The PK/PD Study of SHR7280 Tablets in Healthy Subjects.

Healthy Subjects Clinical Trial

Official title:

A Randomized, Double-blind, Dose-escalation, Placebo-controlled Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Oral Doses of SHR7280 Tablets in Healthy Subjects.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04554043
• Other study ID #: SHR7280-103
• Status: Completed
• Phase: Phase 1
• Start date: September 11, 2020
• Est. completion date: September 28, 2021

Study information

• Verified date: October 2021
• Source: Jiangsu HengRui Medicine Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR7280 tablets in healthy subjects.

Description:

GNRH antagonists can be used to treat sex hormone-dependent diseases, and SHR7280 is an oral GNRH antagonist. The purpose of this study is to observe the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple oral doses of SHR7280 in healthy subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 118
• Est. completion date: September 28, 2021
• Est. primary completion date: September 28, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

PART 1:

1. Healthy males , aged 18-65;

2. BMI 18 ~ 30 kg/m2;

3. Subjects in general good health. No clinically significant findings in Physical examination and auxiliary examination.

PART 2:

1. premenopausal females, aged 18-45;

2. BMI 18 ~ 30 kg/m2;

3. Subjects in general good health. No clinically significant findings in Physical examination and auxiliary examination.

Exclusion Criteria:

PART 1

1. Testosterone (T) < 12 nmol/L;

2. ALT or AST or total bilirubin exceeds the upper limit of normal;

3. Those with positive nicotine test and alcohol breath test before administration, and those with positive drug screening before administration;

4. Use of any medication within 1 month before administration; or use of medication that does not exceed 5 half-lives, whichever is longer;

5. Subjects with chronic diseases or serious diseases that affect drug absorption, distribution, metabolism and excretion;

6. Blood donation or donation of blood components within 1 month before screening, or loss of blood equivalent to at least 200 mL, or transfusion within 2 months;

7. Use of GnRH agonists and GnRH antagonists within 6 months before screening and use of any androgens and antiandrogens within 5 half-lives before screening;

8. Subjects with severe infection, severe trauma or major surgery within 6 months before screening;

9. Positive results of infectious disease screening .

10. Allergic constitution or allergy to two or more kinds of food and drugs, including known history of allergy to the study drug or any component of the study drug.

PART 2:

1. Pregnant or breast feeding;

2. FSH=25U/L;

3. Positive serum pregnancy test (serum ß-HCG test) result;

4. Abnormal uterine bleeding within 3 months prior to screening

5. ALT or AST or total bilirubin exceeds the upper limit of normal;

6. Those with positive nicotine test and alcohol breath test before administration, and those with positive drug screening before administration;

7. Use of any medication within 1 month before administration; or use of medication that does not exceed 5 half-lives, whichever is longer;

8. Subjects with chronic diseases or serious diseases that affect drug absorption, distribution, metabolism and excretion;

9. Blood donation or donation of blood components within 1 month before screening, or loss of blood equivalent to at least 200 mL, or transfusion within 2 months;

10. GnRH agonist use 6 months prior to Screening and GnRH antagonist or any sex hormone use 2 months prior to Screening.

11. Subjects with severe infection, severe trauma or major surgery within 6 months before screening

12. Positive results of infectious disease screening .

13. Allergic constitution or allergy to two or more kinds of food and drugs, including known history of allergy to the study drug or any component of the study drug.

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• SHR7280
treatment
• Placebo oral tablet
blank control

Locations

Country	Name	City	State
China	Affiliated Hospital of Qingdao University	Qingdao	Shan Dong

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu HengRui Medicine Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse events	Part 1 and Part 2	Pre-dose to 28±2 days after dose administration
Secondary	Area under the plasma concentration versus time curve (AUCt) after the first dose of SHR7280;	Part 1 and Part 2	At pre-defined intervals from initial dose through final study visit( 28±2 days after dose administration)
Secondary	Maximum observed serum concentration (Cmax) after the first dose of SHR7280;	Part 1 and Part 2	At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
Secondary	Time to maximum observed serum concentration (Tmax) after the first dose of SHR7280;	Part 1 and Part 2	At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
Secondary	Time to elimination half-life (T1/2) ;	Part 1 and Part 2	At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
Secondary	Apparent total clearance(CL/F) of the drug from plasma after last morning dose of SHR7280;	Part 1 and Part 2	At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
Secondary	Apparent volume of distribution(Vz/F) after last morning dose of SHR7280;	Part 1 and Part 2	At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
Secondary	Maximum observed serum concentration (Cmax) after last morning dose of SHR7280;	Part 1 and Part 2	At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
Secondary	Time to maximum observed serum concentration (Tmax) after last morning dose of SHR7280;	Part 1 and Part 2	At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
Secondary	Trough observed serum concentration (Ctrough) after last morning dose of SHR7280;	Part 1 and Part 2	At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
Secondary	Accumulation Factor(Racc)after last morning dose of SHR7280;	Part 1 and Part 2	At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
Secondary	Area under the plasma concentration versus time curve (AUCt) after last morning dose of SHR7280;	Part 1 and Part 2	At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
Secondary	Endocrine Parameters: Testosterone	Part 1	At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
Secondary	Endocrine Parameters: Estuarial	Part 2	At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
Secondary	Endocrine Parameters:Progesterone	Part 2	At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
Secondary	Endocrine Parameters: Luteinizing hormone	Part 2	At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
Secondary	Endocrine Parameters: Follicle stimulating hormone	Part 2	At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)