Tolerability and Pharmacokinetics of CSPCHA115 Capsules in Chinese Healthy Volunteers

Asthma; Allergic Rhinitis Clinical Trial

Official title:

A Phase I, Ascending Multiple-dose Clinical Trial of CSPCHA115 Capsules to Evaluate the Tolerability and Pharmacokinetics in Chinese Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04161547
• Other study ID #: HA116201903/PRO I-MAD
• Status: Completed
• Phase: Phase 1
• Start date: December 12, 2019
• Est. completion date: June 1, 2020

Study information

• Verified date: April 2021
• Source: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A randomized, single-center, double-blind, ascending multiple-dose, placebo-controlled study to evaluate the tolerability and pharmacokinetics of CSPCHA115 capsules in Chinese healthy volunteers.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: June 1, 2020
• Est. primary completion date: June 1, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• 18 = age = 45 years old, male or female;

• Bodyweight=45.0 kg (female) or 50.0 kg (male), 19 kg/m^2 = Body Mass Index(BMI )= 26 kg/m^2;

• The female subjects are not during pregnancy or lactation; the male subjects have no sperm donation plan from the signing of the informed consent form to 1 month after the completion of the study. The subjects and their partners agree to use effective non-hormonal contraceptives (such as condoms, drug-free IUDs, etc.) from the day signing the informed consent form to 1 month after the completion of the study, or had taken permanent contraceptives (such as bilateral tubal ligation, vasectomy, etc.);

• Subjects voluntarily sign the informed consent form, and are able to complete the trial according to the protocol;

Exclusion Criteria:

Those who conform to one of the following provisions shall not be included in the group;

• A clear history of neurological or mental disorders (including seizures, dementia, depression or biphasic affective disorders, etc.); immunodeficient or immunosuppressive diseases, malignant tumor diseases; cardiovascular, liver and kidney, endocrine, respiratory, blood, digestive system and other chronic diseases;

• Subjects who underwent large surgical operations within 6 months before signing the informed consent (such as coronary artery bypass grafting, hepatorenectomy, nephrectomy, gynecological surgery, etc.), and those with acute neurological, digestive, respiratory, circulation, endocrine, blood and other systemic diseases within 3 months before signing the informed consent form may affect the absorption, distribution, metabolism and excretion of drugs;

• Subjects with allergic constitutions, or who are allergic to more than 1 drug, or had other known serious allergic reactions;

• Subjects who did not meet the health criteria during the screening period, including abnormal vital signs; QTc interval = 450 ms (male) or 470ms (female), prolongation of QTc interval, or other abnormal clinical significance of electrocardiogram (ECG); the results of physical examination, laboratory examination and so on are abnormal and have clinical significance.

• One of hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (Anti-HCV), human immunodeficiency virus antibody (Anti-HIV) and Treponema pallidum antibody (Anti-TP) was positive;

• Any prescription drugs, non-prescription drugs, biological products, the Chinese patent medicines, herbs, vitamin dietary supplements, and health-care products (other than external use), oral long-acting contraceptives or embedded long-acting contraceptives were used regularly within 2 weeks before the signing of the informed consent form;

• A history of alcoholism, or alcohol test positive at screening;

• The average daily smoking volume was more than 5 within 6 months before signing the informed consent form;

• Drug abuse within 1 year before signing the informed consent form, or urine test positive for drugs at screening;

• Subjects who were accustomed to excessive caffeine drinks or foods that may affect drug metabolism within 4 weeks prior to the signing of the informed consent form;

• Subjects who lost blood or donated more than 200 ml within 8 weeks before signing the informed consent form, or who planned to donate blood within 1 month after the completion of the study;

• Subjects who plan to undergo surgery during the trial period, or those who plan to take part in strenuous exercise during the trial period;

• Subjects who are participating in other clinical trials, or who have participated in clinical trial about any other drugs or devices within 3 months before signing the informed consent form;

• Not suitable for this clinical trial judged by the investigators.

Related Conditions & MeSH terms

• Asthma; Allergic Rhinitis
• Rhinitis
• Rhinitis, Allergic

Intervention

Drug:
• CSPCHA115 100 mg; Matching placebo 100 mg
CSPCHA115 100 mg once daily in the fasted state for 7 days; Matching placebo 100 mg once daily in the fasted state for 7 days.
• CSPCHA115 200 mg; Matching placebo 200 mg
CSPCHA115 200 mg once daily in the fasted state for 7 days; Matching placebo 200 mg once daily in the fasted state for 7 days.
• CSPCHA115 400 mg; Matching placebo 400 mg
CSPCHA115 400 mg once daily in the fasted state for 7 days; Matching placebo 400 mg once daily in the fasted state for 7 days.
• CSPCHA115 600 mg; Matching placebo 600 mg
CSPCHA115 600 mg once daily in the fasted state for 7 days; Matching placebo 600 mg once daily in the fasted state for 7 days.

Locations

Country	Name	City	State
China	Beijing Anzhen Hospital, Capital Medical University	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number and incidence of subjects with Adverse Events (AEs)	To evaluate the safety and tolerability after repeated administrations of CSPCHA115 capsules 100, 200, 400 and 600 mg	12 days after drug administration
Primary	Number of subjects with clinically significant symptoms abnormalities	To evaluate the safety and tolerability after repeated administrations of CSPCHA115 capsules 100, 200, 400 and 600 mg	10 days after drug administration
Primary	Number of subjects with clinically significant vital sign abnormalities	To evaluate the safety and tolerability after repeated administrations of CSPCHA115 capsules 100, 200, 400 and 600 mg	10 days after drug administration
Primary	Number of subjects with clinically significant physical examination abnormalities	To evaluate the safety and tolerability after repeated administrations of CSPCHA115 capsules 100, 200, 400 and 600 mg	10 days after drug administration
Primary	Number of subjects with clinically significant laboratory abnormalities	To evaluate the safety and tolerability after repeated administrations of CSPCHA115 capsules 100, 200, 400 and 600 mg	10 days after drug administration
Primary	Number of subjects with clinically significant electrocardiograms (ECGs) abnormalities	To evaluate the safety and tolerability after repeated administrations of CSPCHA115 capsules 100, 200, 400 and 600 mg	10 days after drug administration
Primary	Time to reach maximum observed concentration (Tmax)	To evaluate the pharmacokinetics after repeated administrations of CSPCHA115 capsules 100, 200, 400 and 600 mg	Day 1(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours); Day 5(Pre-dose); Day 6(Pre-dose); Day 7(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours) after drug administration
Primary	Maximum observed concentration (Cmax)	To evaluate the pharmacokinetics after repeated administrations of CSPCHA115 capsules 100, 200, 400 and 600 mg	Day 1(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours); Day 5(Pre-dose); Day 6(Pre-dose); Day 7(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours) after drug administration
Primary	Area under the concentration-time curve from time 0 to 24h (AUC0-24h)	To evaluate the pharmacokinetics after repeated administrations of CSPCHA115 capsules 100, 200, 400 and 600 mg	Day 1(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours); Day 5(Pre-dose); Day 6(Pre-dose); Day 7(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours) after drug administration
Primary	Tmax at steady state (Tss max)	To evaluate the pharmacokinetics after repeated administrations of CSPCHA115 capsules 100, 200, 400 and 600 mg	Day 1(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours); Day 5(Pre-dose); Day 6(Pre-dose); Day 7(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours) after drug administration
Primary	Cmax at steady state (Css max)	To evaluate the pharmacokinetics after repeated administrations of CSPCHA115 capsules 100, 200, 400 and 600 mg	Day 1(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours); Day 5(Pre-dose); Day 6(Pre-dose); Day 7(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours) after drug administration
Primary	Cmin at steady state (Css min)	To evaluate the pharmacokinetics after repeated administrations of CSPCHA115 capsules 100, 200, 400 and 600 mg	Day 1(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours); Day 5(Pre-dose); Day 6(Pre-dose); Day 7(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours) after drug administration
Primary	Average concentration at steady state (Css av)	To evaluate the pharmacokinetics after repeated administrations of CSPCHA115 capsules 100, 200, 400 and 600 mg	Day 1(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours); Day 5(Pre-dose); Day 6(Pre-dose); Day 7(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours) after drug administration
Primary	AUC at steady state (AUCss)	To evaluate the pharmacokinetics after repeated administrations of CSPCHA115 capsules 100, 200, 400 and 600 mg	Day 1(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours); Day 5(Pre-dose); Day 6(Pre-dose); Day 7(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours) after drug administration
Primary	Elimination half-life (t1/2)	To evaluate the pharmacokinetics after repeated administrations of CSPCHA115 capsules 100, 200, 400 and 600 mg	Day 1(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours); Day 5(Pre-dose); Day 6(Pre-dose); Day 7(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours) after drug administration
Primary	Apparent clearance at steady state (CLss/F)	To evaluate the pharmacokinetics after repeated administrations of CSPCHA115 capsules 100, 200, 400 and 600 mg	Day 1(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours); Day 5(Pre-dose); Day 6(Pre-dose); Day 7(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours) after drug administration
Primary	Apparent volume of distribution (Vz/F)	To evaluate the pharmacokinetics after repeated administrations of CSPCHA115 capsules 100, 200, 400 and 600 mg	Day 1(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours); Day 5(Pre-dose); Day 6(Pre-dose); Day 7(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours) after drug administration
Primary	Fluctuation coefficient (DF)	To evaluate the pharmacokinetics after repeated administrations of CSPCHA115 capsules 100, 200, 400 and 600 mg	Day 1(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours); Day 5(Pre-dose); Day 6(Pre-dose); Day 7(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours) after drug administration
Primary	Accumulation ratio (Rac)	To evaluate the pharmacokinetics after repeated administrations of CSPCHA115 capsules 100, 200, 400 and 600 mg	Day 1(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours); Day 5(Pre-dose); Day 6(Pre-dose); Day 7(Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours) after drug administration