A Randomized, Multi-center, Double-blind, Parallel-group, Placebo-controlled Phase II Study To Evaluate the Safety, Tolerance, Pharmacokinetics/Pharmacodynamics and Efficacy of SYHA1402 Tablets For the Treatment of Patients With Diabetic Peripheral Neuropathy in China
Overview
- Phase
- Phase 2
- Intervention
- SYHA1402 tablets
- Conditions
- Distal Symmetric Polyneuropathy (DSPN)
- Sponsor
- CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
- Enrollment
- 135
- Primary Endpoint
- Change from baseline in modified Toronto Clinical Neuropathy Score (mTCNS)- Sensory Test Score at week 16
- Last Updated
- 4 years ago
Overview
Brief Summary
This study aims to evaluate the safety, tolerance, pharmacokinetics/pharmacodynamics and efficacy of SYHA1402 tablets for the treatment of patients with diabetic peripheral neuropathy (DPN) in China.
Detailed Description
This is a randomized, multi-center, double-blind, parallel-group, placebo-controlled, phase II clinical trial to evaluate safety, tolerance, pharmacokinetics/pharmacodynamics and efficacy of SYHA1402 tablets in DPN patients. A total number of 135 patients will be randomized (2:2:1) into three groups. Patients between 18 and 75 years old and diagnosed with a Distal Symmetric Polyneuropathy (DSPN) prior to study enrolment will be enrolled. The study consists of 4 stages: a 2-week screening period, a 1-week placebo introduction period, a 16-week randomized double-blind treatment period, and a 2-week post-study follow-up period. The overall planned duration of this study is approximately 21 weeks.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent obtained before any trial-related activities voluntarily, understanding the procedures and methods of this study, and be willing to strictly follow the trial protocol;
- •Males or females, aged 18-75 years (both inclusive);
- •Diagnosed with type 1 or type 2 diabetes for more than 6 months, hemoglobin Alc (HbA1c) between 7% and 10% at screening, fasting plasma glucose (FPG) \<11.1 mmol/L, and the glucose-lowering treatment has been stable for at least 30 days and is expected to remain unchanged throughout the study;
- •According to the 《China Type 2 Diabetes Prevention and Cure Guidelines (2020 edition)》, those diagnosed with diabetic peripheral neuropathy are classified as distal symmetric polyneuropathy (DSPN), the diagnostic criteria consists of:(1) A clear history of diabetes; (2) Neuropathy appeared during or after diagnosis of diabetes; (3) Symptoms and signs are consistent with the performance of DPN; (4) Patients with clinical symptoms (pain, numbness, abnormal sensation, etc.), with abnormality in any 1 of 5 examinations (ankle reflexes, needle pain, vibration, pressure, temperature); Patients without symptoms, with abnormalities in any 2 of 5 examinations and a clinical diagnosis of DPN; (5) Excluding patients with neuropathy caused by other causes;
- •Toronto Clinical Neuropathy Score (TCNS) ≥ 6 points, with sensory test score ≥ 2 points at screening and baseline.
Exclusion Criteria
- •Those who meet any of the exclusion criteria will not be enrolled:
- •Patients with peripheral neuropathy caused by other diseases: such as cervical and lumbar vertebral disease, cerebrovascular disease, intracranial tumor or trauma, toxic peripheral neuropathy (e.g. chemotherapy, alcohol), Guillain-Barr é syndrome, multiple sclerosis, bone joints or tendon lesions, severe arteriovenous and vascular lesions, severe liver and kidney insufficiency, hyperthyroidism or degeneration, subclinical thyroid dysfunction, vitamin B12 deficiency, infection (e.g. human immunodeficiency virus), etc;
- •Patients with previous peripheral arterial disease, and significant intermittent claudication symptoms or previous lower extremity vascular bypass or angioplasty at screening;
- •History of malignant neoplasms (except cured basal cell skin cancer, in-situ carcinomas and papillary thyroid cancer) or history of antineoplastic therapy within 5 years prior to screening;
- •Patients with a change of more than 2 points in the same item of the mTCNS at screening and baseline;
- •Visual Analogue Scale (VAS) \> 8 points at screening;
- •Diabetic foot, diabetic peripheral vascular lesions, lower limb amputation, diabetic muscular atrophy, Charcot joint disease within 3 months prior to screening;
- •Acute complications such as severe hypoglycemia with loss of consciousness, diabetic ketoacidosis, diabetic hyperosmolar hyperglycemia syndrome, lactic acidosis, etc. within 3 months prior to screening;
- •Those who have used a prohibited combination drug within 3 months before screening must discontinue the drug for at least 1 month or 5 half-lives (whichever is longer) prior to screening visit, and the drug must be discontinued throughout the study period;
- •Any of the following cardiovascular events within 6 months prior to screening: unstable angina requiring hospitalization, myocardial infarction, coronary artery bypass transplantation, transdermal coronary intervention (diagnostic angiography is permitted), moderate to severe congestive heart failure (NYHA III or IV), atrial or ventricular arrhythmia (e.g. atrial fibrillation, ventricular tachycardia, etc.) requiring hospitalization, pacemaker or defibrillator implantation, temporary cerebral ischemic attacks or cerebrovascular accidents (e.g. strokes); Or coronary artery bypass grafting or revascularization is planned during the study;
Arms & Interventions
SYHA1402 1000 mg plus placebo 500 mg
Eligible patients will be randomly assigned to receive SYHA1402 1000 mg and placebo 500 mg twice daily for 16 weeks of treatment after a placebo introduction period.
Intervention: SYHA1402 tablets
SYHA1402 1000 mg plus placebo 500 mg
Eligible patients will be randomly assigned to receive SYHA1402 1000 mg and placebo 500 mg twice daily for 16 weeks of treatment after a placebo introduction period.
Intervention: Placebo
SYHA1402 1500 mg
Eligible patients will be randomly assigned to receive SYHA1402 1500 mg twice daily for 16 weeks of treatment after a placebo introduction period.
Intervention: SYHA1402 tablets
Placebo 1500 mg
Eligible patients will be randomly assigned to receive placebo 1500 mg twice daily for 16 weeks of treatment after a placebo introduction period.
Intervention: Placebo
Outcomes
Primary Outcomes
Change from baseline in modified Toronto Clinical Neuropathy Score (mTCNS)- Sensory Test Score at week 16
Time Frame: From baseline to week 16 post-dose
To Compare SYHA1402 with placebo, the overall score and symptom score of mTCNS changes from baseline at week 16. The mTCNS examines signs and symptoms of polyneuropathy. It consists of a questionnaire which explores the presence of foot pain, numbness, tingling, weakness, and loss of sensation leading to ataxia. Secondly, sensory tests will be performed including sensation for pinprick, light touch, temperature, vibration and position sense. The minimum value is 0 meaning the patient does not show any signs or symptoms of polyneuropathy and the maximum value is 33 meaning the patient presents with severe signs and symptoms of polyneuropathy.
Secondary Outcomes
- Change from baseline in Toronto Clinical Neuropathy Score (TCNS) at week 16(From baseline to week 16 post-dose)
- Clearance (CL)(Pre-dose and multiple timepoints up to 16 weeks)
- Pharmacodynamics (PD) indicator(Pre-dose and multiple timepoints up to 16 weeks)
- Incidence of adverse events (AEs)(Throughout the study period, an average of 21 weeks)
- Change from baseline in overall score and symptom score of mTCNS at week 16(From baseline to week 16 post-dose)
- Change from baseline in Visual Analogue Scale (VAS) at week 16(From baseline to week 16 post-dose)
- Volume of Distribution (V)(Pre-dose and multiple timepoints up to 16 weeks)
- Change from baseline in Nerve Conduction Velocities (NCVs) and Amplitude at week 16(From baseline to week 16 post-dose)
- Change from baseline in the 36-Item Shot-Form Health Survey (SF-36) score at week 16(From baseline to week 16 post-dose)