Efficacy, Safety, and Tolerability of TC-5619 in Adults With Attention Deficit/Hyperactivity Disorder (ADHD)

ADHD Clinical Trial

Official title:

A Double-blind, Randomized, Placebo-controlled, Multicenter, Fixed Dose Titration Study to Assess Efficacy, Safety, and Tolerability of TC-5619 in Adults With Attention Deficit/Hyperactivity Disorder (ADHD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01124708
• Other study ID #: TC-5619-238-CRD-002
• Secondary ID: PRO-05619-CRD-00
• Status: Completed
• Phase: Phase 2
• First received: May 5, 2010
• Last updated: September 3, 2013
• Start date: May 2010
• Est. completion date: February 2011

Study information

• Verified date: October 2011
• Source: Targacept Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

ADHD has been associated with persistent deficits in the efficient allocation of attention and supports the notion that regulation of the cholinergic system may improve these cognitive deficits in ADHD. It has been suggested that the effects of nicotine are most pronounced on tasks that demand effortful processing (Rusted and Warburton 1994). In addition, a recent theory proposes that the cholinergic system allocates additional attentional resources during tasks that are demanding (i.e. sustained attention, set shifting, etc; Sarter and Bruno 1997). Thus it may be that in ADHD, cholinergic systems are under-responsive or under-developed and thus stimulation of nicotinic receptors via nicotinic agents may result in improved cognitive performance particularly on tests requiring effortful processing.

Description:

A randomized, parallel, forced-titration design is being used to assess effects of TC-5619 versus placebo on efficacy. A parallel group design allows the effects of TC-5619 to be clearly established, and the randomized nature of the design allows minimization of observer and subject bias. Because a forced dose up-titration design will be used, effects of individual doses will be preliminary, because the design confounds dose with time.

The doses chosen (1mg, 5mg, and 25mg) reflect an appropriate range around the anticipated efficacious dose (3-10 mg), based upon preclinical extrapolations to the human, and upon the pro-cognitive effects of TC-5619 identified by CDR in the MRD study (Targacept Study TC-5619-238-CLP-002).

All subjects will be tobacco non-users. It is possible that tobacco (nicotine) interferes with α7 NNR-mediated effects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 134
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Diagnosis of ADHD per DSM-IV TR criteria

2. Score > 2 on at least 6 of 9 items in at least 1 subscale of the CAARS-INV

3. Score > 4 (at least moderate) on the Clinical Global Impression-Severity (CGI-S) index

4. Age 18 - 65, male or female

5. Tobacco non-users as indicated by lack of tobacco use within the last year prior to Screening, and by negative urinary cotinine level of < 50ng/mL after quantification

6. Able to understand and sign informed consent

Exclusion Criteria:

1. Current DSM-IV Axis I psychiatric disorder other than ADHD; use of MINI to exclude other major DSM-IV TR psychiatric diagnoses

2. Known or suspected drug abuse within the last 12 months prior to Screening

3. Urine drug screen positive for illegal or non-prescribed drugs at Screening

4. Patients at imminent risk of suicide or of danger to themselves or others

5. Use of drugs affecting cognitive function within 3 weeks prior to Day 1, including use of any medications for treatment of ADHD. Any medication wash-outs must be completed during the 3 weeks between Screening and Day 1.

6. Any other restricted or prohibited drugs.

7. Other concomitant medications that have been changed within 4 weeks prior to Screening

8. Unable to comply with study procedures in opinion of investigator, including CogState ADHD test battery

9. History of significant other major or unstable neurological, metabolic, hepatic, renal, hematological, pulmonary, CV, GI, or urological disorder; or diagnosis of major depressive disorder

10. Myocardial infarction within past year

11. Seizure disorder within past year

12. Type 1 diabetes mellitus (DM); type 2 DM that requires medication (diet-controlled allowed)

13. HbA1C > 7.4 at Screening

14. BMI < 15 or > 35; male weight < 100 lbs; female weight < 80 lbs.

15. Current TB or known systemic infection (HBV, HCV, HIV)

16. Clinically significant finding on physical exam

17. Clinically significant lab or ECG abnormality that could be a safety issue in the study, including QTcF > 450 (males) or QTcF > 480msec (females), and excluding LFTs > 1.5 times upper limits of normal

18. Women of child-bearing potential and men unwilling or unable to use accepted methods of birth control

19. Women with a positive pregnancy test, or who are lactating

20. Participation in another clinical trial in last 3 months prior to Screening

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• ADHD
• Attention Deficit Disorder with Hyperactivity

Intervention

Drug:
• TC-5619-238
TC-5619-238 will be provided as white, opaque gelatin capsules in strengths of 1mg, 5mg, and 25mg (as free base). Subjects will take 1mg TC-5619, 5mg TC-5619, 25mg TC-5619, or matching placebo - one capsule once daily p.o.
• Placebo
Placebo will be provided as white, opaque gelatin capsules in sham strengths of 1mg, 5mg, and 25mg

Locations

Country	Name	City	State
United States	Atlanta Center For Clinical Research	Atlanta	Georgia
United States	FutureSearch Clinical Trials, LP	Austin	Texas
United States	Florida Clinical Research Center, LLC	Bradenton	Florida
United States	Fletch Allen Health Care, Dept. of Psychiatry, Univ. of Vermont	Burlington	Vermont
United States	Neuro-Behavioral Clinical Research, Inc.	Canton	Ohio
United States	Midwest Clinical Research Center	Dayton	Ohio
United States	Claghorn-Lessem Research Clinic	Houston	Texas
United States	Clinical Neuroscience Solutions, Inc.	Jacksonville	Florida
United States	Fidelity Clinical Research, Inc	Lauderhill	Florida
United States	Florida Clinical Research Center, LLC	Maitland	Florida
United States	Clinical Neuroscience Solutions, Inc.	Memphis	Tennessee
United States	Scientifc Clinical Research, Inc.	North Miami	Florida
United States	Clinical Neuroscience Solutions, Inc.	Orlando	Florida
United States	CRI Worldwide, LLC (Kirkbride Division)	Philadelphia	Pennsylvania
United States	Oregon Center For Clinical Investigations, Inc. (OBBI, Inc.)	Portland	Oregon
United States	CRI Worldwide, LLC (Lourdes Division)	Willingboro	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Targacept Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CAARS-INV ADHD-rating scale	•Clinician-administered ADHD-rating scale (CAARS-INV) and is the total of 3 subscales: Inattention, Hyperactivity-Impulsivity, and ADHD Index [ Time Frame: Week -3, Day 1, Week 1, Week 4 (evaluation of 1mg dose); Week 8 (evaluation of 5mg Dose); and Week 12 (evaluation of 25mg dose)]	Week 12	No
Secondary	CAARS-INV subscales	CAARS-INV subscales: Inattention, Hyperactivity-Impulsivity, and ADHD Index, obtained [Time frame: Week -3, Day 1, Week 1, Week 4, Week 8, Week 12,Early Withdrawal (EW)]	Week 12	No
Secondary	CogState ADHD Battery	CogState ADHD test battery [Time frame: Week -3, Day 1, Week 1, Week 4, Week 8, Week 12,Early Withdrawal (EW)]	Week 12	No
Secondary	CogState Stop-Signal Task scores	CogState Stop-Signal Task scores [Time frame: Week -3, Day 1, Week 1, Week 4, Week 8, Week 12,Early Withdrawal (EW)]	Week 12	No
Secondary	CAARS-Self Rating (CAARS-S) total score	CAARS-S total score [Time frame: Week -3, Day 1, Week 1, Week 4, Week 8, Week 12,Early Withdrawal (EW)]	Week 12	No