Study on the Safety, Tolerance and Pharmacokinetics of Phenlarmide Tablets

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

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.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Phenlarmide; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Chen Biao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FLZ-150mg; Drug：Phenlarmide；Dosage：150mg；	Drug: Phenlarmide; Dosage form：Tablet; Give the medicine once a day，4 weeks is a cycle of administration, a total of 3 cycles of administration.; Other Names: FLZ-150mg; FLZ-300mg; FLZ-600mg; FLZ-900mg
Experimental: FLZ-300mg; Drug：Phenlarmide；Dosage：300mg；	Drug: Phenlarmide; Dosage form：Tablet; Give the medicine once a day，4 weeks is a cycle of administration, a total of 3 cycles of administration.; Other Names: FLZ-150mg; FLZ-300mg; FLZ-600mg; FLZ-900mg
Experimental: FLZ-600mg; Drug：Phenlarmide；Dosage：600mg；	Drug: Phenlarmide; Dosage form：Tablet; Give the medicine once a day，4 weeks is a cycle of administration, a total of 3 cycles of administration.; Other Names: FLZ-150mg; FLZ-300mg; FLZ-600mg; FLZ-900mg
Experimental: FLZ-900mg; Drug：Phenlarmide；Dosage：900mg；	Drug: Phenlarmide; Dosage form：Tablet; Give the medicine once a day，4 weeks is a cycle of administration, a total of 3 cycles of administration.; Other Names: FLZ-150mg; FLZ-300mg; FLZ-600mg; FLZ-900mg
Placebo Comparator: Placebo-150mg; Drug：Placebo；Dosage：150mg；	Drug: Placebo; Dosage form：Tablet; Give the medicine once a day，4 weeks is a cycle of administration, a total of 3 cycles of administration.; Other Names: Placebo-150mg; Placebo-300mg; Placebo-600mg; Placebo-900mg
Placebo Comparator: Placebo-300mg; Drug：Placebo；Dosage：300mg；	Drug: Placebo; Dosage form：Tablet; Give the medicine once a day，4 weeks is a cycle of administration, a total of 3 cycles of administration.; Other Names: Placebo-150mg; Placebo-300mg; Placebo-600mg; Placebo-900mg
Placebo Comparator: Placebo-600mg; Drug：Placebo；Dosage：600mg；	Drug: Placebo; Dosage form：Tablet; Give the medicine once a day，4 weeks is a cycle of administration, a total of 3 cycles of administration.; Other Names: Placebo-150mg; Placebo-300mg; Placebo-600mg; Placebo-900mg
Placebo Comparator: Placebo-900mg; Drug：Placebo；Dosage：900mg；	Drug: Placebo; Dosage form：Tablet; Give the medicine once a day，4 weeks is a cycle of administration, a total of 3 cycles of administration.; Other Names: Placebo-150mg; Placebo-300mg; Placebo-600mg; Placebo-900mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the dose limiting toxicity (DLT)	The occurrence of Dose limiting toxicity.	through study completion, an average of 6 months
Tmax, ss	After administration, the time when the highest concentration of drug appeared in plasma	through study completion, an average of 6 months
Efficacy evaluation	explore the efficacy of fenolamide tablets in the treatment of early and middle stage Parkinson's disease, and observe the changes of UPDRS and CGI.	through study completion, an average of 6 months
maximum tolerable dose (MTD)	The occurrence of Maximum tolerable dose.	through study completion, an average of 6 months
adverse events	The occurrence rate of adverse events.	through study completion, an average of 6 months
adverse reactions	The occurrence rate of adverse reactions	through study completion, an average of 6 months
blood routine	Check whether the red blood cell system, white blood cell system and platelet system are normal	through study completion, an average of 6 months
blood biochemistry	The contents of various ions, sugars, lipids, proteins, enzymes, hormones and metabolites in blood were detected	through study completion, an average of 6 months
coagulation function	Four coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB) were evaluated.	through study completion, an average of 6 months
urine routine	Urine routine examination includes urine color, transparency, pH, red blood cells, white blood cells, epithelial cells, tube type, protein, specific gravity and urine sugar.	through study completion, an average of 6 months
stool routine	Routine stool tests include the detection of red and white blood cells in feces, bacterial sensitivity test, occult blood test (OB) and inspection of eggs.	through study completion, an average of 6 months
Body temperature	One of the vital signs.	through study completion, an average of 6 months
12 lead ECG	Evaluation of QT interval	through study completion, an average of 6 months
Blood pressure	Assess whether systolic blood pressure and diastolic blood pressure are normal.	through study completion, an average of 6 months
Heart rate	One of the vital signs.	through study completion, an average of 6 months
Breathing	Assess if breathing is normal	through study completion, an average of 6 months
Cmax, ss	The highest concentration of the drug in the plasma after administration	through study completion, an average of 6 months
Cavg, ss	The quotient of the area under the plasma concentration time curve divided by the interval time within a dose interval after the plasma concentration reaches the steady state.	through study completion, an average of 6 months
Ke	The ratio of the amount of compound eliminated from the body to the total amount in the body in unit time	through study completion, an average of 6 months
t1/2	The time required for the concentration of a drug to drop by half in an organism	through study completion, an average of 6 months
CL/F (fenoxamide prototype only)	The amount of a substance excreted by the kidney per minute	through study completion, an average of 6 months
Vz/F (fenoxamide prototype only)	After the drug reaches dynamic equilibrium in the body, the ratio of the drug dose in the body to the blood concentration is called the apparent distribution volume	through study completion, an average of 6 months
AUC0-24, ss	After administration, the area under the 0-24 hour time curve of blood concentration absorbed into human circulation	through study completion, an average of 6 months
AUCinf, ss	After administration, the area under the time curve of 0-infinity of the blood concentration absorbed into human circulation	through study completion, an average of 6 months
AUC0-last，ss	After administration, the area under the time curve of 0-the last accurately determined sample collection time of the blood concentration absorbed into human circulation	through study completion, an average of 6 months
AUC_%Extrap	the area under the curve that has been derived after extrapolation of Residual Area	through study completion, an average of 6 months
DF	The index reflecting the unbalanced situation of transportation in time	through study completion, an average of 6 months

Collaborators and Investigators

• Sponsor: Shijiazhuang Yiling Pharmaceutical Co. Ltd
• Collaborators: Xuanwu Hospital, Beijing
• Investigators: Principal Investigator: biao chen, Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2021
• Primary Completion (Actual): October 29, 2021
• Study Completion (Actual): October 29, 2021

Study Registration Dates

• First Submitted: December 28, 2020
• First Submitted That Met QC Criteria: December 31, 2020
• First Posted (Actual): January 5, 2021

Study Record Updates

• Last Update Posted (Actual): January 3, 2022
• Last Update Submitted That Met QC Criteria: December 11, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: FLZPD1003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No