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