None listed
Conditions
Brief summary
The purpose of this study is to determine if up to 4 weeks of once weekly oral dosing of RTB101 and sirolimus given alone or in combination is safe, tolerable and achieves potentially therapeutic exposures in the CNS (central nervous system) of patients with mild (modified Hoehn and Yahr [mH&Y] stage less than or equal to 2) Parkinson’s disease (PD)
Interventions
• 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 assess
• 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.
Sponsors
resTORbio, Inc.
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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. • Treated breast cancer localized to the breast. -Patients with clinically significant underlying pulmonary disease other than asthma. The following cardiac conditions: a) Unstable angina pectoris or acute ischemic changes on ECG at Screening. b) History of myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI) within 6 months prior to Screening. c) Ventricular arrhythmias except for benign premature ventricular contractions. d) New York Heart Association functional classification III-IV congestive heart failure. - Any other medical condition, as judged by the Investigator, that is likely to interfere with the patient’s participation in the study, or likely to cause serious adverse events (SAEs) during the study.
Outcome results
None listed