A Trial of SHR6508 in Secondary Hyperparathyroidism

Study Overview
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Brief Summary
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The study is being conducted to evaluate the tolerability, pharmacokinetics and pharmacodynamics of SHR6508 for Chinese patients with secondary hyperparathyroidism of chronic kidney disease treated by maintenance hemodialysis

Official Title
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Study on Tolerability, Pharmacokinetics and Pharmacodynamics of SHR6508 in Chinese Patients With Secondary Hyperparathyroidism of Chronic Kidney Disease Treated by Maintenance Hemodialysis

Conditions
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Secondary Hyperparathyroidism

Intervention / Treatment
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* Drug: SHR6508；Placebo
* Drug: SHR6508；Placebo
* Drug: SHR6508；Placebo
* Drug: SHR6508；Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to provide a written informed consent Diagnosed with end stage renal disease receiving stable hemodialysis Male or female Meet the Body Mass Index standard Conform to the ASA Physical Status Classification Stably use of concomitant medication of other therapies of SHPT Meet the standard of iPTH level, cCa and HB Exclusion Criteria: Subjects with a history of malignant tumor Subjects with neuropsychiatric diseases Subjects with a history of cardiovascular diseases Subjects with gastrointestinal diseases Subjects with a history of surgery Subjects with a history of blood loss Subjects with a history of parathyroidectomy or planned during the study Subjects with a history of kidney transplant or planned during the study Abnormal blood pressure, serum magnesium, serum transaminase, serum albumin, platelet counts. Subjects with a treatment history of similar drugs Allergic to a drug ingredient or component Pregnant or nursing women No birth control during the specified period of time Subject with a history of alcohol abuse and drug abuse Participated in clinical trials of other drugs (received experimental drugs) The investigators determined that other conditions were inappropriate for participation in this clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: SHR6508 compared with placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group A<br>Experimental: SHR6508 Placebo Comparator: normal saline | Drug: SHR6508；Placebo<br>* Group A:SHR6508 low dose<br>|
| Experimental: group B<br>Experimental: SHR6508 Placebo Comparator: normal saline | Drug: SHR6508；Placebo<br>* Group B:SHR6508 medium dose<br>|
| Experimental: group C<br>Experimental: SHR6508 Placebo Comparator: normal saline | Drug: SHR6508；Placebo<br>* Group C:SHR6508 high dose<br>|
| Experimental: group D<br>Experimental: SHR6508 Placebo Comparator: normal saline | Drug: SHR6508；Placebo<br>* Group D:SHR6508 high dose(single dose)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax, Time of maximum observed concentration. |  | 0 hour to 43 hours after first dose administration | 
| Cmax, Maximum observed concentration. |  | 0 hour to 43 hours after first dose administration | 
| AUC0-t, Area under the concentration-time curve from time zero to the last measurable concentration. |  | 0 hour to 43 hours after first dose administration | 
| AUC0-∞, Area under the curve from time 0 extrapolated to infinite time |  | 0 hour to 43 hours after first dose administration | 
| t1/2z, Terminal elimination half-life |  | 0 hour to 43 hours after first dose administration | 
| CLz, Total Body Clearance |  | 0 hour to 43 hours after first dose administration | 
| Vz, Volume of distribution based on the terminal phase |  | 0 hour to 43 hours after first dose administration | 
| MRT0-t, Mean residence time from time zero to the last measurable concentration. |  | 0 hour to 43 hours after first dose administration | 
| MRT0-∞, Mean residence time from time 0 extrapolated to infinite time |  | 0 hour to 43 hours after first dose administration | 
| Cmax,ss : Maximum observed concentration at steady-state. |  | Day1-Day29(if reach steady-state) | 
| Cmin,ss : Minimum observed concentration at steady-state |  | Day1-Day29(if reach steady-state) | 
| Cav : Average concentration |  | Day1-Day29(if reach steady-state) | 
| AUC0-t,ss, Area under the concentration-time curve from time zero to the last measurable concentration at steady-state. |  | Day1-Day29(if reach steady-state) | 
| AUC0-∞,ss, Area under the concentration-time curve from time 0 extrapolated to infinite time at steady-state. |  | Day1-Day29(if reach steady-state) | 
| Tmax,ss, Time of maximum observed concentration at steady-state. |  | Day1-Day29(if reach steady-state) | 
| t1/2z,ss, Terminal elimination half-life at steady-state |  | Day1-Day29(if reach steady-state) | 
| CLss, Total Body Clearance at steady-state. |  | Day1-Day29(if reach steady-state) | 
| Vss, Volume of distribution based on the terminal phase at steady-state. |  | Day1-Day29(if reach steady-state) | 
| MRT0-∞, Mean residence time from time 0 extrapolated to infinite time. |  | Day1-Day29(if reach steady-state) | 
| DF: Degree of Fluctuation |  | Day1-Day29(if reach steady-state) | 
| Accumulation Ratio |  | Day1-Day29(if reach steady-state) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in serum iPTH, cCa, P, FGF23 and BSAP | iPTH, FGF23 and BSAP were tested at a central laboratory. | 0 hour to 43 hours after first dose administration | 
| Change From Baseline to End of Study in serum iPTH, cCa, P, FGF23 and BSAP | iPTH, FGF23 and BSAP were tested at a central laboratory. | Day1 to Day29 | 
| Proportion of Participants to End of Study whose iPTH decreased by≥30% from baseline | iPTH was tested at a central laboratory. | Day1 to Day29 | 
| Proportion of Participants to End of Study whose iPTH decreased to 300 pg/mL from baseline | iPTH was tested at a central laboratory | Day1 to Day29 | 
| Participants With Treatment-Emergent Adverse Events (TEAEs) | Terms were coded with Medical Dictionary for Regulatory Activities (MedDRA) | Day1 to End of Study, End of Study is about Day55 |