Open-label, Long-term Safety Extension Study of AFQ056 in Parkinson's Patients With L-dopa Induced Dyskinesias

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01491932

Collaborator

(none)

129

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is to evaluate long-term safety, tolerability and efficacy for AFQ056 in patients who have completed an AFQ056A study in Parkinson's disease L-dopa induced dyskinesias (PD-LID).

Condition or Disease	Intervention/Treatment	Phase
Dyskinesias Parkinson Disease Movement Disorders Parkinsonian Disorders Anti-Dyskinesia Agents	Drug: AFQ056	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

129 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-label Treatment Study to Evaluate the Safety, Tolerability and Efficacy of AFQ056 in Parkinson's Patients With L-dopa Induced Dyskinesias

Study Start Date :

Mar 1, 2012

Actual Primary Completion Date :

Oct 1, 2013

Actual Study Completion Date :

Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AFQ056 Patients entering the study will be titrated to target dose of AFQ056 twice daily or the highest tolerated dose at weekly intervals.	Drug: AFQ056 AFQ056 will be supplied as oral capsules.

Arm

Intervention/Treatment

Experimental: AFQ056

Patients entering the study will be titrated to target dose of AFQ056 twice daily or the highest tolerated dose at weekly intervals.

Drug: AFQ056

AFQ056 will be supplied as oral capsules.

Outcome Measures

Primary Outcome Measures

Incidence rate of adverse events including serious adverse events [Monitored for the duration of the study (anticipated to be an average of 3 years)]
The occurrence of adverse events would be sought by non-directive questioning of the patient at each visit. Adverse events may also be detected when they are volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessment.
Severity of adverse events including serious adverse events [Monitored for the duration of the study (anticipated to be an average of 3 years)]
The occurrence and severity of adverse events would be sought by non-directive questioning of the patient at each visit. Adverse events may also be detected when they are volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessment.
Change in vital signs from baseline to Weeks 1, 2, 4, 8, 12, Months 6, 9, 12, every 6 months thereafter. [Assessed at Day -14 to -3, Day 1, Weeks 1, 2, 4, 8, 12, Months 6, 9, 12, every 6 months thereafter]
Pulse and blood pressure at each visit as indicated above. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Changes in hematology/blood chemistry and urinalysis laboratory evaluations from baseline to Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter [Assessed at Day -14 to -3, Day 1(only urinalysis and only done if abnormalities), Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter]
Standard hematology with differential, aPTT, PT/INR;, clinical chemistry consists of albumin, alkaline phosphatase, amylase, total bilirubin, calcium, cholesterol, creatinine, CK, γ-GT, glucose, lipase, lactate dehydrogenase, inorganic phosphorus, magnesium, potassium, total protein, AST, ALT, sodium, triglycerides, urea and uric acid, FSH, LH, oxytocin, prolactin, TBG, TSH, and T4; urinalysis (specific gravity, protein, glucose and blood) If a patient discontinues in between these visits, these will be assessed at the time of discontinuation.
Change in ECGs from baseline to Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter [Assessed at Day -14 to -3, Day 1, (repeated if abnormalities seen), Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter]
A standard 12-lead ECG will be performed. A central facility will be used for interpretation and analysis of the ECGs. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Change in Unified Parkinson's Disease Rating Scale (UPDRS) part III scores from baseline to Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter [Assessed at Day 1, Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter]
Part III of the UPDRS (items 18-31; total score 0-56), has been proven to be a reliable instrument in assessing the anti-parkinsonian effect in PD patients. This scale measures 14 items such as speech, facial expression, tremor, action or postural tremor, rigidity, finger taps, hand movement, alternating movement, leg agility, arising from a chair, posture, gait, postural stability, and bradykinesia. A higher score is indicative of worsening of symptoms. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Incidence of AEs related to an exacerbation of the underlying movement disorder Parkinson's disease [Monitored for the duration of the study (anticipated to be an average of 3 years)]
The occurrence of adverse events relating to the underlying movement disorder Parkinson's disease would be sought by non-directive questioning of the patient at each visit. Adverse events may also be detected when they are volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessment.

Secondary Outcome Measures

Change in mAIMS (modified Abnormal Involuntary Movement Scale) total score from baseline to Weeks 1, 2, 4, 8, 12, Months 6, 9, 12, every 6 months thereafter. [Assessed at Day 1, Weeks 1, 2, 4, 8, 12, Months 6, 9, 12, every 6 months thereafter]
The AIMS is a scale for assessing dyskinesia. The modified version of this scale used in this study focuses on 6 different parts of the body and rates abnormal movements from 0 (absence of dyskinesia) to 4 (severe) (maximal score, 24). If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Change in Revised Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS) scores (patient and caregiver versions) from baseline to Weeks 4, 12, Months 6, 9, 12, every 6 months thereafter [Assessed at Day 1, Weeks 4, 12, Months 6, 9, 12, every 6 months thereafter]
The LFADLDS is a questionnaire asking the patient about the degree to which dyskinesia interferes with activities of daily living. The LFADLDS is modified from the ADL section of the UPRDS (part II). Specific definitions for severity rating codes (range, 0-4 for each task) will be provided for reproducibility of results. A higher score indicates more severe impairment. Two versions of the revised LFADLDS will be used in this study: a patient version and a caregiver version. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Change in score for items 32, 33, and 34 of Part IV of the UPDRS from baseline to Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter [Assessed at Day 1, Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter]
The UPDRS is a standardized instrument for measuring the disease state of PD patients. Question 32 assesses duration of dyskinesias expressed in percentage of the day . Question 33 makes a historical assessment of disability due to dyskinesia during the previous week (not disabling, mildly disabling, moderately disabling, severely disabling, completely disabling). Question 34 of part IV assesses how painful the dyskinesias are from 0 (no painful dyskinesias) to 4 (marked). If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Change in Mini Mental State Exam (MMSE) score from baseline to Months 6, 12, every 6 months thereafter [Assessed at Day -14 to -3, Day 1 (only if not done in the respective core study), Months 6, 12, every 6 months thereafter]
The MMSE is a brief test of cognitive dysfunction consisting of five sections (orientation, registration, attention-calculation, recall, and language) administered by a health care professional. The MMSE results in total possible score of 30, with higher scores indicating better function. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Change in the Scales for outcomes in Parkinson's disease - Psychiatric Complications (SCOPA-PC) score from baseline to Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter [Assessed at Day 1, Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter]
The SCOPA-PC is an easily administered semi-structured, questionnaire developed for the assessment of psychiatric symptoms, including compulsive behavior, in Parkinson's disease patients administered by a clinician with input provided by patient and caregiver. The total SCOPA score ranges from 0-21, with higher scores reflecting more psychiatric complications. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Proportion of patients who have suicidal ideation and behavior as mapped to Columbia Classification Algorithm for Suicide assessment (C-CASA) using data from Columbia-Suicide Severity Rating Scale (C-SSRS) [Monitored for the duration of the study (anticipated to be an average of 3 years)]
The C-SSRS assesses suicidal ideation/behavior using a patient interview. The data is mapped to Columbia Classification Algorithm for Suicide assessment. The code and categories are: completed suicide, suicide attempt, preparatory actions toward imminent suicide behavior, suicidal ideation, self-injurious behavior without suicidal intent. The proportion of patients who are coded in the categories above, the proportion of patients with any suicidal behavior engaged in during the study, and the proportion of patients with suicidality will be summarized.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients who have completed a previous AFQ056A study or are eligible as defined in the core study protocol
Outpatients
Patients who have a primary caregiver willing and able to assess the condition of the patient throughout the study in accordance with protocol requirements

Exclusion Criteria:

Atypical or secondary form of Parkinson's disease
History of surgical treatment for PD including deep brain stimulation
Advanced, severe, or unstable disease (other than PD)
History of malignancy
Evidence of dementia
Untreated/ineffectively treated mental disorders
Treatment with certain prohibited medications
Abnormal lab values or heart abnormalities
Pregnant or nursing women

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Englewood	Colorado	United States	80113
2	Novartis Investigative Site	Kansas City	Kansas	United States	66160
3	Novartis Investigative Site	Milwaukee	Wisconsin	United States	53233
4	Novartis Investigative Site	Innsbruck		Austria	A-6020
5	Novartis Investigative Site	Linz		Austria	A-4020
6	Novartis Investigative Site	Vienna		Austria	A-1220
7	Novartis Investigative Site	London	Ontario	Canada	N6A 4G5
8	Novartis Investigative Site	Clermont-Ferrand Cedex 1		France	63003
9	Novartis Investigative Site	Lille Cedex		France	59037
10	Novartis Investigative Site	Pessac		France	33604
11	Novartis Investigative Site	Beelitz-Heilstaetten		Germany	14547
12	Novartis Investigative Site	Berlin		Germany	12163
13	Novartis Investigative Site	Bochum		Germany	44791
14	Novartis Investigative Site	Kassel		Germany	34128
15	Novartis Investigative Site	Leipzig		Germany	04103
16	Novartis Investigative Site	München		Germany	81675
17	Novartis Investigative Site	Stadtroda		Germany	07646
18	Novartis Investigative Site	Westerstede/Oldenburg		Germany	26655
19	Novartis Investigative Site	Kaposvár		Hungary	7400
20	Novartis Investigative Site	Szeged		Hungary	H-6725
21	Novartis Investigative Site	Brescia	BS	Italy	25123
22	Novartis Investigative Site	Pisa	PI	Italy	56126
23	Novartis Investigative Site	Roma	RM	Italy	00163
24	Novartis Investigative Site	Roma	RM	Italy	00179
25	Novartis Investigative Site	Bratislava		Slovakia	82606
26	Novartis Investigative Site	Bratislava		Slovakia	83305
27	Novartis Investigative Site	Barcelona	Catalunya	Spain	08036
28	Novartis Investigative Site	Sant Cugat	Catalunya	Spain	08190
29	Novartis Investigative Site	San Sebastian	Pais Vasco	Spain	20014
30	Novartis Investigative Site	Barcelona		Spain	08025
31	Novartis Investigative Site	Madrid		Spain	28006
32	Novartis Investigative Site	Bern		Switzerland	3010