Clinical Trials List
Protocol NumberBRICEFA20170414
NCT Number(ClinicalTrials.gov Identfier)NCT03413384
Active
2018-02-01 - 2024-12-31
Phase II
Recruiting5
Terminated5
ICD-10G20
Parkinson's disease
ICD-9332.0
Paralysis agitans
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
-
Trial Applicant
-
Sponsor
BrainX Corporation
-
Trial scale
Taiwan Multiple Center
-
Update
2026/02/01
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Ming-Che Kuo Division of Neurology
- YA-FANG CHEN Division of Radiology
- 范恬心 Division of Neurology
- CHUN-HWEI TAI Division of Neurology
- RUOH-FANG YEN Division of Nuclear Medicine
- 林洳甄 Division of Neurology
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Ming-Kuei Lu Division of Neurology
- Yu-Wan Yang Division of Neurology
- Hui-Chun Huang Division of Neurology
- Yu Ao
- Sheng-Ta Tsai
- 陳威良
- 謝德鈞 Division of Nuclear Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chun-Yu Chen
- Yo-Tsen Liu Division of Neurology
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- LI-MIN LIOU Division of Neurology
- 蔣宜璋醫師 Division of Radiology
- PING SONG CHOU Division of Neurology
- 張揚沛 Division of Neurology
- 林家揚醫師 Division of Nuclear Medicine
- MEI-CHUAN CHOU Division of Neurology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 王心怡醫師 Division of Nuclear Medicine
- 陳虹潔醫師 Division of Radiology
- WEI-JU LEE Division of Neurology
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Parkinson′s disease dementia
Objectives
Primary Study Objective
To evaluate the improvement of cognitive function in PDD patients with ceftriaxone
administration
Secondary Study Objectives
To evaluate the efficacy and safety profiles in PDD patients with ceftriaxone
administration
Exploratory Study Objectives
To evaluate the correlation of biomarkers with ceftriaxone treatment in PDD patients
Test Drug
ceftriaxone
Active Ingredient
Ceftriaxone sodium
Dosage Form
injection
Dosage
1
Endpoints
Primary Endpoint
Compare the treatment difference in mean net change in ADAS-Cog score with time
course
Secondary Endpoints
Efficacy
1. Changes in UPDRS score from baseline at week 17 and 33 visits
2. Changes in Judgment of Line Orientation Test score from baseline at week 17 and 33
visits
3. Changes in MMSE score from baseline at week 17 and 33 visits
4. Changes in CDR Scale score from baseline at week 17 and 33 visits
5. Changes in Color Trail Test score from baseline at week 17 and 33 visits
6. Changes in Tc-99m TRODAT SPECT image from baseline at week 17 and 33 visits
7. Change in MRI image from baseline, focus on atrophy rate of brain and dopaminergic
projection from substantia nigra to striatum at week 17 and 33 visits
Safety
1. Laboratory data changes:
Biochemistry
Total bilirubin, albumin, ALP, SGOT, SGPT, BUN, serum creatinine, γ-GT.
Hematology
Complete blood count: RBC count, WBC with differential counts, hemoglobin,
hematocrit, and platelet count.
Urinalysis
pH, color, appearance, gravity, erythrocyte, leukocyte, glucose, protein, ketones and
nitrite.
2. Changes in physical examinations
3. Changes in vital signs
4. Adverse events (AE) incidences over the study period
Exploratory Endpoints
1. Changes in biomarker α-synuclein data from baseline at week 17 and 33 visits
2. Changes in biomarker Aβ42 data from baseline at week 17 and 33 visits
Compare the treatment difference in mean net change in ADAS-Cog score with time
course
Secondary Endpoints
Efficacy
1. Changes in UPDRS score from baseline at week 17 and 33 visits
2. Changes in Judgment of Line Orientation Test score from baseline at week 17 and 33
visits
3. Changes in MMSE score from baseline at week 17 and 33 visits
4. Changes in CDR Scale score from baseline at week 17 and 33 visits
5. Changes in Color Trail Test score from baseline at week 17 and 33 visits
6. Changes in Tc-99m TRODAT SPECT image from baseline at week 17 and 33 visits
7. Change in MRI image from baseline, focus on atrophy rate of brain and dopaminergic
projection from substantia nigra to striatum at week 17 and 33 visits
Safety
1. Laboratory data changes:
Biochemistry
Total bilirubin, albumin, ALP, SGOT, SGPT, BUN, serum creatinine, γ-GT.
Hematology
Complete blood count: RBC count, WBC with differential counts, hemoglobin,
hematocrit, and platelet count.
Urinalysis
pH, color, appearance, gravity, erythrocyte, leukocyte, glucose, protein, ketones and
nitrite.
2. Changes in physical examinations
3. Changes in vital signs
4. Adverse events (AE) incidences over the study period
Exploratory Endpoints
1. Changes in biomarker α-synuclein data from baseline at week 17 and 33 visits
2. Changes in biomarker Aβ42 data from baseline at week 17 and 33 visits
Inclution Criteria
Inclusion Criteria
1. Patients are male or female, age 50-80 years, inclusive.
2. Diagnosis of idiopathic PD within less than 10 years duration based on the UK
Parkinson’s Disease Society Brain Bank Criteria and with a modified Hoehn and
Yahr Stage of I to III.
3. Patients have been receiving stable dose of medications equivalent up to 800 mg/day
of levodopa for Parkinson’s disease (See Section 13.8 for the list) 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 MDS Task Force criteria as the following items:
a. A diagnosis of PD based on UK Parkinson’s Disease Society Brain Bank Criteria
b. PD development prior to the onset of dementia based on patient/caregiver history
or records
c. Cognitive deficiency severe enough to impair daily life based on patient/caregiver
interview or pill questionnaire
d. Impairment of at least 2 of the following domains: attention, executive function,
visuo-constructive ability, memory
Besides, patients’ MMSE should be in the range of 18-25 (inclusive) or CDR scale in
the range of 0.5-2 and are currently not taking any treatment for dementia.
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.
a. 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).
b. 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.
c. 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
d. 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.
1. Patients are male or female, age 50-80 years, inclusive.
2. Diagnosis of idiopathic PD within less than 10 years duration based on the UK
Parkinson’s Disease Society Brain Bank Criteria and with a modified Hoehn and
Yahr Stage of I to III.
3. Patients have been receiving stable dose of medications equivalent up to 800 mg/day
of levodopa for Parkinson’s disease (See Section 13.8 for the list) 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 MDS Task Force criteria as the following items:
a. A diagnosis of PD based on UK Parkinson’s Disease Society Brain Bank Criteria
b. PD development prior to the onset of dementia based on patient/caregiver history
or records
c. Cognitive deficiency severe enough to impair daily life based on patient/caregiver
interview or pill questionnaire
d. Impairment of at least 2 of the following domains: attention, executive function,
visuo-constructive ability, memory
Besides, patients’ MMSE should be in the range of 18-25 (inclusive) or CDR scale in
the range of 0.5-2 and are currently not taking any treatment for dementia.
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.
a. 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).
b. 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.
c. 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
d. 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
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.
6. The patients have received neurosurgical intervention related to PD (e.g. 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 a history of hepatobiliary and /or pancreatic disease or abdominal
ultrasound examination imaging shows biliary system disease 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 should be
excluded :
a. Anticholinergic medication or amantadine currently or within 4 weeks prior to the
screening visit.
b. Cocaine, opioids, ethanol (binge drinking or heavy alcohol defined by SAMHSA
and NIAAA) currently or within 4 weeks prior to the screening visit; nicotine dependence, amphetamines, cannabinoids abuse history or taking currently or
within 3 months prior to the screening visit.
c. Acetylcholinesterase inhibitors or memantine currently or within 4 weeks prior to
the screening visit.
d. Ceftriaxone or cephalosporin or penicillin or β-lactam currently or within 4 weeks
prior to the screening visit.
e. Neuroleptic for treatment of psychotic symptoms (e.g., hallucinations) related to
their anti-Parkinson medication within 4 weeks prior to the screening visit.
f. Antipsychotics currently or within 4 weeks prior to the screening visit.
g. A drug that has severe hepatotoxic or renal toxic within 4 weeks prior to the
screening visit.
h. Warfarin, cyclosporin, vancomycin, amsacrine, aminoglycosides, fluconazole,
chloramphenicol currently or within 4 weeks prior to the screening visit.
13. Currently participating in another clinical trial or who participated in a previous
clinical trial and received any investigational product treatment within 4 weeks prior
to the screening visit.
14. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or
family members who suffer from such.
15. Patients who are not able to take MRI and TRODAT SPECT examination.
16. Patients who are pregnant or breast feeding.
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.
6. The patients have received neurosurgical intervention related to PD (e.g. 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 a history of hepatobiliary and /or pancreatic disease or abdominal
ultrasound examination imaging shows biliary system disease 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 should be
excluded :
a. Anticholinergic medication or amantadine currently or within 4 weeks prior to the
screening visit.
b. Cocaine, opioids, ethanol (binge drinking or heavy alcohol defined by SAMHSA
and NIAAA) currently or within 4 weeks prior to the screening visit; nicotine dependence, amphetamines, cannabinoids abuse history or taking currently or
within 3 months prior to the screening visit.
c. Acetylcholinesterase inhibitors or memantine currently or within 4 weeks prior to
the screening visit.
d. Ceftriaxone or cephalosporin or penicillin or β-lactam currently or within 4 weeks
prior to the screening visit.
e. Neuroleptic for treatment of psychotic symptoms (e.g., hallucinations) related to
their anti-Parkinson medication within 4 weeks prior to the screening visit.
f. Antipsychotics currently or within 4 weeks prior to the screening visit.
g. A drug that has severe hepatotoxic or renal toxic within 4 weeks prior to the
screening visit.
h. Warfarin, cyclosporin, vancomycin, amsacrine, aminoglycosides, fluconazole,
chloramphenicol currently or within 4 weeks prior to the screening visit.
13. Currently participating in another clinical trial or who participated in a previous
clinical trial and received any investigational product treatment within 4 weeks prior
to the screening visit.
14. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or
family members who suffer from such.
15. Patients who are not able to take MRI and TRODAT SPECT examination.
16. Patients who are pregnant or breast feeding.
The Estimated Number of Participants
-
Taiwan
106 participants
-
Global
106 participants
