| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Early-Stage Parkinson’s Disease |
|
| E.1.1.1 | Medical condition in easily understood language |
Early-Stage Parkinson’s Disease
|
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 15.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061536 |
| E.1.2 | Term | Parkinson's disease |
| E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To determine whether PYM50028 exhibits clinical benefit in the treatment of subjects with early-stage Parkinson’s disease (PD), as assessed by the Unified Parkinson’s Disease Rating Scale score for Parts II and III combined (UPDRS II/III), compared with placebo. |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the efficacy of PYM50028 compared with placebo on other aspects of PD and to assess safety, tolerability and plasma concentration of PYM50028 in the treatment of early-stage PD. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subjects must provide written informed consent prior to any study procedures being performed.
2. Subjects must be able to understand the study requirements and be able and willing to follow any instructions and comply with all scheduled study visits.
3. Male or female subjects aged between 35 and 75 years, inclusive at the time of consent.
4. Subjects must have a confirmed diagnosis of early-stage idiopathic PD according to the UK PD Society Brain Bank (UKPDSBB) criteria within the 2 years prior to screening.
5. Subjects must have a Hoehn and Yahr Score of 1 to 2.5, inclusive and no postural instability.
6. Subjects whose clinical condition at the time of study enrolment does not require any PD therapy and, to the investigator's best judgment, will not require such therapy for the next 6 months.
7. Female subjects must be of non-child bearing potential: post-menopausal (no menses in the past 12 months and follicle stimulating hormone [FSH] levels > 40 IU/L), hysterectomised or surgically sterilised.
8. Male subjects must agree to use two medically acceptable methods of contraception (e.g., double barrier) throughout the study and for 1 month after completing dosing with IMP.
9. Subjects must have liver enzymes (aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), gamma glutamyltransferase (GGT/γGT), alkaline phosphatase (ALP)) that are lower than or equal to 1.5 times the upper limit of normal (ULN) and total bilirubin (TBL) values that are lower than or equal to the ULN.
10. Subjects must be in good health, with no clinically significant and relevant medical history that could affect the conduct of the study and evaluation of the data, as ascertained by the investigator through detailed medical history and screening assessments. |
|
| E.4 | Principal exclusion criteria |
1. Subjects with a diagnosis of atypical Parkinsonism or any known secondary Parkinsonian syndrome.
2. Subject has a history of pallidotomy, thalamotomy, deep brain stimulation or foetal tissue transplant or any other neurosurgical procedure.
3. Subjects with any current or past (in the last 12 months) psychiatric diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, text revision (DSM-IV-TR) that might interfere with the subject’s ability to perform the study and the required study assessments. This would include alcohol- and drug-related abuse or dependence, dementia (assessed as a mini mental state examination [MMSE] score of < 24), major depression (assessed as BDI-II score ≥ 15), schizophrenia, bipolar disorder and mental retardation. Mild depression, anxiety and related disorders would be acceptable, providing they are controlled, any drug treatment (excluding anti-psychotics) has been stable for 4 weeks prior to screening and is expected to remain stable for the duration of the study.
4. Subjects currently taking any treatment for PD, including, but not limited to, L DOPA, catechol-O-methyl transferase (COMT) inhibitors, non-selective monoamine oxidase (MAO) inhibitors, MAO-B inhibitors, dopamine agonists, anti-cholinergics and apomorphine (see also section 8.1). Subjects that have previously taken any medicinal treatment for PD for a total period not exceeding 4 weeks AND have not taken any medicinal treatment for PD within the 8 weeks prior to screening can be included in the study.
5. Exclusion criterion not applicable
6. Subjects receiving concomitant therapy with any of the following medications: St John’s Wort, digoxin, warfarin or heparin or have received such medications within 4 weeks prior to screening.
7. Subjects with a current or past (in the last 12 months) history of seizure or epilepsy or unexplained loss of consciousness.
8. Female subjects who are breast feeding, pregnant, or intending to become pregnant; male subjects whose partner is intending to become pregnant.
9. Treatment with any IMP (with the exception of Coenzyme Q10) within 12 weeks prior to the screening visit or the equivalent time of six half-lives of the IMP, whichever is longer; a 4-week washout is required for subjects who have taken Coenzyme Q10 as an IMP.
10. Subjects without a gall bladder.
11. Intention to donate blood or plasma during the study or in the 8 weeks after the final dose of IMP.
12. A medical history of infection with human immunodeficiency virus, hepatitis C and/or hepatitis B.
13. A history of malignancy of any type, other than surgically excised non melanoma skin cancers, within 5 years prior to screening.
14. Subjects with poorly controlled insulin dependent or non-insulin dependent diabetes mellitus.
15. Subjects who are following a diet that severely restricts carbohydrate intake (ketogenic diets).
16. Subjects who are currently taking medium chain triglycerides (MCT) as a dietary supplement or for any other reason.
17. Any relevant condition, behaviour, laboratory value or concomitant medication which, in the opinion of the investigator, makes the subject unsuitable for entry into the study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint of this study is the change in UPDRS II/III score between baseline and Week 28. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Assess any dose-response relationship; time to symptomatic PD therapy;
change in SCOPA-COG total score between baseline and Week 28;
change in PDQ-39 scores for each domain and total score between
baseline and Weeks 12 and 28;
change in ESS total score between baseline and Week 28;
change in NMSS scores for each domain and total score between
baseline and Week 28. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 56 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| Czech Republic |
| France |
| Germany |
| Hungary |
| Poland |
| Romania |
| Serbia |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end of the study will be the date of the last subject’s last visit. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 15 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 15 |
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