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.

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.