The Pharmacokinetic(PK)/Pharmacodynamics(PD) Study of SHR7280 Tablets in Premenopausal Subjects With Endometriosis.

A Phase I/II, Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics ,Pharmacodynamics and Efficacy of SHR7280 Tablets in Premenopausal Subjects With Endometriosis.

The primary objective of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR7280 tablets in premenopausal subjects with endometriosis. In addition, this study will provide information on efficacy of SHR7280 tablets in premenopausal subjects with endometriosis.

Study Overview

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

Detailed Description

Endometriosis is a common disease, affecting 5-10% of women of reproductive age . It is an estrogen-dependent and estrogen-driven disease and so hormonal manipulation and suppression of estrogen production form the basis of the majority of medical treatment. The primary objective of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR7280 tablets in premenopausal subjects with endometriosis. In addition, this study will provide information on efficacy of SHR7280 tablets in premenopausal subjects with endometriosis.

• Study Type: Interventional
• Enrollment (Actual): 179
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Peking, Beijing, China
      • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Phase I/II

1. premenopausal females, aged 18-45
2. History of regular menstrual cycles
3. Endometriosis participant diagnosed by surgical (e.g., laparoscopy or laparotomy) or by magnetic resonance imaging or ultrasonography.
4. Participant must agree to use only protocol specified rescue analgesics during the Screening and Treatment Periods for endometriosis-associated pain.
5. Participant in general good health. No clinically significant findings in laboratory parameters or clinically significant abnormality on X-ray Phase I (only) Participant has mild or moderate pelvic pain associated with endometriosis at Screening.

Phase II(only) Participant has moderate or severe pelvic pain associated with endometriosis at Screening.

Exclusion Criteria:

Phase I/II

1. Subjects with severe trauma or surgery within 6 months prior to the screening；
2. Known blood donation within 30 days pre-dose; donating≥200 ml of blood 2 months pre-dose;
3. Pregnant or Serum β-human chorionic gonadotropin (hCG)> 5 Million International Units(mIU)/mL at screening or baseline
4. Pregnant or breast feeding ;
5. Have pelvic pain that is not caused by endometriosis
6. Abnormal uterine bleeding
7. Are currently receiving gonadotropin-releasing hormone (GnRH) agonist, a GnRH antagonist or danazol or have received any of these agents within 6 months of the start of screening.
8. Are currently receiving subcutaneous medroxyprogesterone acetate (DMPA-SC) or intramuscular medroxyprogesterone acetate (DMPA-IM) or have received any of these agents within 3 months of the start of screening.
9. Are currently using hormonal contraception or other forms of hormonal therapy or received such treatment within 2 months of the start of screening.

Phase I (only) one month prior to screening involved in any drug or medical device clinical subjects, or within 5 half-life of drugs before screening; Phase II (only) Screening dual-energy x-ray absorptiometry (DXA) scan results of the lumbar spine, femoral neck, or total hip bone mineral density corresponding to 1.5 or more standard deviations below normal (T-score at or below -1.5)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR7280 dose 1; oral administration for 21days,Phase I	Drug: SHR7280; treatment; Drug: Placebo oral tablet; blank control
Experimental: SHR7280 dose 2; oral administration for 21days,Phase I	Drug: SHR7280; treatment; Drug: Placebo oral tablet; blank control
Experimental: SHR7280 dose 3; oral administration for 21days,Phase I	Drug: SHR7280; treatment; Drug: Placebo oral tablet; blank control
Experimental: SHR7280 dose 4; oral administration for 21days,Phase I	Drug: SHR7280; treatment; Drug: Placebo oral tablet; blank control
Active Comparator: SHR7280 low dose; oral administration for 84days,Phase II	Drug: SHR7280; treatment
Active Comparator: SHR7280 high dose; oral administration for 84days, Phase II	Drug: SHR7280; treatment
Placebo Comparator: Placebo; oral administration for 84days, Phase II	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	Phase I	Pre-dose to 28±2 days after dose administration
Change From Baseline in the 7-day mean score for pelvic pain as measured by VAS at weeks 12	Phase II daily assessment of dysmenorrhea score on a 4-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe) using an e-Diary.	Baseline and weeks 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK markers of SHR7280: area under the plasma concentration versus time curve (AUC)	Phase I & II	At pre-defined intervals from initial dose through final study visit
PK markers of SHR7280: time to maximum plasma concentration(Tmax)	Phase I & II	At pre-defined intervals from initial dose through final study visit
PK markers of SHR7280: maximum plasma concentration(Cmax)	Phase I & II	At pre-defined intervals from initial dose through final study visit
PK markers of SHR7280: half-time(t1/2)	Phase I & II	At pre-defined intervals from initial dose through final study visit
PK markers of SHR7280: apparent clearance(CL/F)	Phase I & II	At pre-defined intervals from initial dose through final study visit
PK markers of SHR7280: apparent volume of distribution(Vz/F)	Phase I & II	At pre-defined intervals from initial dose through final study visit
PD markers of SHR7280: Concentration of Estradiol(E2)	Phase I & II	At pre-defined intervals from initial dose through final study visit
PD markers of SHR7280: Concentration of Progesterone(P)	Phase I & II	At pre-defined intervals from initial dose through final study visit
PD markers of SHR7280: Concentration of Follicle stimulating hormone(FSH)	Phase I & II	At pre-defined intervals from initial dose through final study visit
PD markers of SHR7280: Concentration of Luteinizing hormone(LH)	Phase I & II	At pre-defined intervals from initial dose through final study visit
Change From Baseline in the 7-day mean score for pelvic pain as measured by VAS	Phase II	Baseline and weeks 4、8
Change From Baseline in the Monthly Mean score for pelvic pain as measured by VAS	Phase II	Baseline and weeks 4、8、12
Change From Baseline in the Monthly Mean Dysmenorrhea Score	Phase II	Baseline and weeks 8、12
Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score and Dyspareunia Score	Phase II	Baseline and weeks 4、8、12
Change from baseline to monthly analgesic use to treat endometriosis-associated pain	Phase II	Baseline and weeks 4、8、12
Patient Global Impression of Change (PGIC) score at week 12	Phase II	Week 12
Adverse events		during Pre and 28±3 days after dose administration

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Hongyan Guo, PhD, Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2020
• Primary Completion (Actual): May 14, 2024
• Study Completion (Actual): May 14, 2024

Study Registration Dates

• First Submitted: May 21, 2020
• First Submitted That Met QC Criteria: June 2, 2020
• First Posted (Actual): June 5, 2020

Study Record Updates

• Last Update Posted (Actual): July 8, 2024
• Last Update Submitted That Met QC Criteria: July 4, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Endometriosis
• Other Study ID Numbers: SHR7280-102

Drug and device information, study documents

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