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

Sponsor

Pfizer (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT01475383

Collaborator

(none)

Enrollment

Location

Arms

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Tourette's Syndrome	Drug: PF-03654746 Drug: Placebo Drug: Placebo Drug: PF-03654746	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2012

Actual Primary Completion Date :

Apr 1, 2012

Actual Study Completion Date :

Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: PF-03654746 Subjects are randomized to either active drug or placebo in Period 1; in Period 2 the sequence is reversed.	Drug: PF-03654746 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. Drug: Placebo once daily dosing of placebo capsules following the dosing scheme described in 1.1.
Placebo Comparator: Placebo Subjects are randomized to either active drug or placebo in Period 1; in Period 2 the sequence is reversed.	Drug: Placebo once daily dosing of placebo capsules following the dosing scheme described in 1.1 Drug: PF-03654746 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.

Arm

Intervention/Treatment

Active Comparator: PF-03654746

Subjects are randomized to either active drug or placebo in Period 1; in Period 2 the sequence is reversed.

Drug: PF-03654746

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.

Drug: Placebo

once daily dosing of placebo capsules following the dosing scheme described in 1.1.

Placebo Comparator: Placebo

Subjects are randomized to either active drug or placebo in Period 1; in Period 2 the sequence is reversed.

Drug: Placebo

once daily dosing of placebo capsules following the dosing scheme described in 1.1

Drug: PF-03654746

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.