the pk/pd study of a single subcutaneous injection of shr-1222 in healthy subjects

Conditions: Osteoporosis

Summary: this is a single center, randomized, double-blind, dose escalation, placebo parallel controlled phaseⅰclinical study to evaluate the safety, tolerability and pharmacokinetics, pharmacodynamics with a single subcutaneous injection of shr-1222 in healthy subjects. the primary objective of this study is to investigate the safety and tolerability of a range of subcutaneous shr-1222 in healthy subjects. secondary objectives are to determine the pharmacokinetics (pk) and pharmacodynamics(pd) profile of shr-1222 in healthy subjects including assessment of immunogenicity.

50 adult healthy subjects with 5 dose groups will be enrolled in the study, including six subjects in the lowest dose group, four of whom received the shr-1209 and two of whom received the placebo. the other three groups have 11 subjects in each group, 9 administered shr-1222 and 2 administered placebo. the primary endpoint is the safety and tolerability : adverse events, vital signs, physical examination, laboratory examination, 12 lead electrocardiogram, injection site reactions, etc.

Eligibility criteria:
inclusion criteria: * signed informed consent; * male or postmenopausal female; * age ≥45 and ≤59 years old; * the body mass index (bmi) ≥18.5kg/m2 and ≤28 kg/m2; * t value of areal bone mineral density on any lumbar spine (l1-l4) or collum femoris\>-2.5 and \<-1; * the comprehensive physical examination is eligible or slightly abnormal but the researchers determine no clinical implication; * no smoking, alcohol or drugs abuse. exclusion criteria: * any disease affecting bone metabolism; * past medical history of cerebral infarction or cerebral arterial thrombosis; * past medical history of myocardial infarction; * administration of the following drugs within 6m: hormone replacement therapy, calcitonin parathyroid hormone (or any derivative), supplemental vitamin d\>1,000 iu/day, glucocorticosteroids (inhaled or topical corticosteroids administered more than 2 weeks before the enrollment date are allowed), anabolic steroids, calcitriol and available analogues, thiazide diuretics; * administration of the following drugs within 12m: bisphosphonates, fluoride for osteoporosis; * a bone fracture within the previous 6 months; * a lumbar spine l1-l4 or femoral neck t-score ≤-2.5; * alanine aminotransferase (alt) or aspartate aminotransferase (ast) or gamma pancreatic acyl transferase (ggt) or total bilirubin, more than 1.5 x uln during screening; * 3 months prior to screening involved in any drug clinical subjects; * subjects determined by the researchers have any food, dietary supplement or drugs that affect shr-1222 absorption, distribution, metabolism and excretion in 4 weeks prior to screening or within 5 half-lives; * serious infection, trauma or major surgery in 4 weeks prior to screening; * a surgery plan during the study; * blood donation and transfusion in 3 months prior to screening; * unstable thyroid dysfunction in 6 months prior to screening; * human immunodeficiency virus antibody (hiv-ab), syphilis serological examination, hepatitis b virus surface antigen (hbsag), hepatitis c virus antibody (hcv-ab) were positive; * intolerant to venous blood collection; * a clinical history of drug allergy or a history of atopic allergic diseases (asthma, urticaria, eczema dermatitis) or a known allergy to experimental or similar * subjects with any other situation should not be involved, which determined by the researchers.