Back to resultsEfficacy, Safety, and Tolerability of TC-5619 in Adults With Attention Deficit/Hyperactivity Disorder (ADHD)
Primary Purpose
ADHD
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
TC-5619-238
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for ADHD focused on measuring ADHD, Attention Deficit Hyperactive Disorder
Eligibility 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
Sites / Locations
- Florida Clinical Research Center, LLC
- Clinical Neuroscience Solutions, Inc.
- Fidelity Clinical Research, Inc
- Florida Clinical Research Center, LLC
- Scientifc Clinical Research, Inc.
- Clinical Neuroscience Solutions, Inc.
- Atlanta Center For Clinical Research
- CRI Worldwide, LLC (Lourdes Division)
- Neuro-Behavioral Clinical Research, Inc.
- Midwest Clinical Research Center
- Oregon Center For Clinical Investigations, Inc. (OBBI, Inc.)
- CRI Worldwide, LLC (Kirkbride Division)
- Clinical Neuroscience Solutions, Inc.
- FutureSearch Clinical Trials, LP
- Claghorn-Lessem Research Clinic
- Fletch Allen Health Care, Dept. of Psychiatry, Univ. of Vermont
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
Placebo
TC-5619
Arm Description
Placebo will be provided as white, opaque gelatin capsules in sham strengths of 1mg, 5mg, and 25mg
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.
Outcomes
Primary Outcome Measures
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)]
Secondary Outcome Measures
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)]
CogState ADHD Battery
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
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
CAARS-S total score [Time frame: Week -3, Day 1, Week 1, Week 4, Week 8, Week 12,Early Withdrawal (EW)]
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01124708
Brief Title
Efficacy, Safety, and Tolerability of TC-5619 in Adults With Attention Deficit/Hyperactivity Disorder (ADHD)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2011
Overall Recruitment Status
Completed
Study Start Date
May 2010 (undefined)
Primary Completion Date
February 2011 (Actual)
Study Completion Date
February 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Targacept Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ADHD
Keywords
ADHD, Attention Deficit Hyperactive Disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
134 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo will be provided as white, opaque gelatin capsules in sham strengths of 1mg, 5mg, and 25mg
Arm Title
TC-5619
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
TC-5619-238
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
Placebo will be provided as white, opaque gelatin capsules in sham strengths of 1mg, 5mg, and 25mg
Primary Outcome Measure Information:
Title
CAARS-INV ADHD-rating scale
Description
•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)]
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
CAARS-INV subscales
Description
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)]
Time Frame
Week 12
Title
CogState ADHD Battery
Description
CogState ADHD test battery [Time frame: Week -3, Day 1, Week 1, Week 4, Week 8, Week 12,Early Withdrawal (EW)]
Time Frame
Week 12
Title
CogState Stop-Signal Task scores
Description
CogState Stop-Signal Task scores [Time frame: Week -3, Day 1, Week 1, Week 4, Week 8, Week 12,Early Withdrawal (EW)]
Time Frame
Week 12
Title
CAARS-Self Rating (CAARS-S) total score
Description
CAARS-S total score [Time frame: Week -3, Day 1, Week 1, Week 4, Week 8, Week 12,Early Withdrawal (EW)]
Time Frame
Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Newhouse, MD
Organizational Affiliation
Fletcher Allen Health Care, Dept. of Psychiatry
Official's Role
Principal Investigator
Facility Information:
Facility Name
Florida Clinical Research Center, LLC
City
Bradenton
State/Province
Florida
ZIP/Postal Code
34208
Country
United States
Facility Name
Clinical Neuroscience Solutions, Inc.
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32216
Country
United States
Facility Name
Fidelity Clinical Research, Inc
City
Lauderhill
State/Province
Florida
ZIP/Postal Code
33319
Country
United States
Facility Name
Florida Clinical Research Center, LLC
City
Maitland
State/Province
Florida
ZIP/Postal Code
32751
Country
United States
Facility Name
Scientifc Clinical Research, Inc.
City
North Miami
State/Province
Florida
ZIP/Postal Code
33161
Country
United States
Facility Name
Clinical Neuroscience Solutions, Inc.
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Atlanta Center For Clinical Research
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
CRI Worldwide, LLC (Lourdes Division)
City
Willingboro
State/Province
New Jersey
ZIP/Postal Code
08046
Country
United States
Facility Name
Neuro-Behavioral Clinical Research, Inc.
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
Midwest Clinical Research Center
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45417
Country
United States
Facility Name
Oregon Center For Clinical Investigations, Inc. (OBBI, Inc.)
City
Portland
State/Province
Oregon
ZIP/Postal Code
97210
Country
United States
Facility Name
CRI Worldwide, LLC (Kirkbride Division)
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19139
Country
United States
Facility Name
Clinical Neuroscience Solutions, Inc.
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38119
Country
United States
Facility Name
FutureSearch Clinical Trials, LP
City
Austin
State/Province
Texas
ZIP/Postal Code
78756
Country
United States
Facility Name
Claghorn-Lessem Research Clinic
City
Houston
State/Province
Texas
ZIP/Postal Code
77008
Country
United States
Facility Name
Fletch Allen Health Care, Dept. of Psychiatry, Univ. of Vermont
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
12. IPD Sharing Statement
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Efficacy, Safety, and Tolerability of TC-5619 in Adults With Attention Deficit/Hyperactivity Disorder (ADHD)
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