Clinical trial NCT04554043: The PK/PD Study of SHR7280 Tablets in Healthy Subjects.
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-09-18
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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 β-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.

Primary outcomes:
measure: Number of Participants with Adverse events
timeFrame: Pre-dose to 28±2 days after dose administration
Secondary outcomes:
measure: Area under the plasma concentration versus time curve (AUCτ) after the first dose of SHR7280;
timeFrame: At pre-defined intervals from initial dose through final study visit( 28±2 days after dose administration)
measure: Maximum observed serum concentration (Cmax) after the first dose of SHR7280;
timeFrame: At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
measure: Time to maximum observed serum concentration (Tmax) after the first dose of SHR7280;
timeFrame: At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
measure: Time to elimination half-life (T1/2) ;
timeFrame: At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
measure: Apparent total clearance(CL/F) of the drug from plasma after last morning dose of SHR7280;
timeFrame: At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
measure: Apparent volume of distribution(Vz/F) after last morning dose of SHR7280;
timeFrame: At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
measure: Maximum observed serum concentration (Cmax) after last morning dose of SHR7280;
timeFrame: At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
measure: Time to maximum observed serum concentration (Tmax) after last morning dose of SHR7280;
timeFrame: At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
measure: Trough observed serum concentration (Ctrough) after last morning dose of SHR7280;
timeFrame: At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
measure: Accumulation Factor（Racc）after last morning dose of SHR7280;
timeFrame: At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
measure: Area under the plasma concentration versus time curve (AUCτ) after last morning dose of SHR7280;
timeFrame: At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
measure: Endocrine Parameters: Testosterone
timeFrame: At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
measure: Endocrine Parameters: Estuarial
timeFrame: At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
measure: Endocrine Parameters:Progesterone
timeFrame: At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
measure: Endocrine Parameters: Luteinizing hormone
timeFrame: At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
measure: Endocrine Parameters: Follicle stimulating hormone
timeFrame: At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
Other outcomes:
Locations:
city: Qingdao
country: China
facility: Affiliated Hospital of Qingdao University
state: Shan Dong
Study officials:
affiliation: Hospital of Qingdao University
name: Yu Cao, PhD
role: PRINCIPAL_INVESTIGATOR
References: