Phase 1b study to determine the safety, tolerability and pharmacokinetics of

INTERVENTION: • Cohort 1: RTB101 300 mg capsule given orally once per week for up to 4 weeks. • Cohort 2: Sirolimus 2 mg tablet given orally once per week for up to 4 weeks. • Cohort 3: RTB101 300 mg capsule + sirolimus 2 mg tablet given orally once per week for up to 4 weeks. • Cohort 4: RTB101 300 mg capsule + sirolimus 4 mg tablet given orally once per week for up to 4 weeks. • Cohort 5: RTB101 300 mg capsule + sirolimus 6 mg tablet given orally once per week for up to 4 weeks. Compliance will be assessed by the investigator and/or study personnel at each visit by having patients bring remaining study drug to each visit. The site staff will count the remaining number of capsules and/or tablets and record this information in the CRF. Cohorts 1 and 2 may be enrolled in parallel, and dose escalation Cohorts 3‐5 will enroll sequentially. CONDITION: Neurological ‐ Parkinson's disease Parkinson's disease; ; Parkinson's disease PRIMARY OUTCOME: Clinically significant changes in clinical laboratory values (eg haematology, blood chemistry urinalysis) or other clinical parameters (e.g. vital signs including body temperature, respiratory rate, blood pressure (supine and standing), pulse rate (supine and standing)) from the baseline value.[From the first dose of the study drug (at Day 0 visit) until Week 4 visit.] Percentage of patients experiencing one or more treatment‐emergent adverse events in the treatment arms compared to the placebo arms.; Adverse events that may occur: diarrhoea, nausea, abdominal discomfort, oral discomfort, abdominal pain, flatulence, regurgitation, vomiting, headache.; Adverse events will be reported by patients at study visits.[From the first dose of the study drug (at Day 0 visit) until Week 4 visit.] SECONDARY OUTCOME: CSF concentrations of RTB101 and sirolimus given alone or in combination after oral administration once weekly in PD patients.[At Week 3 (4 hours post dosing)] Drug concentrations in blood and plasma.[Day 0: 1h pre‐dose; 1h, 2h, 4h post dose; Week 1: 8h post dose, Week 2: 24h post dose, Week 3 : 1h pre‐dose; 1h, 2h, 4h post dose; Week 4 ‐ anytime >4 days following last dose at Week 4 visit] INCLUSION CRITERIA: ‐ Patient must be able to communicate well with the Investigator, and to understand and comply with the requirements of the study. ‐ Signed informed consent must be obtained before any study assessment is performed. ‐ Male and female adults 18 years of age and older at the time of informed consent signing ‐ Patients must weigh greater than or equal to 40 kg and less than or equal to 150 kg at Baseline Visit. ‐ Diagnosis of PD with a mH&Y stage of less than or equal to 2 at screening ‐ Stable medication regimen of PD drugs for at least 30 days (at least 60 days for rasagiline) prior to first dose (Day 0, Visit 3). ‐ At screening and baseline, vital signs (systolic and diastolic blood pressure (BP), pulse rate and body temperature) will be assessed in a sitting position after the patient has rested for at least three minutes. Sitting vital signs must be within the following ranges: • Oral or tympanic body tempe