A Phase 2 Study of CX-8998 in Adults With Tremor Associated With Parkinson's Disease

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of CX-8998 for Tremor Associated With Parkinson's Disease

This is a Phase 2, multicenter, double-blind, placebo-controlled, parallel-group study consisting of a screening period of up to 4 weeks, a 4 week randomized double-blind, dose-titration treatment period, followed by a 1 week safety follow-up period after the last dose of study medication, and a scheduled follow-up safety telephone call one week later.

This is a Phase 2, multicenter, double-blind, placebo-controlled, parallel-group study consisting of a screening period of up to 4 weeks, a 4 week randomized double-blind, dose-titration treatment period, followed by a 1 week safety follow-up period after the last dose of study medication, and a scheduled follow-up safety telephone call one week later.

Subjects will be randomized 1:1 to one of two treatment groups. Group A will receive titrating doses of CX-8998 up to 10 mg BID and Group B will receive placebo.

Subjects will participate for a total of up to 12 weeks, including screening, the 4-week treatment period and follow-up.

Inclusion Criteria:

• Men or non-pregnant, non-breastfeeding women 40 to 80 years-of-age who are able to read and understand English.
• Mini Mental State Exam (MMSE) score ≥ 24.
• Clinical diagnosis of idiopathic Parkinson's disease and presence of at least 2 out of 3 cardinal characteristics (tremor, rigidity, and/or bradykinesia).
• Hoehn & Yahr Stage I III (inclusive) if not experiencing motor fluctuations. If experiencing motor fluctuations, must be Hoehn & Yahr Stage I IV (inclusive) when OFF or I-III (inclusive) when ON.
• An MDS-UPDRS tremor score (sum of items 2.10, 3.15, 3.16, 3.17, 3.18) of a least 10 (during ON for subjects experiencing fluctuations) (centrally rated) (Forjaz et al., 2015). A limited number of subjects with an MDS-UPDRS of 8 or 9 may be included with Sponsor approval.
• Treated with a stable regimen of anti-parkinsonian and/or anti-tremor medication (with the exception of primidone) for at least 2 weeks prior to screening. Changes to anti-parkinsonian or anti-tremor medications after screening is not permitted.

Exclusion Criteria:

• Current diagnosis of: a. essential tremor / b. cerebellar disease
• Presence or known history of: a. significant visual hallucinations (in the opinion of the Investigator and/or Study Safety Representative) / b. significant impulse control disorder (ICD) (in the opinion of the Investigator and/or Study Safety Representative).
• History or clinical features consistent with an atypical parkinsonian syndrome.
• Dyskinesia or dystonia that would, in the opinion of the investigator, central rater, or Sponsor, interfere with the assessment of tremor.
• Exposure to tremorigenic drugs or drug withdrawal states within the 30 days prior to the first planned dose of study drug.
• Direct or indirect trauma to the nervous system within 3 months preceding the onset of tremor.
• History or clinical evidence of psychogenic tremor origin. Known history of other medical or neurological conditions that may cause or explain subject's tremor.
• Prior MR-guided Focused Ultrasound or surgical intervention (e.g., deep brain stimulation, ablative thalamotomy or gamma knife thalamotomy) for treatment of tremor or Parkinson's disease.
• Use of medication(s) in the past month that might produce tremor or interfere with the evaluation of tremor.
• Inability to refrain from use of medication/substance(s) that might produce tremor or interfere with the evaluation of tremor on study visit days.
• Positive urine drug screen for drugs of abuse, except if this is explained by use of an allowed prescription medicine.
• Regular use of more than two units of alcohol per day.
• Use of prescription or non-prescription drugs or other products (i.e. grapefruit juice) known to be strong inhibitors or inducers of CYP3A4 which cannot be discontinued 2 weeks prior to Day 1 of dosing and withheld throughout the study.
• Concurrent illnesses that would be a contraindication to trial participation.
• Psychological, social, familial, or geographical reasons that would hinder or prevent compliance with the requirements of the protocol or compromise the informed consent process.
• Any other condition and/or situation that causes the Investigator or Study Safety Representative to deem a subject unsuitable for the study (e.g., due to expected study medication non-compliance, inability to medically tolerate the study procedures, or a subject's unwillingness to comply with study-related procedures).
• Treatment with an investigational agent within 30 days prior to the first dose of CX-8998 or planning to receive an investigational agent during the study.