Clinical trial NCT03922373: A Study of Benzonatate Soft Capsule in Chinese Healthy Subjects
Official title: The Single-dose and Multiple-dose Pharmacokinetic Study of Benzonatate Soft Capsule in Chinese Healthy Subjects
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Cough
Lead sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-04-19
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Objective to study the pharmacokinetic, safety and efficacy of Single-dose and multiple-dose of benzonatate in Chinese healthy male and female subjects.

Detailed description: Objective to study the pharmacokinetic, safety and efficacy of Single-dose and multiple-dose of benzonatate in Chinese healthy male and female subjects. The study was designed to be single-center, open, and parallel, there are 3 groups A, B, C, each group will be enrolled in 12 healthy adult subjects. Single-dose of pharmacokinetics will be carried out in group A and C, single-dose and multiple-dose of pharmacokinetics will be carried out in group B. Subjects in group A and C will be given benzonatate of 100mg and 400mg respectively, Subjects in group B will be given benzonatate of 200mg. Subjects in group A and C will be given benzonatate once after a 10-hour fast in the first day of the trail. Subjects in group B will be given benzonatate once after a 10-hour fast in the first day of the trail, and they will be given benzonatate thrice in the second and third day of the trail, in the fourth day, they will be given benzonatate once after a 10-hour fast. After completing blood collection and safety inspection at the appropriate time points, subjects can leave the test center. The main pharmacokinetic parameters will be calculated, to fully reflect the characteristics of drug absorption, distribution, metabolism and excretion in human body. The main pharmacokinetic parameters include Tmax, Cmax, Css, AUC0-t, AUC0-∞, λz, t1/2, Vd/F, CL/F, and so on.

Eligibility criteria: Inclusion Criteria:

* 1. You should fully understand the testing content, process and adverse reaction. Freely given informed consent.

  2. Male or Female ages 18 through 45 (include 18 and 45).

  3. The male subjects weighed more than 50 kg, the female subjects weighed more than 45kg. Body Mass Index(BMI) between 18 and 28, BMI=Weight(kg)/Height2(m2).

Exclusion Criteria:

* 1. Allergy to benzonatate, allergic constitution (Allergic to a variety of medicines and foods).

  2. Abnormal physical examination and abnormal vital signs, and have clinical significance.

  3. Abnormal results of laboratory studies and have clinical significance. 4. Abnormal electrocardiogram and have clinical significance. 5. The hepatitis B surface antigen(HbsAg), hepatitis C antibody, HIV antibody and antigen, Treponema pallidum antibody（TP-Ab）were positive.

  6. Patients with cardiovascular system, urinary system, digestive system, nervous system, respiratory system, mental or immunodeficiency diseases.

  7. Dysphagia or with gastrointestinal history influencing drug absorption. 8. Patients with any diseases that increase the risk of bleeding (e.g. acute gastritis, duodenal ulcer, and so on).

  9. Patients smoked more than 5 cigarettes a day in the first 3 months of screening 10. Alcohol breath test were positive (blood-alcohol concentration\>0.0mg/100ml) , or have history of alcoholism (more than 14 units of alcohol every week, 1 unit is equal to 285ml of beer, 25ml of spririts, or 100ml of wine.

  11. Drug abuse screening were positive by urinalysis, or have a history of substance abuse or taken drugs last 3 years.

  12. Subjects (or his fere) have family planning in the next 3 months, or can't take effective contraceptive measures in the next 3 months.

  13. Female subjects during lactation, the quantitative of β-HCG exceed the upper limit of normal range.

  14. Donate blood or massive blood loss (\>450ml) in the first 3 months of screening.

  15. Taken any drugs that can inhibit the activity of liver enzyme in the first 28 days of screening, or taken the inhibitor or inducer of CYP3A4, P-gp, Bcrp, such as Itraconazole, Ketoconazole, Dronedarone.

  16. Taken any prescription drugs, OTC, vitamin products or Chinese herbal medicine in the first 14 days of screening.

  17. Special diets (e.g. pitaya, mango, pomelo) or strenuous exercise in the first 14 days of screening, or other factors to influence drug absorption, distribution, metabolism and excretion.

  18. Have attended clinical trial in the first 3 months of screening 19. The patient can't finish the study according to protocol requirements. 20. Acute disease or simultaneous medication between screening stage and the first time taking study drugs.

  21. Have consumed any alcoholic or caffeinated food or beverage such as chocolate and coffee in the first 48 hours of taking the study drug.

  22. Investigator believes other factors not suitable for testing.

Primary outcomes:
measure: Tmax
timeFrame: day 1 and day 4
measure: Cmax
timeFrame: day 1 and day 4
measure: t1/2
timeFrame: day 1 and day 4
measure: AUC0-t
timeFrame: day 1 and day 4
measure: AUC0-∞
timeFrame: day 1 and day 4
measure: CL/F
timeFrame: day 1 and day 4
Secondary outcomes:
Other outcomes:
Locations:
city: Shijiazhuang
country: China
facility: Cspc Nbp Pharmaceutical.Co.Ltd
state: Hebei
Study officials:
affiliation: Beijing Anzhen Hospital
name: Yang Lin, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Anzhen Hospital
name: Shan Jing, M.D.
role: PRINCIPAL_INVESTIGATOR
References: