnosis of GAD and/or SAD per DSM-5-TR criteria and confirmed using the MINI at screening.
• HAM-A total score ≥ 20 at baseline.
• CGI-S-ADHD and CGI-S-anxiety rating ≥ 4 at baseline.
• Body mass index from 18.0 to 40.0 kg/m2 (inclusive).
• Ability to provide written, informed consent prior to initiation of any trial-related procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the trial.

Exclusion criteria

• In the clinical opinion of the investigator, participant has not derived therapeutic benefit from 2 or more ADHD therapies of 2 different classes (eg, amphetamine and methylphenidate, or amphetamine and atomoxetine) given with an acceptable dose and duration during adulthood (aged 18 years or older).
• In the clinical opinion of the investigator, participant has not derived therapeutic benefit from 2 or more anxiety therapies of 2 different classes (eg, selegiline and duloxetine, or buspirone and lorazepam) given with an acceptable dose and duration during adulthood (aged 18 years or older).
• Current use of prohibited psychotropic medications that cannot be discontinued 2 weeks prior to randomization. Fluoxetine is prohibited within 28 days of randomization.
• Participants who have started individual or group psychotherapy within the past 3 months prior to screening (ongoing psychotherapy that is not expected to change in frequency or type during the trial is permissible).
• Any disorder that is the primary focus of treatment other than ADHD.
• Participants with lifetime DSM-5-TR diagnosis of neurocognitive disorder, schizophrenia or any psychotic disorder, bipolar disorder, autism spectrum disorder, or personality disorders. Participants with current diagnosis of post-traumatic stress disorder, obsessive compulsive disorder, any substance use disorder, eating disorders, major depressive disorder; or other anxiety disorders such as panic disorder, agoraphobia, separation anxiety disorder, selective mutism, substance or medication induced anxiety, or due to medical condition, or specific phobia will be excluded.
• Participant is, in the investigator's judgment, at significant risk for suicide. A participant with a Columbia-Suicide Severity Rating Scale (C-SSRS) ideation score of 4 or 5 within the last 6 months or participants who answer "Yes" on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) within the past year must be excluded.
• Participants with a positive UDS for illicit drugs at screening or baseline. Participants with a positive drug test at screening for ADHD or anxiety medications including methylphenidate, or amphetamines, may continue while undergoing the required washout. Participants with a positive drug test at baseline for ADHD or anxiety medications are excluded. A positive drug test at baseline for drugs of abuse, including cannabis, unless all of the following cannabis specific conditions are met:

• No DSM-5-TR diagnosis of cannabis use disorder within the past 12 months;
• If per investigator's judgement, cannabis use will not compromise safety, efficacy assessments or protocol compliance.
• Participant agrees to maintain their consistent use pattern throughout the trial
• Participant agrees to refrain from cannabis use within 12 hours of trial visits.
• Participants with evidence of current substance use disorder or history in the past 12 months.
• Participants with epilepsy, a history of epilepsy, or a history of seizure, except for a single childhood febrile seizure, a single seizure post brain injury, or a single seizure due to alcohol withdrawal.
• Participants who are partially hospitalized or receiving inpatient care or have any other medical or physical condition(s) that, in the opinion of the investigator, may prevent the participant from completing the trial or would go against the participant's best interest with participation in the trial. This would include any significant illness or unstable medical condition that could lead to difficulty complying with the protocol. This would also include most bariatric surgeries, with the only exception being those where there has been no breach of the gastrointestinal wall (ie, uncomplicated lap band surgery) AND no sign of malabsorption.
• The following laboratory test and ECG results are exclusionary at screening:

• Platelets ≤ 75,000/mm3
• Hemoglobin ≤ 9 g/dL
• Neutrophils, absolute ≤ 1000/mm3
• AST > 2 × upper limit of normal
• ALT > 2 × upper limit of normal
• Creatinine ≥ 2 mg/dL
• HbA1c ≥ 7%
• QTcF ≥ 450 msec for males or ≥ 470 msec for females
• Abnormal free thyroxin (T4), unless discussed with and approved by the medical monitor (Note: free T4 is measured only if result for thyroid stimulating hormone [TSH] is abnormal)
• Participants presenting with, or having a history of, uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure > 95 mmHg) or symptomatic hypotension, or orthostatic hypotension which is defined as a decrease of ≥ 30 mmHg in systolic blood pressure or a decrease of ≥ 20 mmHg in diastolic blood pressure after at least 3 minutes standing compared with the previous supine blood pressure, or development of symptoms.
• Participants with a history of any prior exposure to centanafadine.
• Participants who have participated in other clinical trials involving investigational drugs within 180 days prior to screening or who have participated in more than 2 interventional clinical trials involving investigational drugs within the past year.
• Participants of childbearing potential who are breast-feeding and/or have a positive pregnancy test result prior to receiving IMP.
• Participants of reproductive potential / POCBP who do not agree to practice 2 different effective and/or highly effective methods of birth control or remain fully abstinent from sexual activity with the potential for conception, per the guidelines in Section 10.3.
• Participants who do not agree to refrain from donating sperm or eggs from trial screening through 90 days for sperm and 30 days for eggs after the last dose of IMP.
• Participants who have an allergy to the IMP or any component of the IMP.