Clinical trial NCT02547428 (phase 2, status: completed)
Conditions: attention-deficit hyperactivity disorder
ICD codes: F90.2, F90.8, F90.9, F90.0, F90.1
Drugs: ctn sr, placebo
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility 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