Dose Escalation Study of Cu(II)ATSM in Parkinson's Disease

Collaborative Medicinal Development

Status and phase

Completed

Phase 1

Conditions

Parkinson Disease

Treatments

Drug: Cu(II)ATSM

Study type

Interventional

Funder types

Industry

Identifiers

NCT03204929

CMD-2016-002

Details and patient eligibility

About

Multicenter, open-label dose-escalation study

Full description

Multicenter, open-label, phase 1 study of Cu(II)ATSM administered orally to patients with early idiopathic Parkinson's disease. The study will be conducted in two phases. In the first phase, dose cohorts of six patients each will receive escalating daily doses of Cu(II)ATSM to establish the recommended phase 2 dose (RP2D). The starting dose will be 12 mg/day, which has been shown to be well tolerated in an ongoing phase 1 pharmacokinetic and dose-finding study of Cu(II)ATSM in patients with ALS (ClinicalTrials.gov identifier NCT02870634). In the second phase of the study, an expansion cohort of 20 patients will be treated at the RP2D to confirm tolerability and assess preliminary evidence of efficacy.

In both the dose escalation and expansion cohorts, once the first 28 days of treatment are completed, at the discretion of the investigator a patient may continue to receive Cu(II)ATSM treatment for a maximum of six 28-day treatment cycles.

Enrollment

31 patients

Sex

All

Ages

30+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Signed informed consent prior to initiation of any study-specific procedures
Early idiopathic Parkinson's disease (PD) with at least two of the cardinal signs of PD (resting tremor, bradykinesia, rigidity, postural instability). If tremor is not present, must have unilateral onset and persistent asymmetry of symptoms.
Hoehn & Yahr stage ≤ 2
First PD motor symptoms occurred ≤ 5 years prior to screening visit
Use of dopaminergic therapy allowed provided dose is stable for at least 8 weeks prior to screening visit
Use of amantadine and/or anticholinergics allowed provided dose is stable for at least 8 weeks prior to screening visit
Use of CNS-acting medications allowed provided dose is stable for at least 4 weeks prior to screening visit
Age ≥ 30 years at time of PD diagnosis
Adequate bone marrow reserve, liver and renal function:

Absolute neutrophil count ≥ 1500/µL; Platelet count ≥ 150,000/µL; Hemoglobin ≥ 11 g/dL; Creatinine clearance ≥ 6- mL/min (Cockroft & Gault formula); ALT and/or AST ≤ 2 x ULN; total bilirubin ≤ 1.5 x ULN; albumin ≥ 2.8 g/dL

Women and men with partners of childbearing potential must take effective contraception while on study and women of childbearing potential must have a negative pregnancy test and be non-lactating at screening

Exclusion criteria

Atypical Parkinsonism
Taking ≥ 3 dopaminergic medications
Exposure to typical or atypical antipsychotics or other dopamine blocking agents within 6 months prior to screening visit
Exposure to any other investigational agent within 6 months or 2 investigational agents within 12 months prior to screening visit
Known immune compromising illness or treatment
History of brain surgery for PD, including deep brain stimulation and stem cell transplants
History of cognitive or neuropsychiatric conditions
Inability to swallow oral medications or presence of a GI disorder (eg, malabsorption) deemed to jeopardize intestinal absorption of study drug
Active GI disease (excluding GERD) within 30 days prior to screening visit
Presence of any of the following clinical conditions:

any significant non-PD CNS disorder; drug abuse or alcoholism; unstable cardiac, pulmonary, renal, hepatic, endocrine or hematologic disease; active infectious disease; AIDS or AIDS-related complex; malignancy within 3 years of screening (other than fully excised non-melanoma skin cancer, cured in situ cervical carcinoma, early stage bladder cancer, or DCIS of breast); psychosis or untreated major depression within 30 days of screening; dementia