Early Parkinson’s Disease MedDRA version: 20.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Sun Pharma Advanced Research Company (SPARC) Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part 1. The subject has given written informed consent and is willing to participate in the study; 2. Subject is able to understand and comply with all study procedures (requires literacy in available language of all patient-reported outcome measures); 3. Males or females aged = 50 years; 4. Body mass index (BMI) greater than 18.5 kg/m2 and less than 45 kg/m2; 5. Diagnosed with “Clinically Probable PD” according to the MDS clinical diagnostic criteria, with documented diagnosis of PD per treating physician’s records within three years of the Screening visit. Disease severity according to modified Hoehn & Yahr stage = 2; 6. Projected to not require to start dopaminergic therapy within 9 months from Baseline; 7. Female subjects must be not of childbearing potential, e.g., documented evidence that they are surgically sterile (e.g., hysterectomy, partial hysterectomy, bilateral oophorectomy, bilateral tubal ligation), or post-menopausal (at least 12 months since last menses) prior to Screening with serum Follicular Stimulating Hormone (FSH) =40 mIU/mL). 8. Male subjects enrolled in the study should not father a child and are advised to prevent passage of semen to their sexual partner during intercourse using an effective method as judged by the Investigator for the duration of the study and for 3 months after the last dose of study drug; 9. Willingness to undergo lumbar puncture and skin biopsy for future testing of substances related to PD or K0706 target engagement. (For subjects at sites participating in the Biomarker substudy) Part 2: 1. Subject has completed the part 1 of the study. 2. Subject projected not to need dopaminergic treatment except for treatment with Monoamine Oxidase B (MAOB) inhibitors. MAOB inhibitors will be allowed if the patient was already taking the same during part 1 of the study. 3. Subject has received K0706/placebo, as appropriate, within 4 weeks prior to end of part 1 of the study. 4. Male subjects enrolled in the study should not father a child and are advised to prevent passage of semen to their sexual partner during intercourse using an effective method, as judged by the Investigator, for the duration of the study and for 3 months after the last dose of study drug. 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 252 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 252
Exclusion criteria
Exclusion criteria: Part 1:1 Current, or within 60 days of Screening, use of any prescription, investigational, or over the counter medication for the symptomatic treatment of PD or to slow the progression of PD. Treatment with Monoamine Oxidase B (MAOB) inhibitors will be allowed if the dose is stable for at least 30 days prior to Screening and subjects agree to remain on it for the duration of the study; 2.Prior use of dopaminergic therapy for 30 or more days any time in the past; 3.A diagnosis of a significant central or peripheral nervous system disease affecting the subject's cognition or motor function at any time, such as another neurodegenerative disorder, multiple sclerosis or stroke.This does not include transient neurological deficits such as transient ischemic attacks or migraine aura; 4. A diagnosis of a medical condition that could interfere with interpretation of the MDS-UPDRS during the trial; 5. Contraindications to receiving an MRI; 6. Contraindications to receiving a DaT SPECT scan if a new DaT SPECT scan is required for the study; 7. Most recent DaT SPECT scan not compatible with PD (i.e., Scans Without Evidence of Dopaminergic Deficit [SWEDD]) based on a central reading by a study physician; 8. MRI scan of the brain performed after onset of PD suggestive of secondary Parkinsonism; 9. Severe tremors as defined by a score of "severe" on any of the MDSUPDRS Parts 2 or 3 tremor severity (not constancy) items; 10. Montreal cognitive assessment score 450 milliseconds for males and > 470 milliseconds for females; 15.History or presence of any gastrointestinal disorder or malabsorption syndrome, which might affect absorption of study drug; 16.Subject report of recent (within the previous 6-months) illicit drug use (other than marijuana), or intake of alcohol that is excessive in the opinion of the investigator, or positive urine drug screen at Screening; 17.Subject report of use of marijuana within one month of Screening or lack of willines to forgo use of marijuana during the trial; 18.History of surgery within 4 weeks prior to Screening visit or expectation of a planned surgical or invasive diagnostic procedure during the course of the study; 19.Participation in other investigational drug trials within 30 days prior to Screening; 20.Any concomitant medication or medication excluded that could put subject at risk, or interfere with study evaluations (Protocol Section 7.4); 21.Recent use of medications that can cause Parkinsonism and suspicion of the investigator that it could have worsened the subject's Parkinsonism. This includes neuroleptics, some anti-nausea medications and others; 22.Use of medications that affect the dopaminergic system, within 60 days of Screening. This includes stimulants and Monoamine Oxidase A(MAOA) inhibitors (e.g., phenelzine, and tranylcypromine). Note t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Part 1 (Day 0 to Week 40): From Baseline to Week 40 ( parts 2, 3) Part 2 (Weeks 40 to 80): From Week 40 to Week 80.;Main Objective: Part 1 (Day 0 to Week 40): To determine if K0706 reduces the rate of progression of early-stage Parkinson's disease (PD) versus placebo over 40 weeks, as defined by the sum of the MDS-UPDRS (Movement Disorder Society – Unified Parkinson's Disease Rating Scale) Parts 2 and 3 scores. Part 2 (Weeks 40 to 80): To assess the long-term safety/tolerability of K0706 in subjects with early Parkinson's disease;Secondary Objective: Part 1 (Day 0 to Week 40): To determine if K0706 slows early-stage PD progression by increasing the time to significant worsening on the MDSUPDRS Parts 1, 2 and 3 vs placebo. To determine if K0706 delays the initiation of symptomatic medication for PD versus placebo. To evaluate efficacy of K0706 compared to placebo in terms of (HRQoL) as measured by the (EQ-5D-5L). To determine if K0706 slows progression of early-stage PD versus placebo over 40 weeks in terms of overall severity of PD as measured by the (CGIS) scale. To evaluate the effect of K0706 versus placebo on autonomic nervous system dysfunction related to PD as measured by the Scales for Outcome in PD - Autonomic (SCOPA-AUT). To evaluate safety and tolerability of K0706. To evaluate the relationship between plasma and (CSF) concentrations of K0706 and the measures of efficacy and safety. Part 2 (Weeks 40 to 80): To assess the initial and long-term efficacy of K0706 in subjects with early Parkinson's disease.;Primary end point(s): Part 1 (Day 0 to Week 40): Change from Baseline to Week 40 in the sum of MDS-UPDRS Parts 2 and 3. Part 2 (Weeks 40 to 80): Incidence of treatment emergent adverse events. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1 (Day 0 to Week 40): Change in the MDS-UPDRS Parts 1, 2 and 3 separately and in combination, from Baseline to Weeks 8 through 40 Time from Baseline to initiation of symptomatic medication Change in HRQoL using the EQ-5D-5L from Baseline to Week 40Change in CGIS from Baseline to Week 40 Change in the SCOPA-AUT from Baseline to Week 40 Pharmacokinetics – Plasma and CSF levels of K0706 and any relevant metabolites Part 2 (Weeks 40 to 80): _Change from Week 40 (Baseline for Part 2) to Week 76 of the long term extension study in the sum of MDS-UPDRS Parts 2 and 3 _Change from Week 40 (Baseline for part 2) through 76 in MDS-UPDRS Part IA, Part IB, Part I total, Part II total, Part III total and Part III subscores, _Change in total MDS-UPDRS score (sum of Parts I, II and III) from the Week 40 (Baseline for part 2) through 76 _Time from Week 40 (Baseline for Part 2) to initiation of symptomatic medication in the long term extension study;Timepoint(s) of evaluation of this end point: Part 1 (Day 0 to Week 40): Efficacy_from baseline to earlier visits Other_from Baseline to Week 40 Part 2 (Weeks 40 to 80): From Week 40 to Week 80. | — |
Countries
Hungary, India, Poland, Slovakia, Spain, United States
Contacts
Public ContactSponsor represent - Orest Hurko
Sun Pharma Advanced Research Company Limited (SPARC)
Outcome results
None listed