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

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.

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

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: SHR7280; Drug: Placebo oral tablet

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.

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shan Dong
    • Qingdao, Shan Dong, China, 266000
      • Affiliated Hospital of Qingdao University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR7280 dose 1(male); oral administration for 14 days,Phase I(PART 1)	Drug: SHR7280; treatment; Drug: Placebo oral tablet; blank control
Experimental: SHR7280 dose 2(male); oral administration for 14 days,Phase I(PART 1)	Drug: SHR7280; treatment; Drug: Placebo oral tablet; blank control
Experimental: SHR7280 dose 3(male); oral administration for 14 days,Phase I(PART 1)	Drug: SHR7280; treatment; Drug: Placebo oral tablet; blank control
Experimental: SHR7280 dose 4(male); oral administration for 14 days,Phase I(PART 1)	Drug: SHR7280; treatment; Drug: Placebo oral tablet; blank control
Experimental: SHR7280 dose 5(male); oral administration for 14 days,Phase I(PART 1)	Drug: SHR7280; treatment; Drug: Placebo oral tablet; blank control
Experimental: SHR7280 dose 1(female); oral administration for 21 days,Phase I(PART 2)	Drug: SHR7280; treatment; Drug: Placebo oral tablet; blank control
Experimental: SHR7280 dose 2(female); oral administration for 21 days,Phase I(PART 2)	Drug: SHR7280; treatment; Drug: Placebo oral tablet; blank control
Experimental: SHR7280 dose 3(female); oral administration for 21 days,Phase I(PART 2)	Drug: SHR7280; treatment; Drug: Placebo oral tablet; blank control
Experimental: SHR7280 dose 4(female); oral administration for 21 days,Phase I(PART 2)	Drug: SHR7280; treatment; Drug: Placebo oral tablet; blank control
Experimental: SHR7280 dose 6(male); oral administration for 14 days,Phase I(PART 1)	Drug: SHR7280; treatment; Drug: Placebo oral tablet; blank control
Experimental: SHR7280 dose 7(male); oral administration for 14 days,Phase I(PART 1)	Drug: SHR7280; treatment; Drug: Placebo oral tablet; blank control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse events	Part 1 and Part 2	Pre-dose to 28±2 days after dose administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration versus time curve (AUCτ) 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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
Area under the plasma concentration versus time curve (AUCτ) 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)
Endocrine Parameters: Testosterone	Part 1	At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
Endocrine Parameters: Estuarial	Part 2	At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
Endocrine Parameters:Progesterone	Part 2	At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
Endocrine Parameters: Luteinizing hormone	Part 2	At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)
Endocrine Parameters: Follicle stimulating hormone	Part 2	At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration)

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Yu Cao, PhD, Hospital of Qingdao University

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2020
• Primary Completion (Actual): September 28, 2021
• Study Completion (Actual): September 28, 2021

Study Registration Dates

• First Submitted: August 31, 2020
• First Submitted That Met QC Criteria: September 12, 2020
• First Posted (Actual): September 18, 2020

Study Record Updates

• Last Update Posted (Actual): October 28, 2021
• Last Update Submitted That Met QC Criteria: October 21, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: SHR7280-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Hengrui shall own the exclusive rights to all results, data, findings, radiological & diagnostic images, discoveries, inventions & specifications, whether patentable or not, that are originated, conceived, derived, produced, discovered, invented or otherwise made by Center, PI and/or Study Team Physicians and/or Members in connection with the performance of the Study (i.e. Results).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No