In-clinic Crossover Study in Subjects With Two Treatments (Fed vs Fasted)

Exclusion Criteria

• •1. Medical History
• •1. Current and/or recurrent disease or illness that, in the opinion of an investigator, could affect the study conduct, study outcome, subject safety, or pharmacokinetic (PK) assessments (e.g., hepatic disorders, renal insufficiency, non-self-limiting gastrointestinal disorders, weight loss surgeries).
• •2. Any clinically significant history including but not limited to arterial hypertension, pulmonary arterial hypertension, myocardial infarction, peripheral vascular disease, stroke, or evidence of other cardiovascular disease or disorder, including but not limited to ECG abnormalities such as:
• •• QT interval measurement corrected for heart rate according to the Fridericia rule (QTcF) \>450 msec for males or \>470 msec for female subjects during controlled rest at screening, qualification, and Day -1,
• •• Family history of long QT syndrome,
• •• Family history of congenital QT prolongation,
• •• PR (PQ) interval shortening \<120 msec (PR \<120 msec but \>110 msec is acceptable if there is no evidence of ventricular pre-excitation),
• •• PR (PQ) interval prolongation (\>220 msec), intermittent second-degree (Wenckebach block while asleep or in deep rest is not exclusionary), or third-degree atrioventricular block,
• •• Persistent or intermittent complete bundle branch block (BBB) or intraventricular conduction delay (IVCD) with QRS \>110 msec.
• •3. Current and/or previous history of any other serious, severe or unstable psychiatric illness which in the opinion of the investigator, may require treatment (e.g. anxiety, psychosis, mood disorder, motor tics or suicidality) or make the subject unlikely to fully complete the study, and/or any condition that presents undue risk from the study medication or procedures.
• •4. Subject has had suicidal thoughts within the last 6 months as supported by the Columbia Suicide Severity Rating Scale (C-SSRS).
• •5. Positive test results for Human Immunodeficiency Virus (HIV)-1/HIV-2 antibodies, Hepatitis B surface antigen (HBsAg) or Hepatitis C virus antibody (HCVAb).
• •6. A family history of sudden cardiac or unexplained death.
• •7. Any condition or abnormal laboratory finding that could result in harm to the subject, affect the outcome of the study or suggest unstable medical illness.
• •8. Any clinically significant psychiatric disorder or finding which the Investigator considers the subject disqualified from the study.
• •9. Subject plans to undergo elective procedures/surgery at any time during the study.
• •10. Subject has had surgery within the past 90 days.
• •11. Subject of child-bearing potential is pregnant or planning to become pregnant during the duration of the study or within 30 days of the end of the study.
• •12. Subject is breast-feeding during the study or within 30 days following the study.
• •2. Medications a. Subject has taken any medication that, in the opinion of an Investigator, has been shown to alter the PK of d-MPH.
• •b. Use of any prescription medication within 14 days prior to Qualification and Day -1 and/or use of any OTC medications (such as antacids, vitamins, minerals, dietary/herbal preparations, and nutritional supplements) within 7 days prior to Qualification and Day -1, unless jointly approved by an Investigator and Sponsor. Subjects may not use these medications for the full duration of the stay at the study center until EOS.
• •i. Subjects are permitted to take hormonal contraceptives and hormone replacement therapy at acceptable levels if stable at least 30 days prior to Qualification, through the duration of the study, and for 30 days after the study ends.
• •ii. Acetaminophen (up to 2 grams per day) may be used during the study under the direction of the Investigator.
• •iii. COVID vaccine is allowed if taken at least 45 days prior to Qualification Protocol CTx-1301-013 Version 1.0 Page 25 of 49 CONFIDENTIAL iv. On a case-by-case basis, an Investigator is permitted to allow the use of certain concomitant medications, for example, to treat an AE, as long as an Investigator determines that the medication will not affect the subject's safety or study integrity (e.g., topical medications).
• •3. Alcohol/Substance Abuse
• •a. Lifetime history of alcohol or other substance abuse. b. Subject has positive urine alcohol test or urine screen for drugs of abuse at screening, qualification or check-in. (Screening visit urine MPH screen results are not required prior to Qualification day but are necessary prior to randomization on Day -1. Day-1 urine MPH screen results are not required prior to dosing in each Period).
• •4. Smoking
• •a. Subject is a current smoker or has recently discontinued smoking (i.e., regular use of any nicotinecontaining products within 3 months of screening). Occasional, social use, or routine environmental exposure to nicotine is acceptable.
• •5. Allergy/Intolerance
• •a. Subject has a history of allergy to d-MPH, to any component of the dosage form, or any other allergy, which, in the opinion of an Investigator, contraindicates their participation.
• •6. Clinical Studies
• •a. Receipt of an investigational drug within the 30 days before screening day. b. Previous participation in a CTx-1301 study.
• •7. Personnel
• •a. An employee of the sponsor, study site, or members of their immediate family.
• •8. Blood
• •1. Subject has donated blood within 56 days prior to screening, plasma within 7 days prior to screening, or experienced significant blood loss (excess of 500 mL) within 3 months prior to screening and for the duration of the study.