Study Evaluating The Safety, Tolerability And Brain Function Of 2 Doses Of PF-0254920 In Subjects With Early Huntington's Disease

NCT01806896 | Completed Phase 2 Results DMC

• 2 other identifiers: A82410162012-004432-31
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the Safety, Tolerability and Brain Function of 2 doses of PF-0254920 in Subjects with Early Huntington's Disease.

Conditions

Huntington's Disease

Outcome Measures

Primary Outcomes (10)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)

  An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of treatment and up to the follow-up period that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-serious AEs.

  Baseline up to Day 38

• Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern (Without Regard to Baseline Abnormality)

  The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell \[RBC\] count, platelet count, white blood cell \[WBC\] count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen \[BUN\], creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], total and direct bilirubin, alkaline phosphatase, uric acid, albumin, and total protein; urinalysis (pH, glucose, protein/albumin, hemoglobin/blood, ketones/acetone, nitrites, leukocyte esterase, microscopy \[if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase\]); others (urine/serum pregnancy test, glycosylated hemoglobin \[HbA1c, if diabetic\]).

  Baseline up to Day 38

• Number of Participants With Potentially Clinically Significant Vital Signs Findings

  Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine/sitting pulse rate less than (\<)40 or greater than (\>)120 beats per minute (bpm), standing pulse rate \<40 or \>140 bpm; systolic blood pressure (SBP) of greater than or equal to (\>=)30 millimeters of mercury (mmHg) change from baseline or SBP \<90 mmHg, diastolic blood pressure (DBP) \>=20 mmHg change from baseline or DBP \<50 mmHg.

  Baseline up to Day 38

• Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings

  ECG parameters included PR interval, QRS complex, and corrected QT interval using Fridericia's formula (QTcF). Criteria for ECG changes meeting potential clinical concern included: PR interval ≥200 milliseconds (msec) or ≥25% increase when baseline is \>100 msec; QRS interval ≥50% increase from baseline when baseline is less than or equal to (\<=)200 msec; and QTcF ≥450 msec or ≥30 msec increase from baseline.

  Baseline up to Day 38

• Number of Participants With Change From Baseline in Body Weight of >=7%

  Weight assessment was performed by a study physician or a trained study nurse and was included in the physical examination.

  Baseline up to Day 38

• Categorical Summary of Participants Meeting Stopping Criteria

  Absolute neutrophil count (ANC) and WBC were monitored for safety. Participants with WBC \<3000 but \>=2000 cells/mm\^3 or ANC \<1500 but \>=1000 cells/mm\^3 were to have study treatment suspended. Participants with WBC \<2000 or ANC \<1000 cells/mm\^3 were to be discontinued from study participation.

  Baseline up to Day 38

• Change From Baseline in Unified Huntington Disease Rating Scale (UHDRS) Total Motor Score at Day 28

  The UHDRS is a clinical rating scale to provide a uniform assessment of the clinical features and course of Huntington Disease. The Total Motor Score (TMS) is 1 of the 6 components of UHDRS, includes 31 items, and ranges from a scale of 0 to 124 (higher scores indicate more severe disease).

  Baseline, Day 28

• Number of Participants With Suicidal Tendencies (C-SSRS Mapped to C-CASA) at Baseline

  C-SSRS is a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Yes/No responses are mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories: completed suicide, suicide attempt, preparatory acts towards imminent suicidal behavior, suicidal ideation, and self-injurious behavior, or no suicidal intent. A participant could have a yes or no response in more than 1 category.

  Baseline (Day 1)

• Number of Participants With Suicidal Tendencies (C-SSRS Mapped to C-CASA) at Day 7

  C-SSRS is a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Yes/No responses are mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories: completed suicide, suicide attempt, preparatory acts toward imminent suicidal behavior, suicidal ideation, and self-injurious behavior, or no suicidal intent. A participant could have a yes or no response in more than 1 category.

  Day 7

• Number of Participants With Suicidal Tendencies (C-SSRS Mapped to C-CASA) at Day 28

  C-SSRS is a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Yes/No responses are mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories: completed suicide, suicide attempt, preparatory acts toward imminent suicidal behavior, suicidal ideation, and self-injurious behavior, or no suicidal intent. A participant could have a yes or no response in more than 1 category.

  Day 28

Secondary Outcomes (2)

• Change From Baseline in Functional Magnetic Resonance Imaging (fMRI) in Monetary Incentive Delay (MID) Task at Day 28

  Baseline (Day 1), Day 28

• Change From Baseline in Grip Strength Incentive Motivation Task at Day 28: Percent of Maximum Voluntary Contraction (MVC)

  Baseline, Day 28

Study Arms (4)

20 mg Arm Cohort A

EXPERIMENTAL

Drug: PF-02545920

Placebo Arm Cohort A

PLACEBO COMPARATOR

Drug: Placebo

5 mg Arm Cohort B

EXPERIMENTAL

Drug: PF-02545920

Placebo Arm Cohort B

PLACEBO COMPARATOR

Drug: Placebo

Interventions

PF-02545920 DRUG

* Dose will be titrated up every 2 days by 5mg increments: 5mg Days 1-2, 10mg days 3-4, 15mg days 5-6, and reach 20 mg from Days 7 to Day28. * Orally, approx. Q12H (range 10-14 hours), administered at least one hour prior to, or two hours after meals. * Treatment for 28 days.

20 mg Arm Cohort A

Placebo DRUG

\- Orally, approx. Q12H (range 10-14 hours), administered at least one hour prior to, or two hours after meals. Dosing for 28 days.

Placebo Arm Cohort A

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have a diagnosis of Huntington's Disease
• a CAG repeat expansion equal or great than 39
• a Unified Huntington Disease Rating Scale (UHDRS) Total Motor Score equal or greater than 5 and less than 60
• a UHDRS Total Functional Capacity equal or greater than 9

You may not qualify if:

• Subjects with evidence or history of severe acute or chronic medical condition or laboratory abnormality, or significant neurological disorder other than HD.
• Treatment with any antipsychotic medication within 5 weeks of enrollment

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Centre d'Investigation Clinique (CIC)/ Institut du Cerveau et de la Möelle Epinière (ICM)

Paris, 75651, France

Location

MeSH Terms

Conditions

Huntington Disease

Interventions

2-((4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxy)methyl)quinoline

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Limitations and Caveats

The study was initially designed to include 20 mg BID and 5 mg BID. Interim analysis of 20 mg BID/placebo supported the development of PF-02545920, and therefore, 5 mg BID was not enrolled.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2013
• First Posted: March 7, 2013
• Study Start: September 1, 2013
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: December 14, 2017
• Results First Posted: December 14, 2017

Record last verified: 2017-05

Locations

FR (1)