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

• Register: EUCTR
• Last refreshed on: 25 May 2020
• Main ID: EUCTR2017-000135-14-AT
• Date of registration: 08/03/2017
• Prospective Registration: Yes
• Primary sponsor: Prexton Therapeutics B.V.
• Public title: 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
• Scientific title: A Multi-centre, Double-blind, Randomised, Placebo-controlled, Parallel-arm Phase IIa Trial to Evaluate the Efficacy, Safety and Tolerability of 28-Day Oral Treatment with PXT002331 (foliglurax) in Reducing Motor Complications of Levodopa Therapy in Subjects with Parkinson’s Disease Experiencing End-of-dose Wearing Off and Levodopa-Induced Dyskinesia (AMBLED) - AMBLED Study
• Date of first enrolment: 26/05/2017
• Target sample size: 165
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000135-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Germany, Spain, United Kingdom

Contacts

• Name: Lundbeck Clinical Trials
• Affiliation: H.Lundbeck A/S

• Name: Lundbeck Clinical Trials
• Affiliation: H.Lundbeck A/S

Key inclusion & exclusion criteria

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. Additionally, subjects must be co
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 agree to use a barrier method of co

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

Health Condition(s) or Problem(s) studied

Parkinson’s Disease
MedDRA version: 20.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders

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

Intervention(s)

Product Name: foliglurax
Product Code: PXT002331
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: foliglurax
CAS Number: 1883329-52-9
Current Sponsor code: PXT002331
Other descriptive name: CVD00118-E
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: foliglurax
Product Code: PXT002331
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: foliglurax
CAS Number: 1883329-52-9
Current Sponsor code: PXT002331
Other descriptive name: CVD00118-E
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

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
Baseline to Day 28

Secondary Objective: To assess the effects of 2 doses of PXT002331 as an adjunct to levodopa on LID in subjects with PD.

To assess the pharmacokinetic profile of PXT002331 in subjects with PD.

To assess the safety and tolerability of 2 doses of PXT002331 in subjects with PD.

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 Outcome(s)

Secondary end point(s): • Change from baseline to end of Treatment Period (Day 28) in the total objective score (Parts 3 and 4) for dyskinesia impairment and disability assessed by Unified Dyskinesia Rating Scale (UDysRS)

• Change from baseline to end of Treatment Period (Day 28) in UDysRS total score

• Proportion of subjects achieving a clinically significant reduction in OFF time (at least 1 hour as defined by Hauser et al.15) from baseline to end of Treatment Period (Day 28) based on subject Hauser diary entries (average of 3 consecutive days)

• Change from baseline to end of Treatment Period (Day 28) in the percentage of daily awake OFF time based on subject Hauser diary entries (average of 3 consecutive days)

• Change from baseline to end of Treatment Period (Day 28) in the daily awake ON time without troublesome dyskinesia (defined as ON time without dyskinesia plus ON time with non-troublesome dyskinesia) based on subject Hauser diary entries (average of 3 consecutive days)

• Change from baseline to end of Treatment Period (Day 28) in the percentage of daily awake ON time without troublesome dyskinesia (defined as ON time without dyskinesia plus ON time with non-troublesome dyskinesia) based on subject Hauser diary entries (average of 3 consecutive days)

Timepoint(s) of evaluation of this end point: • Baseline to Day 14
• Baseline to end of Treatment Period (Day 28)

Secondary ID(s)

PXT-CL17-001

Source(s) of Monetary Support

Prexton Therapeutics SA

Ethics review

Status: Approved
Approval date: 26/05/2017
Contact: