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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SHR7280 dose 1 | Experimental | oral administration for 21days,Phase I |
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| SHR7280 dose 2 | Experimental | oral administration for 21days,Phase I |
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| SHR7280 dose 3 | Experimental | oral administration for 21days,Phase I |
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| SHR7280 dose 4 | Experimental | oral administration for 21days,Phase I |
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| SHR7280 low dose | Active Comparator | oral administration for 84days,Phase II |
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| SHR7280 high dose | Active Comparator | oral administration for 84days, Phase II |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SHR7280 | Drug | treatment |
|
| 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 |
| 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) |
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Inclusion Criteria:
Phase I/II
Phase II(only) Participant has moderate or severe pelvic pain associated with endometriosis at Screening.
Exclusion Criteria:
Phase I/II
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)
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| Name | Affiliation | Role |
|---|---|---|
| Hongyan Guo, PhD | Peking University Third Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University Third Hospital | Beijing | Beijing Municipality | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37838623 | Derived | Li Y, Zheng Y, Xu B, Cai L, Feng S, Liu Y, Zhu Z, Yu Q, Guo H. Safety, Pharmacokinetics, and Pharmacodynamics of SHR7280, a Non-peptide GnRH Antagonist in Premenopausal Women with Endometriosis: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Study. Clin Pharmacokinet. 2023 Dec;62(12):1739-1748. doi: 10.1007/s40262-023-01315-6. Epub 2023 Oct 14. |
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| ID | Term |
|---|---|
| D004715 | Endometriosis |
| ID | Term |
|---|---|
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| Placebo | Placebo Comparator | oral administration for 84days, Phase II |
|
| Placebo oral tablet | Drug | blank control |
|
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 |
| D000091662 | Genital Diseases |