To Assess the Efficacy and Safety of Ceftriaxone in Patients With Mild to Moderate Parkinson's Disease Dementia

• Register: ClinicalTrials.gov
• Last refreshed on: 23 October 2023
• Main ID: NCT03413384
• Date of registration: 08/01/2018
• Prospective Registration: Yes
• Primary sponsor: BrainX Corporation
• Public title: To Assess the Efficacy and Safety of Ceftriaxone in Patients With Mild to Moderate Parkinson's Disease Dementia
• Scientific title: A Randomized, Double Blinded, Placebo-controlled Phase II Study to Assess the Efficacy and Safety of Ceftriaxone in Patients With Mild to Moderate Parkinson's Disease Dementia
• Date of first enrolment: February 15, 2019
• Target sample size: 106
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03413384
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

Taiwan

Contacts

• Name: Andrew Liu

• Name: Joshua Ho
• Affiliation: China Medical University, China

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Patients are male or female, age 50-85 years, inclusive.

2. Diagnosis of idiopathic Parkinson's disease (PD) based on the UK Parkinson's Disease
Society Brain Bank Criteria and with a modified Hoehn and Yahr Stage of I to IV.

3. Patients have been receiving stable dose of medications equivalent up to 1800 mg/day
of levodopa for Parkinson's disease at least 2 weeks prior to screening and patients
are considered as being optimally treated at screening and no known further
adjustments of current medication needed to improve the subject's status of PD during
the study period by the judgment of the Investigator based on the subject's history,
previous treatments, and the clinical presentation.

4. Diagnosis of PDD based on Movement Disorder Society (MDS) Task Force criteria as the
following items:

1. A diagnosis of PD based on UK Parkinson's Disease Society Brain Bank Criteria

2. PD development prior to the onset of dementia based on patient/caregiver history
or records

3. Cognitive deficiency severe enough to impair daily life based on
patient/caregiver interview or questionnaire

4. Impairment of at least 2 of the following domains: attention, executive function,
visuo-constructive ability, memory Besides, patients' Mini-Mental State
Examination (MMSE) should be in the range of 18-25 (inclusive) or CDR scale in
the range of 0.5-2. Note that MMSE range 16-25 for illiterate. Illiterate is
defined as no education history.

5. Patients who are eligible and able to participate in the study must be judged by the
investigator to evaluate the competency of providing informed consent for this
dementia related study (the decision making is based on MacArthur Competence
Assessment concept) and should be able to understand the language in which the tests
require so and must be able to perform all the assessments.

6. All male and female patients with child-bearing potential (between puberty and 2 years
after menopause) should use at least any one of the appropriate contraception methods
shown below, for during and at least 4 weeks after ceftriaxone treatment.

1. Total abstinence (when this is in line with the preferred and usual lifestyle of
the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception).

2. Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy) or tubal ligation at least six weeks before taking study treatment.
In case of oophorectomy alone, only when the reproductive status of the woman has
been confirmed by follow up hormone level assessment.

3. Male sterilization (at least 6 months prior to screening). For female subjects on
the study, the vasectomized male partner should be the sole partner for that
subject

4. Combination of any two of the following listed methods: (d.1+d.2 or d.1+d.3, or
d.2+d.3):

d.1 Use of oral, injected or implanted hormonal methods of contraception or other
forms of hormonal contraception that have comparable efficacy (failure rate <1%), for
example hormone vaginal ring or transdermal hormone contraception.

d.2 Placement of an intrauterine device (IUD) or intrauterine system (IUS). d.3
Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault
caps) with spermicidal foam/gel/film/cream/vaginal suppository.

Exclusion Criteria:

1. Any indication of forms of Parkinsonism other than idiopathic PD.

2. Diagnosis of possible PDD.

3. Diagnosis of dementia with Lewy Bodies.

4. Mental/physical/social condition which could preclude performing efficacy or safety
assessments.

5. Medical history of brain or other clinically significant neurological/psychiatric
disorders or injuries other than PD or PDD that would hinder or interfere the study
safety or efficacy evaluation in the opinion of the Investigator.

6. The patients have received neurosurgical intervention related to PD (e.g. deep brain
stimulation (DBS), thalamotomy etc.) or are scheduled to do so during the trial
period.

7. The patients have history of allergic response to levodopa, ceftriaxone, cephalosporin
class of drugs or ursodiol or lidocaine.

8. Malignant neoplastic disease, either currently active or in remission for less than 1
year.

9. Clinically significant and unstable gastrointestinal, renal, endocrine, pulmonary, or
cardiovascular disease, including not well controlled hypertension, asthma, chronic
obstructive pulmonary disease, diabetes, hyperbilirubinemia, impaired vitamin K
synthesis or low vitamin K stores that would hinder or interfere participation to the
study in the opinion of the Investigator.

10. Patients with abdominal ultrasound examination imaging shows active biliary
obstruction disease at PI's discretion during screening.

11. The patients are currently experiencing unpredictable or intractable or troublesome
dyskinesia or fluctuations in their symptoms.

12. Patients with the following medications that could put patients at risk, interfere
with study evaluations, or prevent meeting the requirements of the study at the
judgement of PI should be excluded :

1. Centrally acting anticholinergic medication currently or within 4 weeks prior to
the screening visit.

2. Cocaine, opioids, ethanol (binge drinking or heavy alcohol defined by SAMHSA and
NIAAA) currently or within 4 weeks prior to the screening visit; amphetamines,
cannabinoids abuse history or taking currently or within 3 months prior to the
screening visit.

3. Acetylcholinesterase inhibitors or memantine currently or within 4 weeks prior to
the screening visit, except that patients have been stable controlled and have
been receiving stable dose of the acetylcholinesterase inhibitors or memantine
for at least 4 weeks prior to screening or are considered being optimally treated
at screening without further dose adjustments needed as judged by the
Investigator.

4. Ceftriaxone or cephalosporin or penicillin or ß-lactam currently or within 4
weeks prior to the screening visit.

5. Neuroleptics or antipsychotics for treatment of psychotic symptoms (e.g.,
hallucinations) within 4 weeks prior to the screening visit, exc


Age minimum: 50 Years
Age maximum: 85 Years
Gender: All

Health Condition(s) or Problem(s) studied

Parkinson's Disease Dementia

Intervention(s)

Other: Placebo

Drug: Ceftriaxone

Primary Outcome(s)

Compare the treatment difference in mean net change in ADAS-Cog score with time course [Time Frame: from baseline to week 17 and 33 visits]

Secondary Outcome(s)

Changes in Mini-Mental State Examination (MMSE) score [Time Frame: from baseline at week 17 and 33 visits]

Changes in MRI image for atrophy rate of brain [Time Frame: from baseline to week 17 and 33 visits]

Changes in MRI image for dopaminergic projection from substantia nigra to striatum [Time Frame: from baseline to week 17 and 33 visits]

Changes in Clinical Dementia Rating (CDR) Scale score [Time Frame: from baseline to week 17 and 33 visits]

Changes in Color Trail Test score [Time Frame: from baseline to week 17 and 33 visits]

Changes in Judgment of Line Orientation score [Time Frame: from baseline to week 17 and 33 visits]

Changes in Unified Parkinson's Disease Rating Scale (UPDRS) score [Time Frame: from baseline to week 17 and 33 visits]

Changes in Tc-99m TRODAT SPECT image [Time Frame: from baseline to week 17 and 33 visits]

Secondary ID(s)

BRICEFA20170414

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Virginia Contract Research Organization Co., Ltd.