Population Pharmacokinetic - Pharmacodynamic Models of Chronic Disease Therapeutics for Smokers

Purpose of study: Establishing population pharmacokinetic - pharmacodynamic models of chronic disease therapeutics for smoking patients to investigate the effects of gender, age, body weight, liver function, kidney function, nicotine, polycyclic aromatic hydrocarbon related metabolic enzymes and drug related metabolic enzymes gene polymorphism on steady-state drug concentration and efficacy in chronic smoking patients after taking drugs.

Object of study: Smoking and non-smoking patients taking levamlodipine besylate tablets or metformin sustained-release tablets.

Study Overview

• Status: Recruiting
• Conditions: Smoking; Chronic Disease
• Intervention / Treatment: Behavioral: Smoking; Behavioral: non-somking

Detailed Description

Purpose of study: Establishing population pharmacokinetic - pharmacodynamic modes of chronic disease therapeutics for smoking patients to investigate the effects of gender, age, body weight, liver function, kidney function, nicotine, polycyclic aromatic hydrocarbon related metabolic enzymes and drug related metabolic enzymes gene polymorphism on steady-state drug concentration and efficacy in chronic smoking patients after taking drugs.

Object of study: Smoking and non-smoking patients taking Levamlodipine besylate tablets or metformin sustained-release tablets.

Parameters of study： PK parameters: drug plasma concentration. PD parameters: blood pressure or blood sugar. covariates: Gender, age, height, weight, BMI, liver function (ALT, AST, TP, TBIL), kidney function (Scr, UA, UREA), nicotine plasma concentration, cigarette related metabolic enzyme gene (CYP1A1, CYP1A2) polymorphism and drug-related metabolic enzyme gene (CYP3A4, CYP3A5, MATE1), MARE2, OCT2) polymorphism, etc.

Safety : adverse events occurred during the test.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Yu Xian; Phone Number: 18512356862; Email: 1clinicaltrial@hospital.cqmu.edu.cn

Study Locations

• China
  • Chongqing, China
    • Recruiting
    • Yu Xian
    • Contact: Yu Xian, Doctor; Phone Number: 18512356862; Email: 1clinicaltrial@hospital.cqmu.edu.cn
    • Sub-Investigator: Li Guoxing

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Subjects were mainly selected for outpatient follow-up

Description

Inclusion Criteria:

According to the selection criteria for non-smokers:

No previous smoking history;Or previous smokers who had quit smoking for more than 6 months prior to enrollment.

A smoker joins the queue by:

1. Have smoked for more than one year (more than one cigarette per day on average and more than six months continuously) and have not quit at present.
2. Agree to smoke cigarettes sold in the market according to the requirements of the program.

Both smokers and non-smokers were forced to meet additional inclusion criteria at the cost of a smoker:

1. Age: 18-70 (boundary value included), no gender limitation;

2. Patients who meet one of the following conditions:

   ① Patients who were previously diagnosed with hypertension, were taking levamlodipine besylate tablets for antihypertensive therapy, and were managed according to hypertensive lifestyle (diet and exercise) for a long time.

   ② Patients who were previously diagnosed with type 2 diabetes, were taking metformin sustained-release tablets for hypoglycemic treatment, and were managed according to diabetic lifestyle (diet and exercise) for a long time.

3. Fixed dosing regimen was used one month before enrollment, and the regimen could be continued after enrollment.
4. Subjects understand the risks and regulations of the study and can abide by the study protocol, voluntarily participate in the study and sign the informed consent.

Exclusion Criteria:

1. Have a history of alcohol abuse (drinking more than 14 units of alcohol per week, 1 unit =350 mL beer or 44 mL 40% alcohol spirits or 150 mL wine) or have a history of alcohol abuse and have been abstinent for less than 3 months.
2. The subject has a history of pathophysiological conditions affecting drug absorption (such as inability to swallow, vomiting, diarrhea, etc.) or gastrointestinal surgery affecting drug absorption.
3. HBsAg, HCV or syphilis antibody tested positive in the past.
4. Pregnant and lactating women.
5. The investigator considers that the subjects are not suitable to participate in this study due to safety or compliance factors.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Smoker with taking levamlodipine besylate tablets; The subjects are allowed to smoke during the time taking levamlodipine besylate tablets.	Behavioral: Smoking; The Study contains patients who are allowed to smoke
Non-smoker with taking levamlodipine besylate tablets; The subjects are not allowed to smoke during the time taking levamlodipine besylate tablets.	Behavioral: non-somking; The Study contains patients who are not allowed to smoke
Smoker with taking metformin sustained-release tablets; The subjects are allowed to smoke during the time taking metformin sustained-release tablets。	Behavioral: Smoking; The Study contains patients who are allowed to smoke
Non-smoker with taking metformin sustained-release tablets; The subjects are not allowed to smoke during the time taking metformin sustained-release tablets.	Behavioral: non-somking; The Study contains patients who are not allowed to smoke

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug plasma steady state concentrations	drug plasma steady state concentrations are regard as the PK parameters	Blood samples were collected 30 minutes before administration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure levels	Blood pressure levels are regard as the PD parameters	Blood pressure levels were collected 30 minutes before administration
Blood glucose levels	Blood glucose levels are regard as the PD parameters	Blood glucose levels were collected 30 minutes before administration

Collaborators and Investigators

• Sponsor: The Second Affiliated Hospital of Chongqing Medical University
• Investigators: Principal Investigator: Yu Xian, The Second Affiliated Hospital of Chongqing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2022
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: November 2, 2021
• First Submitted That Met QC Criteria: November 16, 2021
• First Posted (Actual): November 19, 2021

Study Record Updates

• Last Update Posted (Estimated): June 16, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Smoking; Gene polymorphism; Population Pharmacokinetics/ Pharmacodynamics
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Chronic Disease
• Other Study ID Numbers: 2021LCYJ040

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