A Trial of SHR6508 in Secondary Hyperparathyroidism

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

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

Study Overview

• Status: Completed
• Conditions: Secondary Hyperparathyroidism
• Intervention / Treatment: Drug: SHR6508；Placebo; Drug: SHR6508；Placebo; Drug: SHR6508；Placebo; Drug: SHR6508；Placebo

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Guangdong Provincial People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Able and willing to provide a written informed consent
2. Diagnosed with end stage renal disease receiving stable hemodialysis
3. Male or female
4. Meet the Body Mass Index standard
5. Conform to the ASA Physical Status Classification
6. Stably use of concomitant medication of other therapies of SHPT
7. Meet the standard of iPTH level, cCa and HB

Exclusion Criteria:

1. Subjects with a history of malignant tumor
2. Subjects with neuropsychiatric diseases
3. Subjects with a history of cardiovascular diseases
4. Subjects with gastrointestinal diseases
5. Subjects with a history of surgery
6. Subjects with a history of blood loss
7. Subjects with a history of parathyroidectomy or planned during the study
8. Subjects with a history of kidney transplant or planned during the study
9. Abnormal blood pressure, serum magnesium, serum transaminase, serum albumin, platelet counts.
10. Subjects with a treatment history of similar drugs
11. Allergic to a drug ingredient or component
12. Pregnant or nursing women
13. No birth control during the specified period of time
14. Subject with a history of alcohol abuse and drug abuse
15. Participated in clinical trials of other drugs (received experimental drugs)
16. The investigators determined that other conditions were inappropriate for participation in this clinical trial

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2022
• Primary Completion (Actual): July 7, 2023
• Study Completion (Actual): August 2, 2023

Study Registration Dates

• First Submitted: January 7, 2022
• First Submitted That Met QC Criteria: January 20, 2022
• First Posted (Actual): February 2, 2022

Study Record Updates

• Last Update Posted (Actual): August 8, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Parathyroid Diseases; Neoplastic Processes; Hyperparathyroidism; Neoplasm Metastasis; Hyperparathyroidism, Secondary
• Other Study ID Numbers: SHR6508-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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