Safety and Efficacy Study of Centanafadine Sustained-Release (CTN SR) in Adults With Attention-Deficit Hyperactivity Disorder (ADHD)

• Status: Completed
• Trial end date: 2016-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase IIb, randomized, double-blind, multicenter, 2-period, 2-treatment, crossover study to evaluate safety, efficacy, and duration of efficacy of CTN SR BID target total daily dose (TDD) 400 mg compared with placebo in adults with ADHD.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Neurovance, Inc.; Otsuka Pharmaceutical Development & Commercialization, Inc.

Criteria

Inclusion Criteria:

1. Participant is 18 to 60 years of age, inclusive, at the time of consent

2. Participant meets Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for a primary diagnosis of ADHD, any presentation, established by a comprehensive psychiatric evaluation based on DSM-5 criteria with at least 5 of the 9 subtype criteria met, as determined by the Conners' Adult ADHD Diagnostic Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (CAADID Part II)

3. Participant has a Baseline score of greater than or equal to 28 using the ADHD-RS-IV

4. Participant has a minimum score of 4 on the CGI-S at Baseline

5. Participant is functioning at an age-appropriate level intellectually, as judged by the Investigator

Exclusion Criteria:

1. Participant has a current comorbid psychiatric disorder that is either controlled with medications prohibited in this study or is uncontrolled and associated with significant symptoms. Exclusionary conditions include any severe comorbid Axis II disorder or severe Axis I disorder (such as post-traumatic stress disorder [PTSD], psychosis, bipolar illness, severe obsessive compulsive disorder, severe depressive or severe anxiety disorder) or other symptomatic manifestations that, in the opinion of the examining physician, will contraindicate CTN SR treatment or confound efficacy or safety assessments. Specifically, participants with mild to moderate forms of Axis I disorders (e.g., social phobia and dysthymia) may be included, whereas participants with a lifetime history of psychosis or bipolar disorder will be excluded. Comorbid psychiatric diagnosis will be established by a Semi-Structured Clinical Interview for DSM-5 Axis I Disorders (the Mini lnternational Neuropsychiatric lnterview, Version 6.0 [M.I.N.I. 6.0]).

2. Participants who are currently considered a suicide risk, any participant who had previously made a suicide attempt, or those who are currently demonstrating active suicidal ideation as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening, or if in the opinion of the investigator the participant is considered a suicide risk. Participants who develop suicidal ideation or behavior during the trial as measured by the C-SSRS will be discontinued and followed appropriately.

3. The participant has a body mass index (BMI) of less than 18.5 or greater than or equal to 40 at Baseline

4. Participant has a concurrent chronic or acute illness (such as severe allergic rhinitis or an infectious process requiring antibiotics), disability, or other condition that might confound the results of safety assessments administered in the study or that might increase risk to the participant

5. Participant had a history of seizures (other than infantile febrile seizures), any tic disorder (except transient tic disorder and participant has no episodes greater than or equal to 1 year), or a current diagnosis and/or a known family history of Tourette's Disorder (i.e. first degree relatives)

6. Participant has a known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, transient ischemic attack or stroke or other serious cardiac problems that may place them at increased vulnerability to potential sympathomimetic effects

7. Participant has a known family history of sudden cardiac death or ventricular arrhythmia

8. Participant has a history of significant bleeding or coagulation disorder and/or low platelet levels (less than 130 X 109/L) or increased international normalized ratio (INR) (greater than 1.3) at Screening

9. Participant has a history of cancer

10. Participant has any clinically significant 12-lead ECG or clinically significant laboratory abnormality at Screening and/or Baseline

11. Participant has current abnormal thyroid function, as defined as abnormal Screening thyroid stimulating hormone (less than 0.34 or greater than 5.6 μIU/mL). Treatment with a stable dose of thyroid medication for at least 3 months is permitted.

12. Participant has a resting sitting systolic blood pressure (SBP) greater than or equal to 140 mm Hg or diastolic blood pressure (DBP) greater than or equal to 90 mm Hg. No more than 1 repeat measurement will be permitted.

13. Participant has a history of hyponatremia

14. Participant is on an antihypertensive medication of any kind

15. Participant has a known history of orthostatic hypotension or has an orthostatic blood pressure drop of greater than or equal to 20 mm Hg (based on the drop between sitting and standing [3 minutes] SBP) at Screening or Baseline

16. Participant has a known history of hypertension

17. Participant exhibits lifestyle that may be confounding to safety or efficacy assessments per the judgment of the investigator (e.g. exercises, diets or travels extensively)

18. Participant has a known history of glaucoma

19. Participant has failed to respond to 1 or more adequate courses (e.g., adequate dose and duration with poor response as judged by the Investigator) of stimulant therapy

20. Participant has a recent history (within the past 6 months) of suspected substance abuse or dependence disorder (excluding nicotine) in accordance with DSM-5 criteria

21. Participant is taking other medications that have central nervous system (CNS) effects or affect performance, such as sedating antihistamines and decongestant sympathomimetic, or was recently on monoamine oxidase inhibitors (during or within 14 days of investigational product [IP] administration). Stable use of bronchodilator inhalers is not exclusionary. This also includes use of any psychoactive prescription medication within 30 days prior to Screening or psychoactive over-the-counter (OTC) medication or herbal products that require more than a 7-day washout. Participants currently treated with methylphenidate or amphetamine products are permitted and will undergo a 7-day washout period. Participants who have taken atomoxetine will be required to undergo a 30-day washout.

22. Participant requires the frequent or regular use of aspirin, ibuprofen, and naproxen sodium, or is on any anticoagulant, such as warfarin

23. Participants taking known potent inhibitors or inducers of common cytochrome P450 (CYP) enzymes, including herbal products

24. Participant has a positive urine drug screen (UDS) result at Screening or Baseline. NOTE: The UDS must be negative at Screening (with the exception of the participant's current ADHD psychostimulant, if applicable) or Baseline, if applicable, for the participant to potentially be eligible for study participation. The Investigator, in conjunction with the Medical Monitor, will evaluate the potential impact of a positive UDS regarding the continued participation of the participant.

25. Participant has taken an investigational product or taken part in a clinical study within 30 days prior to Screening

26. Investigational site personnel are not permitted to participate in the study

27. Participant has participated previously in a CTN investigational study

28. The female participant is pregnant or lactating

29. Participant has a documented allergy, hypersensitivity, or intolerance to CTN or to any excipients in the reference product

30. Participant has a history of allergy or hypersensitivity to medications (e.g., monoamine reuptake inhibitors or antibiotics)

31. Participant does not agree to or is unable to abstain from consuming alcohol during the study

Reproductive Potential Requirements

32. All female participants are required to have a negative serum beta human chorionic gonadotropin (HCG) pregnancy test at Screening, a negative urine pregnancy test at Baseline, and be either postmenopausal (12 consecutive months of spontaneous amenorrhea and greater than or equal to 51 years of age), surgically sterile and at least 6 weeks poststerilization or, for females of childbearing potential, have a negative pregnancy test prior to entering the study and agree to use acceptable methods of contraception

Contraceptive Requirements

33. Condoms are to be used with all forms of contraception (i.e., double-barrier method). Acceptable contraceptives include the following:

1. Intrauterine devices

2. Hormonal contraceptives (oral, depot, patch, injectable, or vaginal ring)

3. Diaphragms with spermicidal gel or foam

34. Females of childbearing potential will be advised to use acceptable contraceptives from the date of informed consent throughout the study period and for the defined follow-up period

35. If hormonal contraceptives are used, they are to be administered according to the package insert

36. Females of childbearing potential who are not currently sexually active agree to use acceptable contraception, as defined above, if they became sexually active during their study participation and for the defined follow-up time period