CX717 in the Treatment of Adult ADHD

Phase 2

Completed

• Conditions: Attention Deficit Hyperactivity Disorder
• Interventions: Drug: CX717 200 mg; Drug: CX717 800 mg; Drug: Placebo

• Registration Number: NCT03375021
• Lead Sponsor: RespireRx

Brief Summary

A Randomized, Double-Blind, Two-Period Crossover Study to Assess the Efficacy And Safety of the Ampakine® Compound, CX717, versus Placebo in Adults with Attention-Deficit Hyperactivity Disorder

Detailed Description

This study examined the clinical efficacy, tolerability and safety of CX717 in the treatment of adults with ADHD. The study was a double-blind, 2-period crossover study that compared 2 different doses of CX717 with placebo. Subjects were randomized to 1 of 4 different treatment sequences: placebo - low dose; low dose - placebo; placebo - high dose; or high dose - placebo. Each treatment period was 3 weeks with a 2-week washout between treatment periods. The doses chosen were 200 mg b.i.d. and 800 mg b.i.d.

Study Timeline

• Study Start: 2005-07-19
• Primary Completion: 2006-01-10
• Study Completion: 2006-01-10
• Status Verified: 2017-12
• Study First Submitted: 2017-12-07
• Study First Submitted QC: 2017-12-14
• Last Update Submitted: 2017-12-14
• Study First Posted: 2017-12-15
• Last Update Posted: 2017-12-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 68

Inclusion Criteria

1. Subject had ADHD as established by the Adult ADHD Clinical Diagnostic Scale (ACDS) Version 1.2

2. Patients must have at least moderately severe ADHD symptoms:

   • Subject had an ADHD-RS score of ≥22
   • Subject had a CGI-S score of ≥4

3. Subject was male

4. Subject was 18 - 50 years old, inclusive

5. Subject could read well enough to understand the informed consent form and other patient materials.

Exclusion Criteria

1. Subject had a DSM-IV diagnosis of ADHD not otherwise specified

2. Subject had a current or lifetime history of bipolar disorder or any psychotic disorder as established by the Structured Clinical Interview for DSM-IV (SCID) (12)

3. Subject had a current history of major depression, substance abuse or dependence, generalized anxiety disorder, obsessive compulsive disorder, panic disorder, or posttraumatic stress disorder as established by SCID

4. Subject had a history of epilepsy, seizures, syncope, unexplained blackout spell(s), head trauma with loss of consciousness, or febrile seizures

5. Subject had a currently active medical condition (other than ADHD) that in the opinion of the Investigator could interfere with the ability of subject to participate in the study

6. Subject had a history of development delay in milestones

7. By history, the subject had an IQ less than 80

8. In the opinion of the Investigator, the subject had not derived significant therapeutic benefit from 2 or more appropriately dosed ADHD therapies

9. Subject was currently taking medication specifically for treatment of ADHD symptoms (e.g., stimulants, atomoxetine, tricyclic antidepressants, or bupropion).

   NOTE: subjects were off of stimulants for 2 weeks and off non-stimulant ADHD therapies for 4 weeks prior to the Period 1 Baseline Visit. Subject did not have evidence of a discontinuation or withdrawal reaction.

10. Subject was currently taking an anti-depressant prescription medication (e.g., paroxetine, sertraline, venlafaxine, etc.) or St. John's Wort

11. Subject was currently taking an anti-convulsant medication (e.g., phenytoin, carbamazepine, lamotrigine, valproic acid, etc.) or anti-psychotic medication

12. Subject had a clinically relevant abnormality on Screening evaluation including physical examination, vital signs, ECG, or laboratory tests

13. Subject was currently taking on a chronic basis any medication known to be primarily metabolized by a route other than the cytochrome P450 system

14. Subject was unwilling to refrain from taking medications that may have interfered with the assessment of cognitive function. Examples included benzodiazepines, sedating anti-histamines, zolpidem, and zaleplon. Herbal preparations with effects on the central nervous system (e.g., St. John's Wort, melatonin) were prohibited. These medications and herbal preparations were also prohibited throughout the study.

15. Subject was unwilling to refrain from taking more than 1 unit of alcohol within 24 hours of the clinic visits

16. Subject had a Body Mass Index (BMI) of less than 18 or greater than 35. No waivers were allowed.

17. Subject reported passive or active suicidal ideation or intent

18. Subject was concurrently participating in another clinical research study or investigational drug trial or had participated within the past 1 month

19. Subject was at high risk of non-compliance in the Investigator's opinion

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sequence 1 PL	CX717 200 mg	Eligible subjects were randomized to Sequence 1 PL in which they received placebo (P) followed by crossover to CX717 200 mg low dose (L) of active treatment
Sequence 1 PL	Placebo	Eligible subjects were randomized to Sequence 1 PL in which they received placebo (P) followed by crossover to CX717 200 mg low dose (L) of active treatment
Sequence 2 PH	CX717 800 mg	Eligible subjects were randomized to Sequence 2 PH in which they received placebo (P) followed by crossover to CX717 800 mg High dose (H) of active treatment
Sequence 3 LP	CX717 200 mg	Eligible subjects were randomized to Sequence 3 LP in which they received CX717 200 mg Low dose (L) of active treatment followed by crossover to placebo (P)
Sequence 3 LP	Placebo	Eligible subjects were randomized to Sequence 3 LP in which they received CX717 200 mg Low dose (L) of active treatment followed by crossover to placebo (P)
Sequence 4 HP	CX717 800 mg	Eligible subjects were randomized to Sequence 2 PH in which they received CX717 800 mg High dose (H) of active treatment followed by crossover to placebo (P)
Sequence 4 HP	Placebo	Eligible subjects were randomized to Sequence 2 PH in which they received CX717 800 mg High dose (H) of active treatment followed by crossover to placebo (P)
Sequence 2 PH	Placebo	Eligible subjects were randomized to Sequence 2 PH in which they received placebo (P) followed by crossover to CX717 800 mg High dose (H) of active treatment

Primary Outcome Measures

Name	Time	Method
ADHD-RS	3 Weeks	Attention-Deficit Hyperactivity Disorder Rating Scale (ADHD-RS) with Prompts The ADHD-RS is an 18-item scale that assesses the severity ADHD symptoms based on the symptom list in the DSM-IV. It is administered by a qualified health care professional.; Each item is rated 0 - 3 (0=not present and 3=severe). Thus the scale has a range from 0 to 54.

Secondary Outcome Measures

Name	Time	Method
ESS	3 Weeks	Eppworth Sleepiness Scale
SCWT	3 Weeks	Stroop Color and Word Test
ADHD-RS subscales	3 Weeks	Attention Deficit Hyperactivity Disorder Rating Subscales: hyperactivity consisting of items 1-4, 8-10, 17-18, and inattentiveness consisting of items 5-7 and 11-16.
CGI-I	3 Weeks	Clinical Global Impression of Improvement
HAM-A	3 Weeks	Hamilton Rating Scale of Anxiety
PSQI	3 Weeks	Pittsburgh Sleep Quality Index
HAM-D	3 Weeks	Hamilton Rating Scale of Depression
ADHD-SRS	3 Weeks	Attention Deficit Hyperactivity Disorder Self Rating Scale
CTMT	3 Weeks	Comprehensive Trail Making Test
CPT	3 Weeks	Continuous Performance Task
FBDS	3 Weeks	Forward and Backward Digit Span