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

NCT03413384 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: BRICEFA20170414
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 6

Brief Summary

This is a randomized, double blinded, placebo-controlled Phase II study to investigate the efficacy and safety of ceftriaxone in patients with mild to moderate Parkinson's disease dementia (PDD).This study will enroll approximately 106 patients to have up to 84 evaluable subjects, and conduct in Chung Shan Medical University Hospital, National Taiwan University Hospital, Kaohsiung Chang Gung Memorial Hospital, China Medical University Hospital, Changhua Christian Hospital, and Taipei Veterans General Hospital.

Conditions

Parkinson's Disease Dementia

Keywords

Parkinson's Disease; Parkinson's Disease Dementia

Outcome Measures

Primary Outcomes (1)

• Compare the treatment difference in mean net change in ADAS-Cog score with time course

  ADAS-Cog is a validated instrument to assess dementia covering memory, orientation, language, praxis and consisting of 11 items. The total possible scores range from 70 (severe impairment) to 0 (no impairment).

  from baseline to week 17 and 33 visits

Secondary Outcomes (8)

• Changes in Unified Parkinson's Disease Rating Scale (UPDRS) score

  from baseline to week 17 and 33 visits

• Changes in Judgment of Line Orientation score

  from baseline to week 17 and 33 visits

• Changes in Mini-Mental State Examination (MMSE) score

  from baseline at week 17 and 33 visits

• Changes in Clinical Dementia Rating (CDR) Scale score

  from baseline to week 17 and 33 visits

• Changes in Color Trail Test score

  from baseline to week 17 and 33 visits

Other Outcomes (2)

• Net change of biomarker α-synuclein data

  from baseline to week 17 and 33 visits

• Net change of biomarker Aβ42 data

  from baseline to week 17 and 33 visits

Study Arms (2)

Ceftriaxone

EXPERIMENTAL

1. Name: Ceftriaxone 2. Dosage form: crystalline powder for intramuscular injection 3. Dose(s): 1 g 4. Dosing schedule: 1 g ceftriaxone with around 2.0 ml of lidocaine solvent per day for Day 1, 3, and 5 per cycle on a 2 weekly cycle

Drug: Ceftriaxone

Placebo

PLACEBO COMPARATOR

same amount volume of placebo will be given on Day 1, Day 3, and Day 5 per cycle on a 2 weekly cycle

Other: Placebo

Interventions

Ceftriaxone DRUG

1 g ceftriaxone per day for Day 1, 3, and 5 per cycle on a 2 weekly cycle

Also known as: Ceftriaxone Sandoz powder for IV Injection

Ceftriaxone

Placebo OTHER

Placebo per day for Day 1, 3, and 5 per cycle on a 2 weekly cycle

Placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients are male or female, age 50-85 years, inclusive.
• 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.
• 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.
• Diagnosis of PDD based on Movement Disorder Society (MDS) Task Force criteria as the following items:
• A diagnosis of PD based on UK Parkinson's Disease Society Brain Bank Criteria
• PD development prior to the onset of dementia based on patient/caregiver history or records
• Cognitive deficiency severe enough to impair daily life based on patient/caregiver interview or questionnaire
• 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.
• 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.
• 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.
• 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).
• 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.
• 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
• 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.

You may not qualify if:

• Any indication of forms of Parkinsonism other than idiopathic PD.
• Diagnosis of possible PDD.
• Diagnosis of dementia with Lewy Bodies.
• Mental/physical/social condition which could preclude performing efficacy or safety assessments.
• 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.
• 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.
• The patients have history of allergic response to levodopa, ceftriaxone, cephalosporin class of drugs or ursodiol or lidocaine.
• Malignant neoplastic disease, either currently active or in remission for less than 1 year.
• 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.
• Patients with abdominal ultrasound examination imaging shows active biliary obstruction disease at PI's discretion during screening.
• The patients are currently experiencing unpredictable or intractable or troublesome dyskinesia or fluctuations in their symptoms.
• 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 :
• Centrally acting anticholinergic medication currently or within 4 weeks prior to the screening visit.
• 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.
• 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.

Sponsors & Collaborators

• BrainX Corporation: lead
• Virginia Contract Research Organization Co., Ltd.: collaborator

Study Sites (6)

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, Kaohsiung, 83301, Taiwan

Location

Chung Shan Medical University Hospital

Taichung, Taichung, 402, Taiwan

Location

China Medical University Hospital

Taichung, Taichung, 404, Taiwan

Location

National Taiwan University Hospital

Taipei, Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital

Taipei, Taipei, 11217, Taiwan

Location

Changhua Christian Hospital

Changhua, 500, Taiwan

Location

Related Publications (1)

• Arlet J. [40 years of the "Revue du Rhumatisme" (1947-1987). Contribution of French rheumatologists to progress in rheumatology]. Rev Rhum Mal Osteoartic. 1989 Apr;56(5):355-67. No abstract available. French.

  PMID: 2658001 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease

Interventions

Ceftriaxone; Injections, Intravenous

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Administration, Intravenous; Drug Administration Routes; Drug Therapy; Therapeutics; Injections

Study Officials

• Joshua Ho

  China Medical University, China

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2018
• First Posted: January 29, 2018
• Study Start: February 15, 2019
• Primary Completion: July 28, 2025
• Study Completion: December 31, 2025
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

TW (6)