A Study to Evaluate LY06006 and Prolia in Healthy Adults

Study Overview
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Brief Summary
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A randomized, double-blind, parallel-group study in Chinese healthy male subjects to evaluate the pharmacokinetics, pharmacodynamics, safety and immunogenicity of LY06006 versus Prolia following single-dose subcutaneous injection

Detailed Description
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Study Design: The study is a randomized, double-blind, parallel-group study in healthy adult male subjects to evaluate the pharmacokinetics, pharmacodynamics, safety and immunogenicity of LY06006 versus Prolia following single-dose subcutaneous injection. A total of 168 healthy male subjects will be randomized 1:1 to receive a single subcutaneous (s.c.) injection of 60mg of either LY06006 ( LY06006 , 60 mg/1mL , Shandong Luye Pharmaceutical Co., Ltd.) or Prolia (60 mg / 1 mL , Amgen Inc.). During the entire study period, blood samples should be collected according to the Schedule of Assessments for pharmacokinetic, pharmacodynamic and immunogenicity analysis, and safety assessments should be conducted.

Official Title
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A Randomized, Double-blind, Parallel-group Study in Chinese Healthy Male Subjects to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of LY06006 Versus Prolia Following Single-dose Subcutaneous Injection

Conditions
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Healthy Adults

Intervention / Treatment
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* Drug: LY06006
* Drug: Prolia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily signed the informed consent form; Healthy males，ages ≥18 to ≤50 years; Body weight ≥58 to ≤68 kg and Body mass index (BMI) >18 to <28 kg/m2, body mass index (BMI) = weight ( kg ) / height 2 (m 2); Normal or clinically acceptable vital signs, physical exams, laboratory tests, 12- lead ECG, abdominal color Doppler ultrasound, chest radiograph, etc. screening; No pregnancy plans and voluntarily take effective contraceptive measures from the screening date to the end of the study . Exclusion Criteria: Prior diagnosis of bone disease, or any condition that will affect bone metabolism such as, but not limit to: malignant tumors ( including myeloma ), hypoparathyroidism / hyperthyroidism, hypothyroidism / hyperthyroidism, acromegaly, Cushing ' s syndrome, hypopituitarism, severe chronic obstructive pulmonary disease, rheumatoid arthritis, osteomalacia; Prior history or current evidence of osteomyelitis or osteonecrosis of the jaw (ONJ), or risk factors for ONJ such as invasive dental surgery or jaw surgery during the trial, or unhealed dental or oral surgery wounds; Recent bone fracture within 6 months; Active and unhealed infections of the respiratory system, digestive system, urinary system, reproductive system, or skin; Serum calcium of < Lower Limit of Normal (LLN) or > Upper Limit of Normal (ULN); Prior use of medications affecting bone turnover before screening and for the duration of study, including but not limited to: denosumab, bisphosphonates or fluoride within 12 months, contraceptives containing estrogen, tibolone, estrogen, selective estrogen receptor modulators, aromatase inhibitors, calcitonin, strontium salts, parathyroid hormone (or derivatives), vitamin D supplements ( >1000 IU/ day), anabolic steroids, systemic glucocorticoids, calcitriol or similar, diuretics, anticonvulsants within 6 months; inhaled or topical glucocorticoid drugs within 2 weeks; Allergy to more than two drugs or food, or allergy to the ingredients of the investigational medicinal product (IMP); Blood donation or massive blood loss ( ≥200 mL ) within 3 months before screening ; Any vaccination within 6 months before screening or for the duration of study; Prior use of any prescription drugs, over-the-counter drugs, any vitamin products or herbal medicines within 14 days before screening ; Intense physical exercise within 2 weeks before screening or for the duration of the study, or any other conditions affecting drug absorption, distribution, metabolism, and excretion; Upon enquiry, prior smoke more than 5 cigarettes per day within 3 months before the study; Upon enquiry, a history of alcohol abuse ( drinking more than 14 units of alcohol per week within the first three months prior to screening : 1 unit = 350 mL of beer, 45 mL of liquor, or 150 mL of wine ), or positive alcohol test; Positive urine screen for drug or a history of drug abuse or drug use in the past five years upon questioning ; Other diseases with clinical significance (such as nervous system, mental system , cardiovascular system, urinary system, digestive system, respiratory system, metabolic endocrine system, blood system, skin disease, immune disease, tumor, etc.); Any of the following tests positive: hepatitis B surface antigen ( HBsAg ), hepatitis C antibody ( HCV-AB ), human immunodeficiency virus antigen antibody ( HIVAg / Ab ) and treponema pallidum antibody; Acute diseases or concomitant medications from screening to IMP administration; Consumption of any alcohol-containing products within 48 hours before administration of the IMP ; Prior participation in clinical trials for denosumab or denosumab biosimilar products; current participation in other clinical studies, or receiving or have received any investigational drug within 3 months (or less than 5-half lives of that medication, whichever time period is longer) before receiving study drug ; History of fainting blood or needles; In the opinion of the investigator, others to be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY06006<br>60 mg/1 ml, once every 6 months administered subcutaneously | Drug: LY06006<br>* 60 mg/1 ml, once every 6 months administered subcutaneously<br>* Other names: subcutaneous injection of 60 mg;|
| Active Comparator: Prolia<br>60 mg/1 ml, once every 6 months administered subcutaneously | Drug: Prolia<br>* 60 mg/1 ml, once every 6 months administered subcutaneously<br>* Other names: Denosumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC 0- ∞ | Area under the concentration-time curve from time zero to infinity | 168 days | 
| C max | Maximum observed concentration | 168 days | 
| s-CTX | Percent change in serum s-CTX from baseline. | 168 days | 
| AUEC0-t | The pharmacodynamic parameters | 168 days | 
| Emax | The pharmacodynamic parameters | 168 days | 
| TEmax | The pharmacodynamic parameters | 168 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vital signs：Temperature | Safety measures | 168 days | 
| Vital signs：pulse | Safety measures | 168 days | 
| Vital signs： blood pressure | Safety measures | 168 days | 
| Vital signs： respiration | Safety measures | 168 days | 
| Physical examination：general | Safety measures | 168 days | 
| Physical examination：head and neck region | Safety measures | 168 days | 
| Physical examination：lymph gland | Safety measures | 168 days | 
| Physical examination： oral cavity | Safety measures | 168 days | 
| Physical examination：chest | Safety measures | 168 days | 
| Physical examination：belly | Safety measures | 168 days | 
| Physical examination：Extremities and spine | Safety measures | 168 days | 
| Physical examination：nervous system | Safety measures | 168 days | 
| Laboratory tests：hematology | Safety measures | 168 days | 
| Laboratory tests：chemistry | Safety measures | 168 days | 
| Laboratory tests：urinalysis | Safety measures | 168 days | 
| Laboratory tests：parathyroid hormone | Safety measures | 168 days | 
| Laboratory tests：thyroid function | Safety measures | 168 days | 
| Laboratory tests：abdomen ultrasound | Safety measures | 168 days | 
| Laboratory tests：chest radiography | Safety measures | 168 days | 
| Laboratory tests：coagulation function | Safety measures | 168 days | 
| Electrocardiogram (12-Lead ECG) | Safety measures | 168 days | 
| Adverse events(AEs) | Safety measures | 168 days | 
| ADA | The incidence and antibody titer of ADA | 168 days | 
| Nab | The incidence of Nab. | 168 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Compare, Pharmacokinetics, Pharmacodynamics, Safety, Immunogenicity, LY06006, Prolia, Healthy Adults