Phase 1b study to determine the safety, tolerability and pharmacokinetics ofRTB101 and sirolimus alone or in combination in patients with Mild Parkinson’s Disease (PD).

Phase 1

Recruiting

• Conditions: Parkinson's disease; Neurological - Parkinson's disease

• Registration Number: ACTRN12619000372189
• Lead Sponsor: resTORbio, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-03-11
• Last Update Posted: 16 September 2019

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 60

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 temperature between 35.0-37.5°C
• Systolic BP, 90-160 mm Hg
• Diastolic BP, 50-95 mm Hg
• Heart rate, 40-95 bpm

Exclusion Criteria

-Parkinsonism due to drug(s) or toxin(s) or with history of a prior brain
magnetic resonance imaging (MRI) without contrast, showing a structural
abnormality that is a possible cause of their PD signs or symptoms
-Patients with prior surgical history of deep brain stimulation (DBS).
-If female, pregnancy (defined as positive beta-human chorionic
gonadotrophin [b-hCG] blood test), lactating or breast-feeding.
-Women of childbearing potential (any woman physiologically capable of
becoming pregnant) unless they remain on highly effective methods of
contraception (see below) throughout the study and for 12 weeks
following discontinuation of the study drug.
-Sexually active male patients with a partner of childbearing
potential must be willing to wear a condom while on study drug
and for 12 weeks after stopping study drug and should not father a child
in this period. A condom is required to be used also by vasectomized men
with a partner of child-bearing potential in order to prevent delivery of
the drug via seminal fluid.
-Use of other investigational drugs within 5 half-lives of randomization, or
within 30 days, whichever is longer; or longer if required by local
regulations.
-History of hypersensitivity or allergy to sirolimus, RTB101 or their
excipients or to other mTOR inhibitor drugs.
-Concomitant use of any of the drugs (including strong CYP3A4 inhibitors or inducers, angiotensin-converting-enzyme (ACE) inhibitors, anti-coagulants) or other treatments (including live vaccines)
-Any one of the following hematologic or coagulation abnormalities at
screening:
• Haemoglobin <10.0 g/dL for males and <9.0 g/dL for females
• White blood cell count (WBC) <3,500/mm3
• Neutrophil count <2,000/mm3
• Platelet count <125,000/mm3
• International normalized ratio (INR) >1.2
• Partial prothromboplastin time (PTT) >35 seconds.
-Patients receiving immunosuppressive therapy including chronic use of
prednisone >10 mg daily.
- Patients with active or chronic infection other than fungal skin or nail infection or local herpes simplex infection.
-Immunodeficiency diseases, including a positive human immunodeficiency virus (HIV) test result; or chronic infection with Hepatitis B virus (HBV) or Hepatitis C virus (HCV).
-Recent surgery (involving entry into a body cavity or requiring sutures) within 2 months of the Screening Visit or any evidence of unhealed surgical wound or lack of significant recovery from the surgery (minor skin surgery is allowed within 2 months of Screening provided the surgical wound has healed).
-Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the patient in case of participation in the study.
-Patients with insulin-dependent diabetes mellitus (Type 1 or 2)
-Patients with significant uncontrolled hypercholesterolemia
-History of malignancy in any organ system, treated or untreated, within the past 3 years, regardless if there is evidence of local recurrence or metastases, except for localized basal cell or squamous cell carcinoma of the skin. History of malignancy in any organ system, treated or untreated, within the past 3 years, regardless if there is evidence of local recurrence or metastases, except for:
• Treated localized basal cell carcinoma of the skin.
• Prostate cancer confined to the gland (AJCC stage T2N0M0 or better).
• Treated cervical carcinoma in situ.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Percentage of patients experiencing one or more treatment-emergent adverse events in the treatment arms compared to the placebo arms.<br>Adverse events that may occur: diarrhoea, nausea, abdominal discomfort, oral discomfort, abdominal pain, flatulence, regurgitation, vomiting, headache.<br>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.];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.]

Secondary Outcome Measures

Name	Time	Method
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];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)]