Bioequivalence Study of SAL001 and FORSTEO in Healthy Chinese Adults

Postmenopausal Osteoporosis Clinical Trial

Official title:

A Randomized, Open, Self-crossover, Single-dose Clinical Study to Compare Pharmacokinetic of Teriparatide Injection (SAL001) and the Original Drug FORSTEO in Healthy Chinese Adult Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04747392
• Other study ID #: SAL001A101
• Status: Completed
• Phase: Phase 1
• Start date: August 19, 2020
• Est. completion date: November 11, 2020

Study information

• Verified date: February 2021
• Source: Shenzhen Salubris Pharmaceuticals Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single-center, randomized, open label, single-dose, the original drug controlled, crossover design, two sequence, two periods, Phase Ⅰclinical study. 64 qualified subjects will be randomly assigned to two administration sequences (sequence A and sequence B) at the ratio of 1∶1, with 32 subjects in each sequence. Each period will be given subcutaneous injection once, and the washout period will be 72 hours, and each subject will be given subcutaneous injection twice. Sequence A: the test drug (SAL001) is injected in the first period, and the reference drug (FORSTEO) is injected in the second period. Sequence B: the reference drug (FORSTEO) is injected in the first period, and the test drug (SAL001) is injected in the second period. If the geometric mean ratio (GMR) 90% confidence interval of the major pharmacokinetic indexes (AUC0-t, Cmax) for SAL001 and FORSTEO is between 80.00% and 125.00%, the two drugs are considered to be bioequivalent.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: November 11, 2020
• Est. primary completion date: October 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 50 Years

Eligibility

Inclusion Criteria:

1. Those who volunteer to participate in the trial and sign the informed consent form.

2. Healthy Chinese male or female adults, the number of single sex volunteers is no less than 1/3, aged 20 to 50 years old (including the boundary value).

3. Males weighted =50kg, females weighted =45kg, body mass index (BMI) between 19-25 kg/m^2 (including boundary value), BMI= weight (kg)/height^2 (m^2).

Exclusion Criteria:

1. The existence of clinically significant diseases of heart, liver, lung, kidney, digestive tract, endocrine, metabolic and hematological systems.

2. history of parathyroid disease, or abnormal PTH with clinically significance judged by investigators.

3. Physical examination, laboratory examination, electrocardiogram (ECG), chest radiograph, abdominal ultrasound san(digestive system, urinary system), vital signs, etc., indicate that the subject has clinically significant abnormalities judged by the investigator.

4. Serum total calcium > upper limit of normal according to the normal range of the center, or previous hypercalcemia.

5. Hyperuricemia, or a previous history of gout, or abnormal blood uric acid with clinically significance judged by investigators at the time of screening.

6. Those with active urolithiasis.

7. Those who had received anti-osteoporosis agents (such as bisphosphonates, calcitonin, estrogen, selective estrogen receptor modulator, parathyroid hormone and its analogues, strontium salts, active vitamin D and its analogues, vitamin K2, etc.) within 6 months before the first administration of the trial.

8. Those who had received oral or intravenous administration of glucocorticoids 3 months before the first administration of the trial.

9. Those who had taken any drug within 14 days before the first administration of the trial.

10. Allergies, such as allergic to two or more kinds of drugs or food; or known allergic to this drug components.

11. Alcoholism within 1 year before screening (drinking more than 3 times a day or more than 7 times a week, drinking 1 time =150mL red wine, or 360mL beer, or 50mL white wine), or a positive alcohol breath test.

12. A history of drug abuse within 1 year before screening, or a positive urine test for drugs at screening.

13. Those who were smoking more than 5 cigarettes a day within 3 months before screening.

14. Those who had participated in any other clinical trial within 3 months before the first administration of the trial.

15. Those who had blood donation or blood loss =400mL within 3 months before the first administration of the trial.

16. Those who do not agree to avoid the use of tobacco, alcohol or caffeinated beverages within 24 hours before the administration and during the trial, or do not agree to avoid strenuous exercise, or do not agree to avoid other factors affecting the absorption, distribution, metabolism and excretion of the drug.

17. Women who are pregnant or lactating, or who are positive for serum HCG, or who cannot/do not follow the instructions of investigators to take contraceptive measures approved by investigators during the study period.

18. Those who intend to give birth within 1 year.

19. Those with positive results of HBV surface antigen, or hepatitis C virus antibody positive, or Treponema pallidum antibody positive, or human immunodeficiency virus antibody positive.

20. Those with positive results of novel coronavirus nucleic acid test.

21. Those who are considered to be unsuitable for participation in this clinical study by investigators.

Related Conditions & MeSH terms

• Osteoporosis
• Osteoporosis, Postmenopausal
• Postmenopausal Osteoporosis

Intervention

Biological:
• SAL001
administrated once by subcutaneous injection
• FORSTEO
administrated once by subcutaneous injection

Locations

Country	Name	City	State
China	The Fifth Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Shenzhen Salubris Pharmaceuticals Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PK parameters: area under the plasma concentration time curve from-time zero to time t (AUC0-t)	Central lab will be used to detect the plasma concentration of drugs.	Within 60 minutes before administration, and 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 210, 240, and 300 minutes after administration of Day 1 and Day 4
Primary	PK parameters: peak plasma concentration (Cmax)	Central lab will be used to detect the plasma concentration of drugs.	Within 60 minutes before administration, and 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 210, 240, and 300 minutes after administration of Day 1 and Day 4
Secondary	PK parameters: area under the plasma concentration time curve from time zero to time infinity (AUC0-8)	Central lab will be used to detect the plasma concentration of drugs.	Within 60 minutes before administration, and 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 210, 240, and 300 minutes after administration of Day 1 and Day 4
Secondary	PK parameters: time to reach peak drug concentration (Tmax)	Central lab will be used to detect the plasma concentration of drugs.	Within 60 minutes before administration, and 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 210, 240, and 300 minutes after administration of Day 1 and Day 4
Secondary	PK parameters: half-life (t1/2)	Central lab will be used to detect the plasma concentration of drugs.	Within 60 minutes before administration, and 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 210, 240, and 300 minutes after administration of Day 1 and Day 4
Secondary	PK parameters: AUC extrapolated from Tmax to infinity in percentage of the total AUC (AUC%extrap)	Central lab will be used to detect the plasma concentration of drugs.	Within 60 minutes before administration, and 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 210, 240, and 300 minutes after administration of Day 1 and Day 4
Secondary	PK parameters: time to last measurable concentration (Tlast)	Central lab will be used to detect the plasma concentration of drugs.	Within 60 minutes before administration, and 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 210, 240, and 300 minutes after administration of Day 1 and Day 4
Secondary	PK parameters: terminal elimination rate constant (?z)	Central lab will be used to detect the plasma concentration of drugs.	Within 60 minutes before administration, and 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 210, 240, and 300 minutes after administration of Day 1 and Day 4
Secondary	PK parameters: apparent total clearance (CL/F)	Central lab will be used to detect the plasma concentration of drugs.	Within 60 minutes before administration, and 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 210, 240, and 300 minutes after administration of Day 1 and Day 4
Secondary	PK parameters: apparent distribution volume (Vz/F)	Central lab will be used to detect the plasma concentration of drugs.	Within 60 minutes before administration, and 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 210, 240, and 300 minutes after administration of Day 1 and Day 4
Secondary	PK parameters: mean residence time from time zero to t (MRT0-t)	Central lab will be used to detect the plasma concentration of drugs.	Within 60 minutes before administration, and 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 210, 240, and 300 minutes after administration of Day 1 and Day 4
Secondary	PK parameters: mean residence time from time zero to infinity (MRT0-8)	Central lab will be used to detect the plasma concentration of drugs.	Within 60 minutes before administration, and 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 210, 240, and 300 minutes after administration of Day 1 and Day 4
Secondary	PD parameters: area under the serum concentration time curve from-time zero to time t (AUC0-t)	Central lab will be used to detect the serum total calcium concentration. Serum-corrected calcium concentration will be use to calculate above PD parameters.	Within 60 minutes before administration, and 120, 180, 240, 360, 480, 720 minutes after administration of Day 1 and Day 4
Secondary	PD parameters: area under the serum concentration time curve from time zero to time infinity (AUC0-8)	Central lab will be used to detect the serum total calcium concentration. Serum-corrected calcium concentration will be use to calculate above PD parameters.	Within 60 minutes before administration, and 120, 180, 240, 360, 480, 720 minutes after administration of Day 1 and Day 4
Secondary	PD parameters: peak serum concentration (Cmax)	Central lab will be used to detect the serum total calcium concentration. Serum-corrected calcium concentration will be use to calculate above PD parameters.	Within 60 minutes before administration, and 120, 180, 240, 360, 480, 720 minutes after administration of Day 1 and Day 4
Secondary	PD parameters: time to reach peak serum concentration (Tmax)	Central lab will be used to detect the serum total calcium concentration. Serum-corrected calcium concentration will be use to calculate above PD parameters.	Within 60 minutes before administration, and 120, 180, 240, 360, 480, 720 minutes after administration of Day 1 and Day 4