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

NCT ID: NCT01124708

Last Updated: 2013-09-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 134 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2011-02-28

Brief 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.

Detailed 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.

Conditions

ADHD

Keywords

ADHD; Attention Deficit Hyperactive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo

Placebo will be provided as white, opaque gelatin capsules in sham strengths of 1mg, 5mg, and 25mg

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be provided as white, opaque gelatin capsules in sham strengths of 1mg, 5mg, and 25mg

TC-5619

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, one capsule once daily p.o.

Group Type: ACTIVE_COMPARATOR

TC-5619-238

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Placebo

Placebo will be provided as white, opaque gelatin capsules in sham strengths of 1mg, 5mg, and 25mg

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Targacept Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul Newhouse, MD

Role: PRINCIPAL_INVESTIGATOR

Fletcher Allen Health Care, Dept. of Psychiatry

Locations

Florida Clinical Research Center, LLC

Bradenton, Florida, 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

Scientifc Clinical Research, Inc.

North Miami, Florida, United States

Clinical Neuroscience Solutions, Inc.

Orlando, Florida, United States

Atlanta Center For Clinical Research

Atlanta, Georgia, United States

CRI Worldwide, LLC (Lourdes Division)

Willingboro, New Jersey, United States

Neuro-Behavioral Clinical Research, Inc.

Canton, Ohio, United States

Midwest Clinical Research Center

Dayton, Ohio, United States

Oregon Center For Clinical Investigations, Inc. (OBBI, Inc.)

Portland, Oregon, United States

CRI Worldwide, LLC (Kirkbride Division)

Philadelphia, Pennsylvania, United States

Clinical Neuroscience Solutions, Inc.

Memphis, Tennessee, United States

FutureSearch Clinical Trials, LP

Austin, Texas, United States

Claghorn-Lessem Research Clinic

Houston, Texas, United States

Fletch Allen Health Care, Dept. of Psychiatry, Univ. of Vermont

Burlington, Vermont, United States

Countries

United States

Other Identifiers

PRO-05619-CRD-002

Identifier Type: -

Identifier Source: secondary_id

TC-5619-238-CRD-002

Identifier Type: -

Identifier Source: org_study_id