Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette's Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of an investigational compound designated PF-03654746 compared to placebo in the treatment of adults with Tourette's Syndrome. The study will also explore the pharmacokinetics of PF-03654746 in adults with Tourette's Syndrome.

Detailed Description
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The study was terminated 11-Apr-2012 due to an internal reassessment of priorities by the sponsor. The decision to terminate was not based on any safety or efficacy concerns.

Official Title
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A Phase 2 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Cross-Over Study Of The Safety And Efficacy Of PF-03654746 In Adults With Tourette's Syndrome

Conditions
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Tourette's Syndrome

Intervention / Treatment
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* Drug: PF-03654746
* Drug: Placebo
* Drug: Placebo
* Drug: PF-03654746


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary diagnosis of Tourette's Syndrome in English-speaking male or female adults 18 to 55 years of age who are in generally good health. Free of medications to treat tics for at least 6 weeks prior to randomization. Females of childbearing potential must use medically acceptable birth control for the duration of the study and for 28 days after study participation. Exclusion Criteria: Tic treatment including protocol-specified drugs, training in tic-suppressing behavioral techniques, habit reversal training or use of Onabotulinum toxin A injection. History or neurologic evidence of a secondary tic disorder, psychosis, bipolar disorder, tardive dyskinesia, untreated or unstable DSM-IV Axis I disorder requiring treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PF-03654746<br>Subjects are randomized to either active drug or placebo in Period 1; in Period 2 the sequence is reversed. | Drug: PF-03654746<br>* 20-day dose titration phase: all dosages in capsules starting at 0.25 mg qd x 5 d, then 0.5 mg qd x 5 d, then 1.0 mg qd x 5 d, then 2.0 mg qd x 5 d. If a subject has intolerable, severe, or serious AEs after taking 2 mg qd for 1 to 5 days of dosing, the dose will be decreased by the investigator to 1 mg qd. If, in the investigator's opinion, the subject is determined to be unlikely to tolerate continued dosing at a dose of 1 mg qd, the subject should be discontinued from the study. Subjects remaining in the study will proceed to the 3-week Stable Dosing Phase; doses will be 2 mg daily x 21 days or 1 mg daily x 21 days.<br>Drug: Placebo<br>* once daily dosing of placebo capsules following the dosing scheme described in 1.1.<br>|
| Placebo Comparator: Placebo<br>Subjects are randomized to either active drug or placebo in Period 1; in Period 2 the sequence is reversed. | Drug: Placebo<br>* once daily dosing of placebo capsules following the dosing scheme described in 1.1<br>Drug: PF-03654746<br>* 20-day dose titration phase: all dosages in capsules starting at 0.25 mg qd x 5 d, then 0.5 mg qd x 5 d, then 1.0 mg qd x 5 d, then 2.0 mg qd x 5 d. If a subject has intolerable, severe, or serious AEs after taking 2 mg qd for 1 to 5 days of dosing, the dose will be decreased by the investigator to 1 mg qd. If, in the investigator's opinion, the subject is determined to be unlikely to tolerate continued dosing at a dose of 1 mg qd, the subject should be discontinued from the study. Subjects remaining in the study will proceed to the 3-week Stable Dosing Phase; doses will be 2 mg daily x 21 days or 1 mg daily x 21 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Tic Score (Yale Global Tic Severity Scale) from baseline (D0) to end of the 3 wk stable dosing phase (D41)(primary). Average of the 2 assessments of Total Tic Score in 3 wk stable dosing phase is secondary. Score 0-50 (50 = severe) |  | Period 1: Days 0, 10, 20, 34, 41; Period 2: Days 0, 10, 20, 34, 41 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Tic Symptom Self Report from baseline to end of 3-wk stable dosing phase (primary); average of 2 assessments of TSSR during 3-wk stable dosing phase is 2ndary. Each symptom is scored 0-3; higher score is worse. |  | Period 1: Days 0, 10, 20, 34, 41; Period 2: Days 0, 10, 20, 34, 41 | 
| Change in Premonitory Urge for Tic Scale from baseline to end of 3-wk stable dosing phase (primary); average of 2 assessments of PUTS during 3-wk stable dosing phase is 2ndary. Score 9-36; higher score is worse. |  | Period 1: Days 0, 10, 20, 34, 41; Period 2: Days 0, 10, 20, 34, 41 | 
| Change in Clinical Global Impression of Severity from baseline to end of 3-wk stable dosing phase. Score 1-7; higher scores indicate more severity. |  | Period 1, Days 0, 41; Period 2: Days 0, 41 | 
| Change in Clinical Global Impression of Improvement from baseline to end of 3-wk stable dosing phase (primary); average of 2 assessments during 3-wk stable dosing phase is 2ndary. Score 1-7; higher score is worse. |  | Period 1: Days 10, 20, 34, 41; Period 2: Days 10, 20, 34, 41 | 
| Change in Conners' Continuous Performance Test II from baseline to end of 3-wk stable dosing phase. Calculated T-scores (under 40 to 65 and over); higher score is worse. |  | Period 1: Days 0, 20, 41; Period 2: Days 0, 20, 41 | 
| Change in Medical Outcomes Study--Sleep Scale from baseline to end of 3-wk stable dosing phase. Score 0-100; a higher score reflect greater amount of quality implied by subscale name. |  | Period 1: Days 0, 10, 20, 34, 41; Period 2: Days 0, 10, 20, 34, 41 | 
| Change in Columbia Suicide Severity Rating Scale from baseline to end of 3-wk stable dosing phase. |  | Screening; Period 1: Days 0, 10, 20, 34, 41; Period 2: Days 0, 10, 20, 34, 41 | 
| Suicide Behaviors Questionnaire-Revised. Total score greater than 8 require assessment by clinician or mental health professional skilled in evaluation of suicidality. |  | Up to 21 days prior to Baseline (Day 0) | 
| Change in Yale-Brown Obsessive-Compulsive Scale from baseline to end of 3-wk stable dosing phase. Items 1-10 have score range of 0-40; higher score is worse. |  | Period 1: Days 0, 41; Period 2: Days 0, 41 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tourette's Syndrome in adults, Safety and Efficacy, Randomized, Placebo Control, Cross-over