Comparative Open-label,Randomized, Fasting/Fed, Single Dose, Three-way Crossover Bioequivalence Study of Valsartan and Amlodipine Tablets (Hua Yuan Pharmaceutical LLC, China) and Valsartan and Amlodipine Tablets (Ⅰ) (Novartis Pharma Schweiz AG, Switzerland)
Phase: PHASE1
Conditions: Healthy
Sponsor: Second Affiliated Hospital of Wenzhou Medical University

A Bioequivalence Study of Valsartan / Amlodipine From Valsartan and 
Amlodipine Tablets (Hua yuan Pharmaceutical LLC, China) and 
Valsartan and Amlodipine Tablets (Ⅰ) (Novartis Pharma Schweiz 
AG, Switzerland) 
 
Study Details 
Study Description：                                             
Brief Summary: 
Comparative randomized, single dose, three periods, three-way crossover open-label study to 
determine the bioequivalence of Valsartan and Amlodipine Tablets (Hua yuan 
Pharmaceutical LLC, China) and Valsartan and Amlodipine Tablets (Ⅰ) (Novartis Pharma 
Schweiz AG, Switzerland). 
 
Condition or disease Intervention/treatment 
Phase 
healthy 
Drug: Valsartan and Amlodipine Tablets 
Drug: Valsartan and Amlodipine Tablets 
The bioequivalence 
study 
Detailed Description: 
Primary Pharmacokinetic Parameters: Cmax, Area under cover (AUC0→t and 
AUC0→∞ ) .Secondary Pharmacokinetic Parameters:  tmax and t1/2. The method of judging 
bioequivalence of three-cross-section repeating experiment design: first of all, the 
calculation of the SWR of the AUC and Cmax, if SWR≥0.294, the use of  RSABE analysis; if 
Swr<0.294, the average Bioequivalence analysis method with Non-scale (bioequivalence 
limit is 80%~125 %）. 
A comprehensive final report will be issued upon the completion of the study. 
 
 
Study Design:                                                   
Study Type : Interventional  (Clinical Trial) 
Actual Enrollment : 84 participants 
Allocation: Randomized 
Intervention Model: Crossover Assignment 
Masking: 
None (Open Label) 
Official Title: 
Comparative Open-label,Randomized, Fasting/Fed, Single Dose, Three-way 
Crossover Bioequivalence Study of  Valsartan and Amlodipine Tablets (Hua yuan 
Pharmaceutical LLC, China) and Valsartan and Amlodipine Tablets (Ⅰ) (Novartis Pharma 
Schweiz AG, Switzerland) 
Study Start Date : 
 
Actual Primary Completion Date :  
Actual Study Completion Date : 
 
 
 

 
 
Arms and Interventions:                                       
Arm 
Intervention/treatment 
Experimental: T Test  
Test drug(Valsartan / Amlodipine)1 tablet 
contains Valsartan 80mg& Amlodipine 
5mg 
Drug: Valsartan and Amlodipine Tablets 
1 tablet contains Valsartan 80mg& 
Amlodipine 5mg 
Active Comparator: R Reference 
Reference drug(Valsartan / Amlodipine)1 
tablet contains Valsartan 80mg& 
Amlodipine 5mg 
Drug: Valsartan and Amlodipine Tablets 
(Ⅰ) 
1 tablet contains Valsartan 80mg& 
Amlodipine 5mg 
 
 
Outcome Measures:                                                
Primary Outcome Measures: 
Bioequivalence based on Cmax [ Time Frame: Up to 96 hours post dose in each treatment 
period] 
Bioequivalence based on AUC parameters [ Time Frame: Up to 96 hours post dose in each 
treatment period] 
 
Secondary Outcome Measures: 
Number of subjects with adverse events (AE)s [ Time Frame: Up to 96 hours post dose in 
each treatment period] 
Safety and tolerability parameters will include recording of AEs 
 
Safety assessed by vital sign measurement [ Time Frame: Up to 96 hours post dose in each 
treatment period] 
Vital sign measurement will include blood pressure, pulse rate, respiration rate and ear 
temperature 
Measure of clinical laboratory test values to access safety [ Time Frame: Up to 96 hours post 
dose in each treatment period] 
Clinical laboratory tests will include blood biochemistry, CBC, urine routine examination and 
ECG. 
 
Eligibility Criteria:                                                  
Ages Eligible for Study:  
18 Years to 45 
Years   (Adult) 
Sexes Eligible for Study:  
All 
Accepts Healthy Volunteers:  
Yes 
Criteria 
Inclusion Criteria: 
1.Healthy male or non-pregnant non-lactating female, age 18 to 45 years, including the 
critical value. 

2. Male weight ≥ 50kg, female weight ≥ 45kg, body mass index (BMI) between 19 and 
28kg / m2, including the critical value. 
3. Good health, no heart, liver, kidney, digestive tract, nervous system, mental disorders and 
metabolic disease history. 
4 Sign informed consent prior to the test and fully understand the contents, process and 
possible adverse reactions, and be able to communicate well with the researcher. 
 
Exclusion Criteria: 
1. Any clinical trials in the 90 days prior to the trial, or other clinical trials planned for the 
duration of the trial. 
2. Underwent major surgery within 90 days of the trial or planned to undergo surgery within 3 
months of the trial. 
3. Blood loss or blood donation over 300mL in the 90 days before the test. 
4. Esophageal reflux, stomach bleeding or peptic ulcer disease in the 180 days prior to the test, 
heartburn occurs more than once a week, or any surgical procedure that may affect drug 
absorption (E.G. cholecystectomy). 
5. Persons with specific allergies (asthma, urticaria, eczema, etc.) or allergies (such as those 
who are allergic to two or more medications, food or pollen), or are known to be allergic to 
the ingredients * or analogues of the drug. 
* The main components of the trial preparation: valsartan, benzene sulfonic acid amlodipine, 
microcrystalline cellulose, crosslinked povidone, crosslinked carboxymethyl cellulose 
sodium, silica, magnesium stearate, hydroxypropyl methyl cellulose, iron oxide yellow, 
polyethylene glycol, talc, Titanium dioxide; Reference Preparation main components: 
valsartan, amlodipine, microcrystalline cellulose, cross-linked povidone, silica, Magnesium 
stearate, hydroxypropyl methyl cellulose, iron oxide yellow, polyethylene glycol, talcum 
powder, Titanium Dioxide. 
6. Use of any medication within 28 days of the trial, including prescription, over-the-counter, 
and/or alternative medications (such as medicinal herbs, herbal medicines, hemostasis and 
blood-activating plants or health supplements), and the use of hormonal contraceptives or 
vaccines. 
7. A history of psychotropic substance abuse. 
8. Urine screening Positive. 
9. The average daily smoking was over 3 in the 90 days prior to the trial, alcohol consumption, 
women drinking more than 7 cups per week for 28 days or more than 14 cups per week for 
men (1 cups of =150ml wine =360ml Beer =45ml spirits). 
10. Alcohol expiratory test Positive. 
11. Body temperature (ear Temperature) ≥37.5℃, breathing is obviously abnormal and the 
researchers believe that it is not suitable to participate in the test, sitting systolic 
pressure >140mmhg or <100mmhg, sitting diastolic pressure >90mmhg or <60mmhg, 
sitting pulse 50 times/minute or > 100 Times/minute. 
12. Human immunodeficiency virus antibody (HIV-Ab), hepatitis B virus surface antigen 
(HBsAg), hepatitis C virus antibody (HCV-Ab) or Treponema pallidum antibody (TP) 
Positive. 
13.Special dietary requirements, No uniform diet during the trial. 
14. Subjects refused to comply with the drug before 48h banned caffeine, alcohol, grapefruit 

beverages and food (including tea, chocolate, coffee, coke, etc.). 
15. Participants with a companion refused to use effective contraceptive measures within 180 
days of screening to the completion of the test, as detailed in Appendix 2. 
16. Female subjects were tested positive for blood/urine pregnancy. 
17. Persons with impaired renal function, or who have suffered from urinary system disease. 
18. A History of orthostatic hypotension. 
19. fainting during venipuncture, dizzy blood and venous blood collection difficult person. 
20. The physical examination was obviously abnormal and the researchers found it 
inappropriate to participate in the trial. 
21. There was a significant abnormality in the ECG test and the researchers found it 
inappropriate to Participate. 
22. Blood biochemistry, blood routine, urine routine examination had the obvious abnormality 
and the researcher thought that was not suitable to participate in the experiment. 
23. Subjects may not be able to complete this study or other researchers ' judgment for other 
reasons. 
Note: the exclusion criteria in 1th, 2, 3, 4, 6, 9 in the time are from the first 1 days before the 
administration of the Calculation. 
 
Contacts and Locations:                                                
Locations 
China  
The 2nd Second Affiliated Hospital of WMU Phase I Clinical Trial Unit /Center Of 
Bioequivalence Study  
Wenzhou, Zhejiang, China 
Sponsors and Collaborators 
The 2nd Second Affiliated Hospital of WMU Phase I Clinical Trial Unit /Center Of 
Bioequivalence Study, China 
Hua yuan Pharmaceutical LLC, China 
Investigators 
Study Director: Ting Li, Master, The 2nd Second Affiliated Hospital of WMU Phase I 
Clinical Trial Unit /Center Of Bioequivalence Study