A study to look at how safe, well tolerated, and what effect on the body, study drug PXT002331 has in patients with Parkinson's Disease who are already taking the drug Levodopa

Phase 1

Conditions: Parkinson’s Disease
MedDRA version: 20.0Level: PTClassification code 10061536Term: Parkinson's diseaseSystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2017-000135-14-DE

Lead Sponsor: Prexton Therapeutics B.V.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 165

Inclusion Criteria

1. Subjects will be:
1.1. males or females of non-childbearing potential diagnosed after the age of 30 years with idiopathic PD (ie, not induced by drugs or other diseases) as defined by fulfilling Steps 1 and 2 of the United Kingdom (UK) PD Society Brain Bank clinical diagnostic criteria

1.2. between 35 and 85 years of age, inclusive, at the time of signing informed consent

2. Subjects will have:
2.1. a documented medical history of idiopathic PD for at least 3 years

2.2. disease severity of 2 to 4 on the modified Hoehn and Yahr scale when in the OFF state

2.3. been treated with a stable regimen of levodopa-containing therapy and should maintain the stability of their therapy throughout the study according to their usual regimen (dose level and frequency). The maximum allowed total levodopa dose must be =1600 mg per day.

2.3.1. subjects who are on an immediate-release formulation of levodopa-containing therapy, NOT including Apodespan PR (or equivalent), must be receiving at least 3 doses per day and must be on a stable dose for at least 2 weeks prior to the first screening visit.

2.3.2. subjects who are on a long-acting formulation of levodopa-containing therapy, including Apodespan PR (or equivalent), must be on a stable dose for at least 6 weeks prior to the first screening visit

2.4. experienced motor fluctuations with wearing off over a period of at least 3 months prior to randomisation, with a minimum daily OFF time of at least 2 hours per 24 hours, while awake (as measured during the Screening Period by subject home diary [Hauser diary] on each of the 3 consecutive days immediately preceding the baseline visit; =2 hours OFF time on each of the 3 days)

2.5. experienced predictable OFF periods, as assessed at screening and baseline by a MDS UPDRS Part IV B, Question 4.5 rating of 1 or 2

2.6. experienced LID over a period of at least 3 months prior to randomisation, with a minimum daily ON time with dyskinesia (troublesome and/or non troublesome) lasting at least 2 hours per 24 hours, while awake (as measured during the Screening Period by subject home diary [Hauser diary] on each of the 3 consecutive days immediately preceding the baseline visit; =2 hours ON time with dyskinesia on each of the 3 days)

2.7. experienced significant time spent with LID, as assessed at screening and baseline by MDS UPDRS Part IV A, Question 4.1 score =1

2.8. experienced impact from LID on daily function, as assessed at screening and baseline by MDS UPDRS Part IV A, Question 4.2 score =2

2.9. been on a stable regimen of any additional permitted anti-Parkinsonian drugs (ie, peripheral decarboxylase inhibitors, dopamine agonists [except apomorphine], MAO-B inhibitors [except safinamide] or COMT inhibitors) for at least 4 weeks prior to baseline.

3. Female subjects will be women of non-childbearing potential, defined as follows:
3.1. permanently sterile following hysterectomy, bilateral salpingectomy, bilateral oophorectomy or confirmed tubal occlusion (not tubal ligation)

3.2. postmenopausal, defined as at least 12 months post cessation of menses (without an alternative medical cause)

3.2.1. postmenopausal status will be confirmed with a screening serum follicle stimulating hormone (FSH) level greater than 40 mIU/mL.

4. Subjects must pass a Hauser diary concordance test, defined as at least 75% concordance in ON/OFF ratings between rater and subject over the 4 assessments made over a 2-hour period

Exclusion Criteria

Medical conditions and diagnostic tests:
1. Subjects with atypical, secondary or drug-induced Parkinsonism (eg, metoclopramide, flunarizine), metabolic identified neurogenetic disorders (eg, Wilson’s disease), encephalitis, or Parkinson Plus syndromes, or other forms of atypical Parkinsonian syndromes (eg, progressive supranuclear palsy and multiple system atrophy)
2. Subjects with a Mini-Mental State Examination (MMSE) score <25
3. Subjects who have Long QT syndrome or a QTcF >450 ms (males) or >470 ms (females) that is considered clinically significant by the Investigator at screening or baseline
4. Subjects who have, or who have a history of, any clinically significant hepatic or gallbladder disorder, as determined by the Investigator
5. Subjects who have dementia, currently active psychosis or hallucinations. Previous psychotic episodes that were brief and considered drug-induced are not exclusionary; inclusion of such subjects is at the Investigator’s discretion.
6. Suicide attempt within 1 year prior to the first screening visit, or severe suicidal ideation within 6 months prior to the first screening visit (ie, the subject answers yes” to Questions 4 or 5 in the Baseline/Screening C SSRS assessment performed at the first screening visit), or subject is at significant risk of suicidal behaviour in the opinion of the Investigator
7. Subject has a current diagnosis of epilepsy, has a history of seizures as an adult, has a history of stroke or has had a transient ischemic attack within 1 year prior to the first screening visit
8. Subjects who have a known genetic disorder of human UDP-glucoronosyltransferase
9. Any known contraindication to the use of levodopa, including a history of malignant melanoma or a history of narrow-angle glaucoma
10. Subject has cancer, with the exception of the following: basal cell carcinoma or successfully treated squamous cell carcinoma of the skin; cervical carcinoma in situ; prostatic carcinoma in situ; or other malignancies curatively treated and with no evidence of disease recurrence for at least 3 years
11. Positive serology test (hepatitis B virus surface antigen [HBsAg], hepatitis C virus [HCV] antibody, human immunodeficiency virus [HIV] 1 or 2 antibodies)
12. Subjects who have had a clinically significant illness within 4 weeks of first dose, as determined by the Investigator
13. Subjects with scheduled surgeries during the study period
14. Any advanced, severe or unstable disease (other than PD) that may interfere with the primary and secondary study outcome evaluations

Prior/concomitant medication and surgery:
15. Subjects who have undergone prior neurosurgical operation for PD or transcranial magnetic stimulation

16. Subjects currently taking (or expected to be administered during the course of the study) any of the prohibited medications.

Prior/concurrent clinical study experience:
17. Subjects who are participating in another clinical study (eg, attending follow-up visits) or who have participated in a clinical study involving administration of an investigational drug (new chemical entity) in the past 3 months prior to the baseline visit

18. Subjects who have previously taken part in or withdrawn from this study. Re-screening may be permitted on a case-by-case basis based on approval from the Sponsor. Re-screening may only be
performed once per subject and applies only to screen failures from the study.

Other exclusions:
19. Male subjects who do not agr

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of 2 doses of PXT002331 as an adjunct to levodopa in the reduction of OFF time in subjects with PD.;Secondary Objective: To assess the effects of 2 doses of PXT002331 as an adjunct to levodopa on LID in subjects with PD.<br><br>To assess the pharmacokinetic profile of PXT002331 in subjects with PD.<br><br>To assess the safety and tolerability of 2 doses of PXT002331 in subjects with PD.<br>;Primary end point(s): The primary efficacy outcome measure will be change from baseline to end of Treatment Period (Day 28) in the daily awake OFF time based on subject Hauser diary entries (average of 3 consecutive days).;Timepoint(s) of evaluation of this end point: Baseline to Day 14<br>Baseline to Day 28

Secondary Outcome Measures

Name	Time	Method

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