Ning Shen Dan Xiang Gao Fang for Heart-Kidney Disharmony Insomnia

Use the PSQI scale to assess the subjects' sleep quality . The PSQI consists of 7 dimensions: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Each dimension is scored from 0 to 3 points, with higher scores indicating greater severity of sleep disturbance.

The total PSQI score ranges from 0 to 21. A PSQI score >7 indicates poor sleep quality, while a PSQI score ≤7 indicates good sleep quality.

Use the ISI scale to assess the severity of insomnia in the subjects. This scale consists of 7 questions, each scored from 0 to 4 points (5 grading levels in total). No clinically significant insomnia (i.e., cured): 0 ≤ ISI ≤ 7; mild insomnia: 8 ≤ ISI ≤ 14; moderate insomnia: 15 ≤ ISI ≤ 21; severe insomnia: 22 ≤ ISI ≤ 28.

Assessed via an Electronic Patient-Reported Outcome (ePRO) daily sleep diary. This measure reports the change in the patient's daily total sleep time.

Unit of Measure: Minutes ( or Hours)

SOL is defined as the time interval from the point the patient attempts to fall asleep until the onset of sleep. Data is recorded daily by patients via an electronic Patient-Reported Outcome (ePRO) sleep diary. Unit of Measure: Minutes

Assessed via an electronic Patient-Reported Outcome(ePRO) daily sleep diary. WASO refers to the total amount of time the patient spent awake after initially falling asleep and before fully waking up for the day.Unit of Measure: Minutes

Assessed via an Assessed via an electronic Patient-Reported Outcome(ePRO) daily sleep diary. This measure records the total frequency of nighttime awakenings experienced by the patient after initial sleep onset.

Unit of Measure: Count (or Number of awakenings)

The TCM symptom grading and quantification criteria include three main symptoms-difficulty falling asleep, vexation and insomnia, and excessive dreaming-which are scored on a 0, 2, 4, or 6 scale according to severity and frequency; the nine secondary symptoms-palpitations, tinnitus, soreness and weakness of the waist and knees, tidal fever with night sweats, vexing heat in the five centers, dry throat, dry mouth, seminal emission in men, and irregular menstruation in women-are scored on a 0-3 scale according to severity and frequency. Tongue and pulse: red tongue tip with scant coating and a thready rapid pulse.The Nimodipine method is used to assess the therapeutic efficacy of TCM syndromes. The syndrome score calculation formula is:

((pre-treatment score - post-treatment score)/pre-treatment score)*100% Effective: All symptoms and signs show improvement; syndrome score reduction ≥50%; Ineffective: Symptoms and signs show no obvious improvement; syndrome score reduction <50%.

Rebound insomnia is defined as Pittsburgh Sleep Quality Index (PSQI) total score > baseline score at 1 week following drug discontinuation

Record the occurrence of symptoms such as dry mouth, soreness in the mouth and tongue, swollen and painful gums, excessive hunger and appetite, and constipation.

Vital signs are monitored as a key safety parameter to evaluate the physiological tolerability and potential adverse effects of the investigational treatment.

Body temperature (°C) is measured under standardized conditions (rest ≥5 minutes, using calibrated equipment) by trained study personnel.

Vital signs are monitored as a key safety parameter to evaluate the physiological tolerability and potential adverse effects of the investigational treatment.

Pulse rate (beats per minute, bpm) is measured under standardized conditions (rest ≥5 minutes, using calibrated equipment) by trained study personnel.

Vital signs are monitored as a key safety parameter to evaluate the physiological tolerability and potential adverse effects of the investigational treatment.

Respiratory rate (breaths per minute) is measured under standardized conditions (rest ≥5 minutes, using calibrated equipment) by trained study personnel.

Vital signs are monitored as a key safety parameter to evaluate the physiological tolerability and potential adverse effects of the investigational treatment.

Blood pressure (systolic and diastolic, mmHg) is measured under standardized conditions (rest ≥5 minutes, using calibrated equipment) by trained study personnel. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) are recorded and reported separately.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory.

Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Hematology (Blood Routine): Red Blood Cell count (RBC) Unit: ×10¹²/L (Number of red blood cells per liter of blood × 10¹²) Normal range: Male (4.30-5.80) × 10¹²/L, Female (3.80-5.10) × 10¹²/L

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory.

Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Hematology (Blood Routine): White Blood Cell count (WBC) Unit: ×10⁹/L (Number of white blood cells per liter of blood × 10⁹) Normal range: 3.50 - 9.50 × 10⁹/L

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory.

Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Hematology (Blood Routine): Platelet count (PLT) Unit: ×10⁹/L (Number of platelets per liter of blood × 10⁹) Normal range: 125 - 350 × 10⁹/L

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory.

Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Hematology (Blood Routine): Hemoglobin (Hb)-Hemoglobin Concentration Unit: g/L (grams per liter) or g/dL Normal range: 130.0-175.0 g/L for males; 115.0-150.0 g/L for females

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Urinalysis (Urine Routine): Protein (PRO) Unit: Qualitative/Semi-quantitative, typically reported as: Negative (-), Trace (±), +, ++, +++, ++++ (or mg/dL, g/L) Normal is considered negative.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Urinalysis (Urine Routine): Glucose (GLU) Unit: Qualitative/Semi-quantitative, typically reported as: Negative (-), Trace (±), +, ++, +++, ++++ (or mmol/L, mg/dL) Normal is considered negative.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Urinalysis (Urine Routine): Erythrocytes (ERY) Unit: per high-power field (/HPF) or per microliter (μL) (microscope count) The normal range is 0 to 3 per HPF.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Urinalysis (Urine Routine): Leukocytes (LEU) Unit: per high-power field (/HPF) or per microliter (μL) (microscope count) The normal range is < 25.00/μL

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Liver Function: Alanine Aminotransferase (ALT) Unit: U/L (units per liter) The normal range is 9.0 - 50.0 U/L.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Liver Function: Aspartate Aminotransferase (AST) Unit: U/L (units per liter) The normal range is 15.0 - 40.0 U/L.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Liver Function: Total Bilirubin (TBIL) Unit: μmol/L (micromoles per liter) The normal range is 0 - 23.0 μmol/L.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Liver Function:Gamma-Glutamyl Transferase（γ-GT） Unit: U/L (units per liter) Normal range: 0 - 55.0 U/L for males; 0 - 38.0 U/L for females.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Liver Function:Alkaline Phosphatase (ALP) Unit: U/L (units per liter) The normal range is 45.0 - 125.0 U/L.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Renal Function: Serum Creatinine (Scr) Unit: μmol/L (micromoles per liter) or mg/dL Normal range: 57.0-111.0 μmol/L for males; 41.0-81.0 μmol/L for females.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Human Chorionic Gonadotropin (β-hCG) Unit: mIU/L (milli-international units per liter) The normal range for non-pregnant females is < 5.0 mIU/L. Values ≥ 5.0 mIU/L may indicate pregnancy or require further clinical evaluation.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Fasting Plasma Glucose (FPG) Unit: mmol/L (millimoles per liter) The normal range is 3.90 - 6.10 mmol/L.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Blood lipid：Total Cholesterol (TC) Unit: mmol/L (millimoles per liter) The normal range is 3.10 - 5.69 mmol/L.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Blood lipid：Triglycerides (TG) Unit: mmol/L (millimoles per liter) The normal range is 0.56 - 1.47 mmol/L.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Blood lipid：High-Density Lipoprotein Cholesterol (HDL-C) Unit: mmol/L (millimoles per liter) The normal range is 0.91 - 2.06 mmol/L for males and 1.09 - 2.28 mmol/L for females.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Blood lipid：Low-Density Lipoprotein Cholesterol (LDL-C) Unit: mmol/L (millimoles per liter) The normal range is < 3.10 mmol/L.

Heart rate (beats per minute) is measured from a electrocardiogram recorded after at least 5 minutes of rest in a supine position, using calibrated equipment. Measurements are performed by trained personnel and interpreted by qualified investigators or cardiologists. Used for cardiac safety monitoring. Clinically significant changes are reported as adverse events.

Unit of Measure: beats per minute (bpm)

PR interval (milliseconds) is measured from a electrocardiogram recorded after at least 5 minutes of rest in a supine position, using calibrated equipment. Measurements are performed by trained personnel and interpreted by qualified investigators or cardiologists. Assessed as part of cardiac conduction safety evaluation. Clinically significant prolongation is reported as an adverse event.

Unit of Measure: milliseconds (ms)

QRS duration (milliseconds) is measured from a electrocardiogram recorded after at least 5 minutes of rest in a supine position, using calibrated equipment. Measurements are performed by trained personnel and interpreted by qualified investigators or cardiologists. Monitored for potential ventricular conduction abnormalities. Clinically significant changes are reported as adverse events.

Unit of Measure: milliseconds (ms)

QT interval (milliseconds) is measured from a electrocardiogram recorded after at least 5 minutes of rest in a supine position, using calibrated equipment. Measurements are performed by trained personnel and interpreted by qualified investigators or cardiologists. Used for cardiac repolarization safety assessment.

Unit of Measure: milliseconds (ms)

Corrected QT interval (QTc, milliseconds) is calculated from the QT interval on a electrocardiogram (recorded after ≥5 minutes rest, supine position, calibrated equipment) using Bazett or Fridericia formula as specified in the protocol. Interpreted by qualified cardiologists or trained investigators. QTc prolongation (e.g., >500 ms) is considered clinically significant and reported as an adverse event. Key cardiac safety parameter.

Unit of Measure: milliseconds (ms)

Clinical assessment of skin color, turgor, rashes, lesions, and mucous membrane integrity. Results are categorized as: Normal, Abnormal Not Clinically Significant (NCS), or Abnormal Clinically Significant (CS).

Palpation and assessment of cervical, axillary, and inguinal lymph nodes for enlargement, consistency, or tenderness. Results are categorized as: Normal, Abnormal Not Clinically Significant (NCS), or Abnormal Clinically Significant (CS).

Evaluation of the skull, eyes, ears, nose, throat, and thyroid gland.Results are categorized as: Normal, Abnormal Not Clinically Significant (NCS), or Abnormal Clinically Significant (CS).

Evaluation of limbs, joints, edema, and peripheral pulses.Results are categorized as: Normal, Abnormal Not Clinically Significant (NCS), or Abnormal Clinically Significant (CS).

Physical examination of the thorax, including lung auscultation and cardiac assessment (heart sounds and rhythm). Results are categorized as: Normal, Abnormal Not Clinically Significant (NCS), or Abnormal Clinically Significant (CS).

Inspection, auscultation, percussion, and palpation of the abdomen, including liver and spleen assessment.Results are categorized as: Normal, Abnormal Not Clinically Significant (NCS), or Abnormal Clinically Significant (CS).

Assessment of cranial nerves, motor/sensory function, reflexes, and coordination.Results are categorized as: Normal, Abnormal Not Clinically Significant (NCS), or Abnormal Clinically Significant (CS).

Clinical assessment of any other body systems or general physical findings not captured in specific systemic exams (e.g., spine, gait, or general appearance). Results are categorized as: Normal, Abnormal Not Clinically Significant (NCS), or Abnormal Clinically Significant (CS).

Adverse events will be evaluated in terms of type, incidence, severity, time of onset, and relationship to the study drug.

Types of adverse events are classified as: Adverse Event (AE), Serious Adverse Event (SAE), and Suspected Unexpected Serious Adverse Reaction (SUSAR).

Severity is graded as: mild, moderate, or severe. Mild: The subject can tolerate the event; it does not interfere with ongoing treatment, requires no special intervention, and has no impact on the subject's recovery.

Moderate: The subject finds the event difficult to tolerate; it necessitates discontinuation of the study drug or special treatment, and it directly affects the subject's recovery.

Severe: The event is life-threatening, results in death or permanent disability/incapacity, and requires immediate discontinuation of the study drug or emergency intervention.

Plasma concentration measured from blood samples collected opportunistically at Week 4 (or Week 8/early discontinuation). Cmax is the maximum observed concentration post-dose. Parameters estimated using non-compartmental analysis or population PK modeling due to sparse sampling. Geometric mean and variability reported. Assessed as an exploratory pharmacokinetic biomarker.

Unit of Measure: ng/mL (or appropriate unit, e.g., nmol/L)

Area under the concentration-time curve from time zero to the last measurable concentration (AUC0-last) , estimated from sparse opportunistic sampling at Week 4 (or Week 8) using population PK methods. Geometric mean reported. Exploratory PK biomarker of exposure.

Unit of Measure: h·ng/mL (or appropriate, e.g., h·nmol/L）

Evaluation of microbial richness and evenness within fecal samples using 16S rRNA sequencing. Alpha-diversity represents the biological variety within a single sample.

Unit of Measure: Shannon Diversity Index (a calculated score typically ranging from 0 to 5, where higher values indicate greater diversity).

Assessment of the taxonomic composition of the gut microbiota at the genus and species levels via metagenomic sequencing.

Unit of Measure: Percentage of total sequences (%).

Quantitative analysis of major SCFAs (acetate, propionate, and butyrate) using GC-MS. The sum of these concentrations will be reported.

Unit of Measure: μ mol/g of feces.

Untargeted metabolomics analysis using LC-MS/GC-MS to identify global metabolic shifts and differential metabolites induced by the treatment.

Unit of Measure: Normalized peak intensity (arbitrary units).