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) (ABSVAFVATVAT)

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)

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).

Study Overview

• Status: Unknown
• Conditions: Healthy
• Intervention / Treatment: Drug: Valsartan and Amlodipine Tablets

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 Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325000
      • The 2nd Second Affiliated Hospital of WMU Phase I Clinical Trial Unit /Center Of Bioequivalence Study

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male or non-pregnant non-lactating female, age 18 to 45 years, including the critical value.
• Male weight ≥ 50kg, female weight ≥ 45kg, body mass index (BMI) between 19 and 28kg / m2, including the critical value.
• Good health, no heart, liver, kidney, digestive tract, nervous system, mental disorders and metabolic disease history.
• 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:

• Any clinical trials in the 90 days prior to the trial, or other clinical trials planned for the duration of the trial.
• Underwent major surgery within 90 days of the trial or planned to undergo surgery within 3 months of the trial.
• Blood loss or blood donation over 300mL in the 90 days before the test.
• 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).

• 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.
• 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.
• A history of psychotropic substance abuse.
• Urine screening Positive.
• 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).
• Alcohol expiratory test Positive.
• 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.
• Human immunodeficiency virus antibody (HIV-Ab), hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibody (HCV-Ab) or Treponema pallidum antibody (TP) Positive.
• Special dietary requirements, No uniform diet during the trial.
• Subjects refused to comply with the drug before 48h banned caffeine, alcohol, grapefruit beverages and food (including tea, chocolate, coffee, coke, etc.).
• 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.
• Female subjects were tested positive for blood/urine pregnancy.
• Persons with impaired renal function, or who have suffered from urinary system disease.
• A History of orthostatic hypotension.
• fainting during venipuncture, dizzy blood and venous blood collection difficult person.
• The physical examination was obviously abnormal and the researchers found it inappropriate to participate in the trial.
• There was a significant abnormality in the ECG test and the researchers found it inappropriate to Participate.
• Blood biochemistry, blood routine, urine routine examination had the obvious abnormality and the researcher thought that was not suitable to participate in the experiment.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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; 1 tablet contains Valsartan 80mg& Amlodipine 5mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Bioequivalence based on Cmax	Up to 96 hours post dose in each treatment period
Bioequivalence based on AUC parameters	Up to 96 hours post dose in each treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with adverse events (AE)s	Safety and tolerability parameters will include recording of AEs(blood biochemistry, urine routine examination, electrocardiograph, etc.)	Up to 96 hours post dose in each treatment period
blood pressure	Vital sign measurement will include blood pressure	Up to 96 hours post dose in each treatment period
pulse rate	Vital sign measurement will include pulse rate	Up to 96 hours post dose in each treatment period
respiration rate	Vital sign measurement will include respiration rate	Up to 96 hours post dose in each treatment period
ear temperature	Vital sign measurement will include ear temperature	Up to 96 hours post dose in each treatment period
complete blood count	Clinical laboratory tests will include CBC	Up to 96 hours post dose in each treatment period

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Wenzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2018
• Primary Completion (Actual): November 28, 2018
• Study Completion (Anticipated): December 26, 2019

Study Registration Dates

• First Submitted: October 17, 2018
• First Submitted That Met QC Criteria: September 8, 2019
• First Posted (Actual): September 11, 2019

Study Record Updates

• Last Update Posted (Actual): September 11, 2019
• Last Update Submitted That Met QC Criteria: September 8, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Amlodipine; Valsartan; Amlodipine, Valsartan Drug Combination
• Other Study ID Numbers: 2018-10-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No