Clinical trial NCT04693039: Study on the Safety, Tolerance and Pharmacokinetics of Phenlarmide Tablets
Official title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerance and Pharmacokinetics of Phenlarmide Tablets in Patients With Parkinson's Disease in the Early and Middle Stages
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson Disease
Lead sponsor: Shijiazhuang Yiling Pharmaceutical Co. Ltd
Sponsor class: INDUSTRY
Collaborators: name: Xuanwu Hospital, Beijing
First posted: 2021-01-05
Enrollment: 40
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 1. To evaluate the safety and tolerability of Phenlarmide tablets in patients with Parkinson's disease in the early and middle stages.
2. To evaluate the pharmacokinetics of Phenlarmide tablets in patients with Parkinson's disease.
3. To explore the efficacy of Phenlarmide tablets in the treatment of early and mid-term Parkinson's disease.

Detailed description: 1. Objective to evaluate the tolerance and safety of multiple administration of fenloramide tablets in patients with early and mid-term Parkinson's disease: To evaluate the adverse events of DLT and MTD, adverse reactions, clinical laboratory tests (blood routine, blood biochemistry, coagulation function, urine routine, stool routine), vital signs, 12 lead ECG and physical examination of fenloramide tablets in patients with early and mid-term Parkinson's disease .
2. Objective to evaluate the pharmacokinetics of fenloramide tablets in patients with Parkinson's disease in early and middle stages. The main PK parameters included Tmax, SS, Cmax, SS, cavg, SS, Ke, T1 / 2, Cl / F (only fenloramide prototype), VZ / F (only fenloramide prototype), auc0-24, SS, aucinf, SS, auc0 last, SS, AUC_ %Extrap, DF, etc.
3. Objective to explore the efficacy of fenloramide tablets in the treatment of early and mid-term Parkinson's disease, and to observe the changes of UPDRS and CGI.

Eligibility criteria: Inclusion Criteria:

1. Understand and sign the informed consent, understand the research process and requirements, and volunteer to participate in the study;
2. over 30 years old and have no gender limit;
3. Patients diagnosed with Parkinson's disease according to the Chinese diagnostic criteria for Parkinson's disease (2016 Edition);
4. Hoehn-Yahr grade ≤ 3;
5. The Unified Parkinson's disease scale (UPDRS) motor score (Part III) ≥ 10;
6. Not using anti Parkinson's disease drugs within 28 days before enrollment;
7. If the subjects are receiving dopamine receptor agonists (such as Pramipexole, etc.), anticholinergic drugs (such as Benzhexol Hydrochloride, etc.), monoamine oxidase B (MAO-B) inhibitors (such as Selegiline, Rasagiline, etc.), and N-methyl-D-aspartate (NMDA) receptor antagonists (such as Amantadine), they should stop using the drugs 28 days before the screening period;
8. Patients who had been treated with levodopa preparation (including levodopa compound preparation) for less than 6 months before screening, and had not received levodopa preparation treatment within 28 days before screening period.

Exclusion Criteria:

1. Atypical Parkinson's symptoms due to the use of drugs (such as Flunarizine, Metoclopramide), nervous system diseases, genetic metabolic diseases, encephalitis, cerebrovascular diseases or other degenerative diseases (such as progressive supranuclear paralysis);
2. Patients with dementia, active mental illness or hallucination, severe depression (Beck Depression Scale - Ⅱ ≥ 29 points at screening), or Mini-Mental State Examination (MMSE) \< 25 points;
3. Those who have received neurosurgical operation or electrical stimulation (such as pallidotomy, thalamotomy, deep brain electrical stimulation, etc.);
4. Patients with clinically significant abnormal liver function were defined as total bilirubin \> 1.5 times of the upper limit of normal value or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2 times of the upper limit of normal value;
5. Patients with clinically significant renal dysfunction: creatinine clearance rate (CCR) \< 30 ml / min (using Cockcroft-Gault formula);
6. Patients with uncontrollable or severe cardiovascular diseases, including NYHA grade II or above congestive heart failure, unstable angina pectoris, myocardial infarction, arrhythmia requiring treatment at the time of screening, and QTc interval prolongation more than 480ms, in 6 months before the first administration of trial drug;
7. There is a history of heart, liver, kidney, respiratory, digestive, endocrine, immune or blood system diseases considered by researchers to be serious;
8. During the screening period, the patients with HIV positive, HBV or HCV infection and syphilis infection were active;
9. Patients with malignant tumor within 5 years before screening were excluded from cervical carcinoma in situ, skin basal cell or squamous cell carcinoma, local prostate cancer after radical operation and breast intraductal carcinoma in situ after radical operation;
10. There were significant food or drug allergy history or hypersensitivity reaction judged by researchers as having clinical significance;
11. Participants in any clinical trials within 3 months before administration of the study;
12. Pregnant or lactating women, or those whose serum hCG test is positive before trial administration, who are unable or unwilling to take contraceptive measures approved by the researcher during the study period and within 3 months after the end of the study according to the instructions of the researcher;
13. Those considered unsuitable by the researchers to participate in this clinical trial.

Primary outcomes:
measure: the dose limiting toxicity (DLT)
timeFrame: through study completion, an average of 6 months
measure: Tmax, ss
timeFrame: through study completion, an average of 6 months
measure: Efficacy evaluation
timeFrame: through study completion, an average of 6 months
measure: maximum tolerable dose (MTD)
timeFrame: through study completion, an average of 6 months
measure: adverse events
timeFrame: through study completion, an average of 6 months
measure: adverse reactions
timeFrame: through study completion, an average of 6 months
measure: blood routine
timeFrame: through study completion, an average of 6 months
measure: blood biochemistry
timeFrame: through study completion, an average of 6 months
measure: coagulation function
timeFrame: through study completion, an average of 6 months
measure: urine routine
timeFrame: through study completion, an average of 6 months
measure: stool routine
timeFrame: through study completion, an average of 6 months
measure: Body temperature
timeFrame: through study completion, an average of 6 months
measure: 12 lead ECG
timeFrame: through study completion, an average of 6 months
measure: Blood pressure
timeFrame: through study completion, an average of 6 months
measure: Heart rate
timeFrame: through study completion, an average of 6 months
measure: Breathing
timeFrame: through study completion, an average of 6 months
measure: Cmax, ss
timeFrame: through study completion, an average of 6 months
measure: Cavg, ss
timeFrame: through study completion, an average of 6 months
measure: Ke
timeFrame: through study completion, an average of 6 months
measure: t1/2
timeFrame: through study completion, an average of 6 months
measure: CL/F (fenoxamide prototype only)
timeFrame: through study completion, an average of 6 months
measure: Vz/F (fenoxamide prototype only)
timeFrame: through study completion, an average of 6 months
measure: AUC0-24, ss
timeFrame: through study completion, an average of 6 months
measure: AUCinf, ss
timeFrame: through study completion, an average of 6 months
measure: AUC0-last，ss
timeFrame: through study completion, an average of 6 months
measure: AUC_%Extrap
timeFrame: through study completion, an average of 6 months
measure: DF
timeFrame: through study completion, an average of 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chen Biao
state: Beijing
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: biao chen
role: PRINCIPAL_INVESTIGATOR
References: