Efficacy, Safety, and Tolerability of TC-5619 in Adults With Attention Deficit/Hyperactivity Disorder (ADHD)
This study has been completed.
Sponsor:
Targacept Inc.
Information provided by (Responsible Party):
Targacept Inc.
ClinicalTrials.gov Identifier:
NCT01124708
First received: May 5, 2010
Last updated: October 28, 2011
Last verified: October 2011
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
ADHD |
Drug: TC-5619-238 Drug: Placebo |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| 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) |
Resource links provided by NLM:
Further study details as provided by Targacept Inc.:
Primary Outcome Measures:
- CAARS-INV ADHD-rating scale [ Time Frame: Week 12 ] [ Designated as safety issue: No ]•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)]
Secondary Outcome Measures:
- CAARS-INV subscales [ Time Frame: Week 12 ] [ Designated as safety issue: No ]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)]
- CogState ADHD Battery [ Time Frame: Week 12 ] [ Designated as safety issue: No ]CogState ADHD test battery [Time frame: Week -3, Day 1, Week 1, Week 4, Week 8, Week 12,Early Withdrawal (EW)]
- CogState Stop-Signal Task scores [ Time Frame: Week 12 ] [ Designated as safety issue: No ]CogState Stop-Signal Task scores [Time frame: Week -3, Day 1, Week 1, Week 4, Week 8, Week 12,Early Withdrawal (EW)]
- CAARS-Self Rating (CAARS-S) total score [ Time Frame: Week 12 ] [ Designated as safety issue: No ]CAARS-S total score [Time frame: Week -3, Day 1, Week 1, Week 4, Week 8, Week 12,Early Withdrawal (EW)]
| Enrollment: | 134 |
| Study Start Date: | May 2010 |
| Study Completion Date: | February 2011 |
| Primary Completion Date: | February 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Placebo Comparator: Placebo
Placebo will be provided as white, opaque gelatin capsules in sham strengths of 1mg, 5mg, and 25mg
|
Drug: Placebo
Placebo will be provided as white, opaque gelatin capsules in sham strengths of 1mg, 5mg, and 25mg
|
|
Active Comparator: 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.
|
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.
|
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.
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Criteria
Inclusion Criteria:
- Diagnosis of ADHD per DSM-IV TR criteria
- Score > 2 on at least 6 of 9 items in at least 1 subscale of the CAARS-INV
- Score > 4 (at least moderate) on the Clinical Global Impression-Severity (CGI-S) index
- Age 18 - 65, male or female
- 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
- Able to understand and sign informed consent
Exclusion Criteria:
- Current DSM-IV Axis I psychiatric disorder other than ADHD; use of MINI to exclude other major DSM-IV TR psychiatric diagnoses
- Known or suspected drug abuse within the last 12 months prior to Screening
- Urine drug screen positive for illegal or non-prescribed drugs at Screening
- Patients at imminent risk of suicide or of danger to themselves or others
- 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.
- Any other restricted or prohibited drugs.
- Other concomitant medications that have been changed within 4 weeks prior to Screening
- Unable to comply with study procedures in opinion of investigator, including CogState ADHD test battery
- History of significant other major or unstable neurological, metabolic, hepatic, renal, hematological, pulmonary, CV, GI, or urological disorder; or diagnosis of major depressive disorder
- Myocardial infarction within past year
- Seizure disorder within past year
- Type 1 diabetes mellitus (DM); type 2 DM that requires medication (diet-controlled allowed)
- HbA1C > 7.4 at Screening
- BMI < 15 or > 35; male weight < 100 lbs; female weight < 80 lbs.
- Current TB or known systemic infection (HBV, HCV, HIV)
- Clinically significant finding on physical exam
- 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
- Women of child-bearing potential and men unwilling or unable to use accepted methods of birth control
- Women with a positive pregnancy test, or who are lactating
- Participation in another clinical trial in last 3 months prior to Screening
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01124708
Locations
| United States, Florida | |
| Florida Clinical Research Center, LLC | |
| Bradenton, Florida, United States, 34208 | |
| Clinical Neuroscience Solutions, Inc. | |
| Jacksonville, Florida, United States, 32216 | |
| Fidelity Clinical Research, Inc | |
| Lauderhill, Florida, United States, 33319 | |
| Florida Clinical Research Center, LLC | |
| Maitland, Florida, United States, 32751 | |
| Scientifc Clinical Research, Inc. | |
| North Miami, Florida, United States, 33161 | |
| Clinical Neuroscience Solutions, Inc. | |
| Orlando, Florida, United States, 32806 | |
| United States, Georgia | |
| Atlanta Center For Clinical Research | |
| Atlanta, Georgia, United States, 30308 | |
| United States, New Jersey | |
| CRI Worldwide, LLC (Lourdes Division) | |
| Willingboro, New Jersey, United States, 08046 | |
| United States, Ohio | |
| Neuro-Behavioral Clinical Research, Inc. | |
| Canton, Ohio, United States, 44718 | |
| Midwest Clinical Research Center | |
| Dayton, Ohio, United States, 45417 | |
| United States, Oregon | |
| Oregon Center For Clinical Investigations, Inc. (OBBI, Inc.) | |
| Portland, Oregon, United States, 97210 | |
| United States, Pennsylvania | |
| CRI Worldwide, LLC (Kirkbride Division) | |
| Philadelphia, Pennsylvania, United States, 19139 | |
| United States, Tennessee | |
| Clinical Neuroscience Solutions, Inc. | |
| Memphis, Tennessee, United States, 38119 | |
| United States, Texas | |
| FutureSearch Clinical Trials, LP | |
| Austin, Texas, United States, 78756 | |
| Claghorn-Lessem Research Clinic | |
| Houston, Texas, United States, 77008 | |
| United States, Vermont | |
| Fletch Allen Health Care, Dept. of Psychiatry, Univ. of Vermont | |
| Burlington, Vermont, United States, 05401 | |
Sponsors and Collaborators
Targacept Inc.
Investigators
| Principal Investigator: | Paul Newhouse, MD | Fletcher Allen Health Care, Dept. of Psychiatry |
More Information
No publications provided
| Responsible Party: | Targacept Inc. |
| ClinicalTrials.gov Identifier: | NCT01124708 History of Changes |
| Other Study ID Numbers: | TC-5619 Adult ADHD, PRO-05619-CRD-002 |
| Study First Received: | May 5, 2010 |
| Last Updated: | October 28, 2011 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Targacept Inc.:
|
ADHD Attention Deficit Hyperactive Disorder |
Additional relevant MeSH terms:
|
Attention Deficit Disorder with Hyperactivity Hyperkinesis Attention Deficit and Disruptive Behavior Disorders Mental Disorders Diagnosed in Childhood Mental Disorders |
Dyskinesias Neurologic Manifestations Nervous System Diseases Signs and Symptoms |
ClinicalTrials.gov processed this record on June 18, 2013