Parkinson´s disease inadequately controlled on a stable regimen of anti-Parkinsonian medications. MedDRA version: 12.0 Level: LLT Classification code 10013113 Term: Disease Parkinson's
Conditions
Interventions
Trade Name: Orfadin
Pharmaceutical Form: Capsule*
INN or Proposed INN: NITISINONE
CAS Number: 104206-65-7
Current Sponsor code: SYN118
Concentration unit: mg milligram(s)
Concentration type: equal
Con
Sponsors
Synosia Therapeutics AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female subjects with a confirmed diagnosis of idiopathic Parkinson?s disease (PD), meeting the UK Parkinson?s Disease Society Brain Bank diagnostic criteria [Daniel et al., 1993], of a greater than 1 year duration, who are otherwise healthy and fulfill all of the inclusion criteria and none of the exclusion criteria. 2. Age range 40 – 85 years. 3. Modified Hoehn and Yahr Stage 2-4. 4. Subjects in the “fluctuating” stage of PD with an average of at least 2 hours and no more than 6 hours “off” time during awake hours from the 24-hour patient diaries taken during the 2 consecutive days directly preceding the scheduled Baseline/Day 1 visit. 5. Subjects who have been levodopa-responsive for at least 1 year and taking at least 4 doses per day (or at least 3 doses per day if 2 or more are a sustained-release formulation). Note: Combination products containing levodopa and levodopa/carbidopa with a COMT inhibitor in one fixed dosage form (Stalevo®) are permitted. 6. If receiving allowed anti-Parkinson?s medication(s) other than levodopa, subjects must have been clinically stable on the same dose for a minimum of 30 days before randomization. 7. A Unified Parkinson?s Disease Rating Scale (UPDRS) III Motor Examination score greater than 25 in defined “off” state at the screening and baseline assessment. 8. Mini-mental state examination (MMSE) score greater than 24 to rule out dementia. 9. Good general health, free from significant co-morbid illnesses that could interfere with evaluation of study drug, as ascertained by detailed medical history and physical and laboratory examinations. 10. Able to provide and have signed an Institutional Review Board/Independent Ethics Committee-approved written informed consent form to participate in this study. 11. Plasma creatinine less than or equal to 2.2 mg/dL or 194 µmol/L. 12. Women with no childbearing potential; ie, woman who are surgically sterile or woman who have been post-menopausal for at least 1 year as confirmed by follicle-stimulating hormone (FSH) greater than or equal to 40 mIU/mL or 40 IU/L. Men who have a sterile or post-menopausal sexual partner or have agreed to use contraception (eg, use of a condom with spermicide or use by partner of oral, implantable or injectable contraceptives, intrauterine device [IUD], diaphragm with spermicide), starting at the time of study drug administration and for a period of 1 month after the end of the study. 13. Achieved the following results for PD diary training and baseline diary recordings: a. Completed the protocol-specified diary training during the screening period and achieved at least 75% diary concordance with the site trainer/rater. b. Returned diary recordings for the 2 consecutive days (ie, 2 consecutive 24-hour periods) directly preceding the Baseline/Day 1 visit that have not more than 4 invalid entries per 24-hour period. An invalid diary entry is defined as more than 1 entry recorded in a given half-hour interval or the absence of an entry in a given half-hour interval. Note: Subjects who are otherwise eligible but do not meet the criteria for proper diary completion may be retrained and can return for another baseline assessment within the 3-week window of the screening period. 14. Able to understand study requirements and able and willing to follow instructions, attend all required study visits, and undergo all planned tests. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years
Exclusion criteria
Exclusion criteria: 1. Atypical or secondary parkinsonism. 2. Prior neurosurgical operation for Parkinson?s disease (PD). 3. Subjects being treated concomitantly with both a COMT and a MAO-B inhibitor. 4. Subjects taking or requiring adjunctive therapy for Parkinson?s disease (PD) with apomorphine. 5. Subjects treated with intraduodenal preparations of levodopa (eg, Duodopa) or with intradermal levodopa delivered with a pump. 6. Subjects with a dyskinesia score of 3 or 4 on UPDRS subscale IV, Item 33 at the screening or baseline assessment; peak-dose dyskinesia will not exclude otherwise eligible subjects. 7. Any 12-lead ECG with any of the following abnormalities at screening: 2nd or 3rd degree heart block, conduction disorders, ventricular and/or atrial arrhythmias; (1st degree bradycardia: non-specific ST and T wave changes are acceptable if reviewed, approved and documented as not clinically significant [NCS] by the Investigator). 8. Subjects with active ocular disease (not including cataracts) including but not limited to: infection, inflammation, macular degeneration, optic nerve degeneration. 9. History of conjunctivitis, corneal opacity, keratitis, photophobia, or blepharitis in the past 2 years. 10. Subjects who have been diagnosed and/or require therapy to treat a psychiatric disorder other than depression including but not limited to Parkinson?s dementia or drug induced hallucinations/paranoia, dementia, schizophrenia or bipolar disorder. 11. Geriatric Depression Scale (short form) score greater than 8. 12. Subjects receiving treatment for depression with antidepressants if they have not been on a stable dose for 30 days prior to randomization. 13. Any other condition or clinically significant abnormal findings on the physical or neurological examination (eg, multiple system atrophy, recent stroke), medical and psychiatric history, or clinical laboratory results at screening that, in the opinion of the Investigator, make the subject unsuitable for the study or put the subject at additional risk. 14. Potential exposure to SYN118 (Orfadin®, nitisinone) outside the context of the present trial. 15. Subjects who require drugs that are inducers of the P450 CYP3A4 isoenzyme including, HIV antivirals (efavirenz, nevirapine), barbiturates, carbamazepine, glucocorticoids, modafinil, phenobarbital, phenytoin, rifampin, St. John's wort, troglitazone, oxcarbazepine, pioglitazone, rifabutin. The following site may be referred to in determining whether drugs not listed can induce this enzyme: http://medicine.iupui.edu/clinpharm/ddis/table.asp 16. Preparations containing iron and/or amino acids, for example some multi-vitamin/mineral preparations or nutritional supplements. 17. Received treatment with any other investigational drug within 5 half-lives or 30 days prior to signature of informed consent, whichever is longer, or any investigational device within 30 days prior to signature of informed consent. 18. Pregnant or lactating females.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety, tolerability and efficacy of SYN118 when administered to subjects with PD who are inadequately controlled on a stable regimen of anti-Parkinson?s medications.;Secondary Objective: To improve control of PD symptoms for subjects inadequatelly treated with antiparkinsonian medication.;Primary end point(s): This is an exploratory study, no primary endpoints defined. | — |
Countries
Czech Republic, France
Outcome results
None listed