Fed-Fast Crossover Study to Assess the Effect of Food With CTx-1301 in Healthy Subjects

An Open-label, Randomized, Single-dose, Two-period, Two-treatment (Fed vs Fasted), Two-sequence, Crossover Study in Healthy Adult Subjects to Assess the Effect of Food on the Absorption and Bioavailability of CTx-1301 (Dexmethylphenidate)

The primary purpose of this study is to assess the effect of food on the rate and extent of absorption and the overall bioavailability of a single dose of CTx-1301 25 mg trimodal tablets in healthy adult volunteers.

An open-label, randomized, single-dose, two-sequence, two-period, in-clinic crossover study with two treatments (fed vs fasted) in approximately 26 healthy adult subjects aged 18 to 50 years.

Fed arm: Following an overnight fast of 10.5 hours, subjects should begin and finish consuming the test meal within 30 minutes, prior to administration of CTx-1301 (25 mg). CTx-1301 (25 mg) should be administered with approximately 240 mL (8 fluid ounces) of water. No food should be allowed for at least 4 hours post-dose. Water can be allowed as desired except for at least one hour before and at least one hour after drug administration. Subjects should receive standardized meals as defined in the study schedule for the fed treatment arm.

Fasted arm: Following an overnight fast of 10.5 hours, subjects should be administered CTx-1301 (25 mg) with approximately 240 mL (8 fluid ounces) of water. No food should be allowed for at least 4 hours post-dose. Water can be allowed as desired except for at least one hour before and at least one hour after drug administration. Subjects should receive standardized meals as defined in the study schedule for the fasted treatment arm.

A high-fat (approximately 50 percent of total caloric content of the meal) and high-calorie (approximately 800 to 1000 calories) meal is used as the test meal for food-effect bioanalytical (BA) and fed bioequivalency (BE) studies. This test meal allows approximately 150, 250, and 500-600 calories from protein, carbohydrate, and fat, respectively. The test meal, eaten within 30 minutes prior to administration of CTx-1301, is two eggs fried in butter, two strips of bacon, two slices of toast with butter, four ounces of hash brown potatoes and eight ounces of whole milk.

Inclusion Criteria:

1. Gender a. Male or Female

2. Age

   1. Aged between 18 and 50 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. Able to fully consume the required fed meal within 30 minutes without substitutions.
   3. If sexually active, male subjects must use an acceptable method of contraception, which includes the double-barrier method (condom and spermicide) or agree to remain abstinent from heterosexual intercourse from Day -1 (check-in), during the study, and for 90 days following the last administration of study drug.
   4. If sexually active, female subjects of child-bearing potential must use an acceptable method of contraception, which includes, hormonal contraceptives, intrauterine device (IUD) with or without hormones, or double-barrier method (e.g. condom and spermicide), or remain abstinent from heterosexual intercourse for 30 days prior to screening during the study and for 30 days following the last administration of study drug.
   5. Male subjects must agree not to donate sperm during the study and for 90 days following the last administration of study drug.
   6. 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. 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 integrity of study data.
   2. No signs of illness (fever or vomiting) within 24-hours of check-in at Day -1
   3. Subject has sufficient venous access at the time of screening to allow cannulation and/or venipuncture to obtain the required volume of blood for this study.

7. Smoking/Caffeine/Alcohol

   1. Subject must be a non-smoker (i.e., does not use any form of nicotine products) as defined by exclusion #4 in this protocol.
   2. Subject must be able to refrain from caffeine or xanthine-containing beverages or foods (e.g., tea, coffee, chocolate, cola) for 10 hours prior to check-in at Day -1 and for the duration of the study.
   3. Subject must be able to refrain from using alcohol 48 hrs. prior to Day -1 and for the duration of the study.

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. ADD/ADHD, 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. Any clinically significant psychiatric disorder or finding which the Investigator considers the subject disqualified from 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 following the study.
   12. Positive result of COVID-19 testing at Day -1.

2. Medications

   1. Subject has taken any medication that, in the opinion of an Investigator, has been shown to alter the PK of d-MPH.
   2. Use of any prescription medication within 14 days prior to 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 Day -1, unless jointly approved by an Investigator and Sponsor. Subjects may not use these medications through the full duration of the study.

   i. Subjects are permitted to take hormonal contraceptives and hormone replacement therapy at acceptable levels if stable at least 30 days prior to Day -1, 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 Day -1 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

   1. Recent history (within the last year) of alcohol or other substance abuse.
   2. Subject has positive urine alcohol test or urine screen for drugs of abuse at screening or check-in.

4. Smoking a. Subject is a current smoker or has recently discontinued smoking (i.e., regular use of any nicotine-containing products within 3 months of screening). Occasional or social use of 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 a. 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.