Study on the Safety, Tolerance and Pharmacokinetics of Phenlarmide Tablets

NCT04693039 | Completed Phase 1 DMC

• 1 other identifier: FLZPD1003
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (27)

• 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

Study Arms (8)

FLZ-150mg

EXPERIMENTAL

Drug：Phenlarmide；Dosage：150mg；

Drug: Phenlarmide

FLZ-300mg

EXPERIMENTAL

Drug：Phenlarmide；Dosage：300mg；

Drug: Phenlarmide

FLZ-600mg

EXPERIMENTAL

Drug：Phenlarmide；Dosage：600mg；

Drug: Phenlarmide

FLZ-900mg

EXPERIMENTAL

Drug：Phenlarmide；Dosage：900mg；

Drug: Phenlarmide

Placebo-150mg

PLACEBO COMPARATOR

Drug：Placebo；Dosage：150mg；

Drug: Placebo

Placebo-300mg

PLACEBO COMPARATOR

Drug：Placebo；Dosage：300mg；

Drug: Placebo

Placebo-600mg

PLACEBO COMPARATOR

Drug：Placebo；Dosage：600mg；

Drug: Placebo

Placebo-900mg

PLACEBO COMPARATOR

Drug：Placebo；Dosage：900mg；

Drug: Placebo

Interventions

Phenlarmide DRUG

Dosage form：Tablet; Give the medicine once a day，4 weeks is a cycle of administration, a total of 3 cycles of administration.

Also known as: FLZ-150mg, FLZ-300mg, FLZ-600mg, FLZ-900mg

FLZ-150mg; FLZ-300mg; FLZ-600mg; FLZ-900mg

Placebo DRUG

Dosage form：Tablet; Give the medicine once a day，4 weeks is a cycle of administration, a total of 3 cycles of administration.

Also known as: Placebo-150mg, Placebo-300mg, Placebo-600mg, Placebo-900mg

Placebo-150mg; Placebo-300mg; Placebo-600mg; Placebo-900mg

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Understand and sign the informed consent, understand the research process and requirements, and volunteer to participate in the study;
• over 30 years old and have no gender limit;
• Patients diagnosed with Parkinson's disease according to the Chinese diagnostic criteria for Parkinson's disease (2016 Edition);
• Hoehn-Yahr grade ≤ 3;
• The Unified Parkinson's disease scale (UPDRS) motor score (Part III) ≥ 10;
• Not using anti Parkinson's disease drugs within 28 days before enrollment;
• 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;
• 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.

You may not qualify if:

• 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);
• 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;
• Those who have received neurosurgical operation or electrical stimulation (such as pallidotomy, thalamotomy, deep brain electrical stimulation, etc.);
• 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;
• Patients with clinically significant renal dysfunction: creatinine clearance rate (CCR) \< 30 ml / min (using Cockcroft-Gault formula);
• 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;
• There is a history of heart, liver, kidney, respiratory, digestive, endocrine, immune or blood system diseases considered by researchers to be serious;
• During the screening period, the patients with HIV positive, HBV or HCV infection and syphilis infection were active;
• 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;
• There were significant food or drug allergy history or hypersensitivity reaction judged by researchers as having clinical significance;
• Participants in any clinical trials within 3 months before administration of the study;
• 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;
• Those considered unsuitable by the researchers to participate in this clinical trial.

Sponsors & Collaborators

• Shijiazhuang Yiling Pharmaceutical Co. Ltd: lead
• Xuanwu Hospital, Beijing: collaborator

Study Sites (1)

Chen Biao

Beijing, Beijing Municipality, 100053, China

Location

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• biao chen

  Xuanwu Hospital, Beijing

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2020
• First Posted: January 5, 2021
• Study Start: February 23, 2021
• Primary Completion: October 29, 2021
• Study Completion: October 29, 2021
• Last Updated: January 3, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)