Clinical trial NCT03436953: A Phase 2 Study of CX-8998 in Adults With Tremor Associated With Parkinson's Disease
Official title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of CX-8998 for Tremor Associated With Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Parkinson's Disease
Tremor
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-02-19
Enrollment: 0
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from Baseline to Day 28 on the MDS-UPDRS Tremor Score as scored by the central rater
timeFrame: Baseline through completion of study treatment period, an average of 28 days
Secondary outcomes:
measure: Change from Baseline to Day 28 on the TETRAS Activity of Daily Living subscale
timeFrame: Baseline through completion of study treatment period, an average of 28 days
measure: Change from Baseline to Day 28 in accelerometry score
timeFrame: Baseline through completion of study treatment period, an average of 28 days
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] as assessed by CTCAE v4.0
timeFrame: Through study completion, an average of 12 weeks
measure: Changes from baseline in QTcF
timeFrame: Baseline through study completion, an average of 5 weeks
measure: Percentage of subjects who did not complete the study due to Treatment Emergent Adverse Events as assessed by CTCAE v4.0
timeFrame: Duration of study, an average of 12 weeks
measure: Percentage of subjects with Serious Adverse Events as assessed by CTCAE v4.0
timeFrame: Duration of study, an average of 12 weeks
measure: Percentage of subjects with Adverse Events of Special Interest as assessed by CTCAE v4.0
timeFrame: Duration of study, an average of 12 weeks
measure: Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Screening through study completion, an average of 8 weeks
measure: Epworth Sleepiness Scale
timeFrame: Baseline through completion of study treatment period, an average of 28 days
measure: Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS)
timeFrame: Screening through study completion, an average of 8 weeks
measure: University of Miami Parkinson's disease Hallucinations Questionnaire (UM-PDHQ)
timeFrame: Screening, Baseline and Day 28, an average of 28 days
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: Screening and Day 28, an average of 28 days
Other outcomes:
Locations:
Study officials:
affiliation: Jazz Pharmaceuticals
name: Stacey Boyer, PhD
role: STUDY_DIRECTOR
References: