CTx-1301 Comparative Bioavailability Study

The primary purpose of this study is to compare the bioavailability of CTx-1301 (dexmethylphenidate) to the registered listed drug, Focalin XR and to evaluate dose proportionality of CTx-1301. In addition, this study seeks to characterize the pharmacokinetics of dexmethylphenidate and evaluate the safety and tolerability of CTx-1301.

The study will comprise of a randomized, single-dose, four-sequence, four-period, in-clinic crossover study in approximately 36 adult ADHD subjects. All subjects considered eligible at Screening will proceed to tolerability test day, dosing 40 mg Focalin XR to evaluate safety and tolerability of the higher dose of d-MPH. If subject is able to safely tolerate the test dose, and meets all inclusion/exclusion criteria, they will be considered eligible for randomization into the study. All subjects will be randomized to receive four treatments throughout the course of the study; one CTx-1301 trimodal d-MPH tablet containing 6.25 mg d-MPH, one Focalin 5 mg XR capsule, one CTx-1301 50 mg tablet, and one 40 mg Focalin XR capsule. Administration of study drug will occur only on Assessment Days; no study drug will be administered during screening or unscheduled days (USVs).

The lowest and highest doses of CTx-1301 (dexmethylphenidate, 6.25 and 50 mg) were selected to bridge to the lowest and highest doses of Focalin XR (dexmethylphenidate, 5 and 40 mg) in this comparative BA study.

Eligibility Criteria:
Inclusion Criteria:

1. Gender

   a. Male or Female
2. Age

   a. Aged between 18 and 55 years inclusive.
3. Weight and BMI

   1. Body weight ≥ 50 kg
   2. BMI ≥ 18 and ≤ 35
4. Compliance

   1. Understands and is willing, able and likely to comply with all study procedures and restrictions.
   2. If sexually active, male subjects must use the double-barrier method (condom and spermicide) for birth control during the study and for 90 days following the last administration of study drug.
   3. If sexually active, female subjects of child-bearing potential must use an acceptable method of contraception, including abstinence from heterosexual intercourse, hormonal contraceptives, intrauterine device (IUD) with or without hormones, or double-barrier method (e.g. condom and spermicide), during the study and for 30 days following the last administration of study drug.
   4. Male subjects must agree not to donate sperm during the study and for 90 days following the last administration of study drug.
   5. Female subjects must agree not to donate eggs during the study and for 30 days following the last administration of study drug.
5. Consent a. Demonstrates understanding of the study and willingness to participate as evidenced by voluntary written informed consent (signed and dated) obtained before any study-related activities are performed.
6. Indication

   1. Subject must report history of diagnosis of ADHD.
   2. If subject is currently taking stimulant medication, they must be willing and able to safely abstain from any other ADHD treatment during 96 hrs. prior to check-in on Day -4 and through the complete duration of the study.
7. General Health

   1. Good general health (in the opinion of an investigator) with no clinically significant or relevant abnormalities on medical history or physical examination which could affect the safety of the subject or study data.
   2. No vomiting or fever within 24-hours of check-in at Day -4
   3. Subject has sufficient venous access to allow cannulation and/or venipuncture to obtain the required volume of blood for this study.
   4. Subject must currently be taking or previously have taken a stimulant medication for ADHD.
8. Smoking/Caffeine/Alcohol

   1. Subject must be able to refrain from smoking cigarettes 1 hour prior to dosing and 7 hours after dosing on dosing days. Subject must agree not to smoke more than one cigarette per hour, not to exceed 10 cigarettes per day.
   2. Subject must be able to refrain from caffeine for 10 hours prior to check-in at Day -4 and for the duration of the study.
   3. Subject must be able to refrain from using alcohol 48 hrs. prior to Day -4 and for the duration of the study.
9. ADHD Medication History

   1. Subject's medication history suggests they will be able to tolerate a 40 mg dose of dexmethylphenidate.
   2. Subject must demonstrate tolerability of dexmethylphenidate assessed by tolerability day/test dose of 40 mg Focalin XR as evaluated by the investigator.

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, congestive heart failure).
   2. 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.
   3. Subject cannot have suicidal thoughts within the last 6 months as supported by the Columbia Suicide Severity Rating Scale (C-SSRS).
   4. Positive test results for Human Immunodeficiency Virus (HIV)-1/HIV-2 antibodies, Hepatitis B surface antigen (HBsAg) or Hepatitis C virus antibody (HCVAb).
   5. A family history of sudden cardiac or unexplained death.
   6. 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.
   7. As a result of the MINI, medical history, physical examination, and/or screening investigations (including ECG results, vital signs and/or laboratory abnormality), an Investigator considers the subject disqualified for the study.
   8. Subject plans to undergo elective procedures/surgery at any time during the study.
   9. Subject has had surgery within the past 90 days.
   10. 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.
   11. Subject is breast-feeding during the study or within 30 days of 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 Day -3 (ADHD medications must be discontinued at least 96 hours prior to check-in at Day -4), and/or use of any OTC medications (such as antacids, vitamins, minerals, dietary/herbal preparations, and nutritional supplements) within 7 days prior to Day -3 unless jointly approved by an Investigator and Sponsor.

   i. Subjects are permitted to take hormonal contraceptives and hormone replacement therapy at acceptable levels if stable at least 30 days prior to Day -4, 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. 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 (eg, topical medications).
3. Alcohol/Substance Abuse

   1. Recent history (within the last year) of alcohol or other substance abuse.
   2. Subject has positive breath alcohol test or urine test for drugs of abuse at screening or check-in (prescribed ADHD medication is acceptable during screening but must be stopped at least 96 hrs prior to check in at Day -4). Note: At the discretion of an Investigator, the tests may be repeated. If THC is positive at screening or check-in, a cannabis intoxication evaluation will be done by an investigator at check-in only; inclusion will be at the investigator's discretion, due to the slow release of THC from adipose tissue.
4. Smoking

   a. Subject regularly smokes more than 10 cigarettes/day (or other nicotine-containing products) or Subject has recently discontinued smoking (within the last 3 months)
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

   1. Participation in another investigational product study (inclusive of final post-study examination) or receipt of an investigational drug within the 30 days before screening day.
   2. Previous participation in this study.
7. Personnel

   a. An employee of the sponsor, study site, or members of their immediate family.
8. Blood

   1. Subject has donated blood, plasma, or experienced significant blood loss (excess of 500 ml) within 3 months of screening and for the duration of the study.