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

Endometriosis Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04417972
• Other study ID #: SHR7280-102
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 30, 2020
• Est. completion date: January 30, 2024

Study information

• Verified date: May 2022
• Source: Jiangsu HengRui Medicine Co., Ltd.
• Contact: Zhenyi Zhu, M.D
• Phone: +86 0518-82342973
• Email: zhenyi.zhu[@]hengrui.com
• 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 premenopausal subjects with endometriosis. In addition, this study will provide information on efficacy of SHR7280 tablets in premenopausal subjects with endometriosis.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 207
• Est. completion date: January 30, 2024
• Est. primary completion date: January 30, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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 ß-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)

Related Conditions & MeSH terms

• Endometriosis

Intervention

Drug:
• SHR7280
treatment
• Placebo oral tablet
blank control

Locations

Country	Name	City	State
China	Peking University Third Hospital	Peking	Beijing

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