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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
135
SYHA1402 tablets, oral, twice daily
Placebo, oral, twice daily
Change from baseline in modified Toronto Clinical Neuropathy Score (mTCNS)- Sensory Test Score at week 16
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.
Time frame: From baseline to week 16 post-dose
Change from baseline in overall score and symptom score of mTCNS at week 16
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.
Time frame: From baseline to week 16 post-dose
Change from baseline in Toronto Clinical Neuropathy Score (TCNS) at week 16
To Compare SYHA1402 with placebo, the Toronto Clinical Neuropathy Score (TCNS) changes from baseline at week 16. Scales are defined as follows: 0-5 = no neuropathy; 6-8 = mild neuropathy; 9-11 = moderate neuropathy; ≥ 12 = severe neuropathy.
Time frame: From baseline to week 16 post-dose
Change from baseline in Nerve Conduction Velocities (NCVs) and Amplitude at week 16
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To Compare SYHA1402 with placebo, the Nerve Conduction Velocities (NCVs) and Amplitude changes from baseline at week 16.
Time frame: From baseline to week 16 post-dose
Change from baseline in Visual Analogue Scale (VAS) at week 16
To Compare SYHA1402 with placebo, the Visual Analogue Scale (VAS) changes from baseline at week 16. Including local pain, limb numbness, paresthesia (e.g. burning sensation, formication, electrical sensation). Participants rated their pain on a 100 millimeter (mm) Visual Analog Scale (VAS) ranging from 0 mm = no pain to 100 mm = worst possible pain.
Time frame: From baseline to week 16 post-dose
Change from baseline in the 36-Item Shot-Form Health Survey (SF-36) score at week 16
To Compare SYHA1402 with placebo, the 36-Item Shot-Form Health Survey (SF-36) score changes from baseline at week 16. The SF-36 quality of life scale is used to monitor change in subject reported functionality, well-being, and overall health status. The score of each part ranges from 0 (worst score) to 100 (best score).
Time frame: From baseline to week 16 post-dose
Clearance (CL)
Rate and Extent of Absorption SYHA1402 by Assessment of the Apparent Clearance
Time frame: Pre-dose and multiple timepoints up to 16 weeks
Volume of Distribution (V)
Rate and Extent of Absorption SYHA1402 by Assessment of the Apparent Volume of Distribution
Time frame: Pre-dose and multiple timepoints up to 16 weeks
Pharmacodynamics (PD) indicator
Proportional change from baseline in whole blood/red blood cell sorbitol concentration (%)
Time frame: Pre-dose and multiple timepoints up to 16 weeks
Incidence of adverse events (AEs)
Incidence of adverse events (AEs)
Time frame: Throughout the study period, an average of 21 weeks