A study to evaluate the safety and tolerability of tozadenant in Parkinson disease patients who are taking levodopa and experiencing "wearing off"

• Register: EUCTR
• Last refreshed on: 4 December 2018
• Main ID: EUCTR2016-003961-25-DE
• Date of registration: 01/02/2017
• Prospective Registration: Yes
• Primary sponsor: Biotie Therapies
• Public title: A study to evaluate the safety and tolerability of tozadenant in Parkinson disease patients who are taking levodopa and experiencing "wearing off"
• Scientific title: A Multicenter, Open-Label Study to Evaluate the Safety and Tolerability of Tozadenant as Adjunctive Therapy in Levodopa-Treated Patients with Parkinson’s Disease Experiencing End of Dose “Wearing-Off”
• Date of first enrolment: 30/06/2017
• Target sample size: 450
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003961-25
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, Czech Republic, European Union, Germany, Hungary, Italy, Spain, United Kingdom, United States

Contacts

• Name: Clinical Operations
• Affiliation: AMS Advanced Medical Services

• Name: Clinical Operations
• Affiliation: AMS Advanced Medical Services

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provide written informed consent.
2. Patient is considered reliable and capable of adhering to the protocol according to the judgment of the investigator.
3. Patient has a documented history of idiopathic Parkinson’s disease consistent with the UK Parkinson’s Disease Society Brain Bank Diagnostic criteria prior to the Screening Visit.
4. Patient has a PD duration of at least 3 years from diagnosis.
5. Patient has a modified Hoehn and Yahr stage 2–4 when in OFF state (estimated) and = 3 in ON state.
6. Patient is male or female and 30–80 years old (inclusive) at Screening.
7. Patient must have a good response to levodopa in the opinion of the investigator, be taking at least four doses of a levodopa-containing medication per day, and at least one other concomitant anti PD medication (dopamine agonists, MAO-B inhibitors, anticholinergic agents, amantadine or entacapone).
8. Patient is maintained on a regimen of permitted anti-PD medications that has been stable for at least 4 weeks prior to Screening.
9. Patients must have been taking a levodopa-containing anti-PD medication continuously for at least the previous 12 months and must be currently experiencing end-of-dose “wearing-off” with at least 2.5 hours of OFF time per day as confirmed by a 3-day Baseline diary.
10. Patient must have achieved the following results for PD diary training, practice diary collection, and Baseline diary recordings:
a. During a diary concordance session with an approved PD diary trainer/rater (minimum 2.5 hours), patient achieved at least 80% overall diary concordance including at least 1 OFF interval.
b. Returned a valid 3 day (i.e., 3 consecutive 24 hour periods) practice diary.
c. Returned valid diary recordings for each of the 3 consecutive days preceding the Baseline Visit that indicated at least 2.5 hours of OFF time on each of the 3 days.
11. Contraception:
a. Women of childbearing potential must use an acceptable method of contraception starting 4 weeks prior to study drug administration and for a minimum of 1 month after study completion. Otherwise, women must be postmenopausal (at least 1year absence of vaginal bleeding or spotting, and confirmed by follicle stimulating hormone [FSH] = 40 mIU/mL [or = 40 IU/L] if less than 2 years postmenopausal) or be surgically sterile.
b. Men with a potentially fertile partner must have had a vasectomy or be willing to use an acceptable method of contraception for the duration of the study and for 3 months after study drug discontinuation.
For men and women: Acceptable methods of contraception include use of a condom with spermicide; oral, implantable or injectable contraceptives; intrauterine device (IUD); diaphragm with spermicide; or, diaphragm with condom.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 158
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 292

Exclusion criteria:
1. Patient previously participated in any study with tozadenant.
2. Patient is currently participating in or has participated in another study and received an IMP within 5 half-lives of the IMP.
3. Patient has any form of secondary or atypical parkinsonism (e.g., drug-induced, post stroke).
4. Body mass index (BMI) greater than 40.
5. QTcF interval of =?500 msec at Screening (Visit 1) or the patient has an average QTcF interval =?450 msec for males or =?470 msec for females at Baseline (Visit 2).
6. Known diagnosis of malignant melanoma.
7. History of neurosurgical intervention for PD, (the placement of deep brain stimulator electrodes 12 months prior to screening is allowed); subjects with DBS must not be experiencing any clinically meaningful side effects related to the procedure, the device, or stimulation.
8. Grade 2 hypertension (supine systolic BP =?160 or diastolic BP =?100 mmHg), treated or untreated
9. Patient with a history of hypertensive crisis unless the underlying cause has been removed (e.g. stenting for renal artery stenosis).
10. Patient has a history of chronic alcohol or drug abuse within the last 2 years.
11. Patient is taking apomorphine, budipine, istradefylline, tolcapone, or DUOPA™/Duodopa®, within 4 weeks prior to Screening or is likely to require any of these drugs during the study.
12. Current treatment with antipsychotics; however, quetiapine administered at doses of =?100 mg per day and pimavanserin are permitted if the patient has been on a stable daily dose for at least 4 weeks before Screening. PRN (as needed) dosing is not permitted.
13. Patient has taken digoxin within 4 weeks prior to Screening or is likely to require digoxin during the study.
14. Hyperthyroidism or hypothyroidism, unless all of the following conditions are met:
a. Patient has received a stable dose of thyroid medication for at least 3 months before the Baseline Visit.
b. TSH concentrations are in the normal range (±?10% as a window either side of the normal range).
c. Patient is clinically euthyroid.
15. Any out-of-range laboratory values at Screening that have not been reviewed and documented as not clinically significant by the investigator.
16. A score of 17. Patients with a current episode of major depression. Patients receiving treatment for depression with antidepressants may be enrolled if they have been on a stable daily dose of the antidepressant for at least 8 weeks before the Baseline Visit.
18. Patient has a recent history of suicide attempt (defined as an active, interrupted or aborted attempt within the past 5 years), or reports suicidal ideation in the past 6 months as indicated by a positive response (‘Yes’) to either Question 4 or Question 5 of the C-SSRS performed at the Screening or Baseline Visit.
19. Patient has evidence of an impulse control disorder (ICD) (i.e., one or more positive modules) according to the Modified Minnesota Impulse Disorders Interview (mMIDI) unless a structured clinical interview performed during Screening confirms that the patient does not have an ICD.
20. Patient is currently lactating or pregnant or planning to become pregnant during the duration of the study.
21. Patient has a known hypersensitivity to any components of the IMP or excipients.
22. Any other condition or clinically significant abnormal findings on the physical or neurological examination, psychiatric and m

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Parkinson's Disease
MedDRA version: 19.1 Level: LLT Classification code 10013113 Term: Disease Parkinson's System Organ Class: 100000004852

Intervention(s)

Product Name: tozadenant
Product Code: TOZ
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: tozadenant
CAS Number: 870070-55-6
Current Sponsor code: TOZ
Other descriptive name: TOZADENANT
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 60-

Primary Outcome(s)

Main Objective: To evaluate the safety and tolerability of tozadenant in levodopa-treated PD patients experiencing motor fluctuations

Primary end point(s): 1. Treatment emergent Adverse Events.
2. Vital signs
3. ECGs
4. Clinical Laboratory tests
5. Physical and neurological examinations

Timepoint(s) of evaluation of this end point: End of treatment, assumed to be 52 weeks

Secondary Objective: To evaluate the effects of tozadenant on the occurrence of daytime drowsiness, impulsive behavior, and suicidality.

Secondary Outcome(s)

Secondary end point(s): Epworth Sleepiness Scale ESS
modified Minnesota Impulse Disorders Interview mMIDI
Columbia Suicide Severity Rating Scale C-SSRS
Unified Parkinson’s Disease Rating Scale (UPDRS) Part I - IV
Clinical Global Impression of Change (CGI-C).
Patient’s Global Impression of Change (PGI-C).
Parkinson’s Disease Quality of Life Questionnaire (PDQ-39; total score and individual domain scores).
Non-motor Symptom Questionnaire.
EuroQol 5D-5L Health Questionnaire (EQ-5D-5L).
Patient-completed diaries (Change from Baseline in the number of hours per day spent as follows: OFF time, ON time without troublesome dyskinesia, total ON time, ON time with troublesome dyskinesia and asleep time).
Healthcare Resource Utilization.

Timepoint(s) of evaluation of this end point: End of treatment, assumed to be 52 weeks

Secondary ID(s)

78230

TOZ-CL06

Source(s) of Monetary Support

Biotie Therapies