A Randomized,Double Blind,Active Controlled Parallel Arm Multicenter Study Comparing Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Denosumab of Intas Pharmaceutical Limited (60 mg/mL) With Prolia® in Postmenopausal Women With Osteoporosis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 552
- 试验地点
- 1
- 主要终点
- Area under the concentration versus time curve from time zero to infinity. Where AUC 0-∞= AUC0-t + Ct2, Ct is the last measurable concentration and t2 is the terminal rate constant
研究概览
简要总结
Denosumab of Intas is biosimilar denosumab candidate under development by Intas Pharmaceutical Limited (Biopharma Division). Denosumab of Intas is already approved by Indian drug licensing authority- Drug Controller General (India) for marketing in Indian population since 2018.As per regulatory requirement, a comparative clinical study to establish Pharmacokinetic, Pharmacodynamic and Immunogenicity equivalence is required to conclude therapeutic equivalence to obtain marketing authorization of a biosimilar investigational product. This is a multicenter, randomized, double-blind, active controlled study in approximately 552postmenopausal women with osteoporosis.
An extension of the study is planned after completion of the initial 1 year of treatment. This extension is with the objective of submitting data on safety, and Immunogenicity, after switching of Prolia treatment arm to either Prolia or Intas denosumab for 6 months. This switching data is applicable only for FDA submission. Only patients who have undergone PK assessment will be eligible for the extension phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
double-blinded. Participant, Investigator and Outcomes Assessor are masked
入排标准
- 年龄范围
- 55 Years 至 90 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Documented medical history of clinically significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
- •Documented medical history of known allergies, hypersensitivity, or intolerance to denosumab or its excipients (refer to the IB)
- •Documented medical history of metabolic or bone disease (except osteoporosis) that may interfere with the interpretation of the results, such as Pagets disease, osteomalacia, osteogenesis imperfecta, osteopetrosis, rheumatoid arthritis, ankylosing spondylitis or any other joint disease limiting mobility, Cushings disease, hyperprolactinemia, malabsorption syndrome
- •Contraindications to the use of denosumab or Vitamin D and Calcium as per IB/local prescribing information at screening and/or baseline
- •Documented medical history and/or current evidence of any of the following oral/dental conditions
- •Prior history or current evidence of osteomyelitis or osteonecrosis of the jaw.
- •Active dental or jaw condition which requires oral surgery.
- •Planned invasive dental procedure expected during study period.
- •Current evidence non-healed dental or oral surgery.
- •Current evidence of poor oral hygiene
- •Ill-fitting denture
- •Current hyper- or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range at screening.
- •Current, uncontrolled hyper- or hypoparathyroidism and history of hypoparathyroidism, per participant report or chart review. PTH outside the normal range (15-65 pg/mL) as assessed by central laboratory
- •Current, uncontrolled hyper- or hypothyroidism, defined as thyroid stimulating hormone outside of the normal range (TSH-0.465 to 4.68 mIU/L) at screening.
- •25 (OH) Vitamin D lower than 20 ng/mL as assessed by the central laboratory at Screening. Vitamin D repletion will be permitted, and participants may be rescreened once.
- •History and /or presence of 1 severe fracture or 2 moderate vertebral fractures
- •Smokers or who have smoked within last 06 months prior to start of the study.
- •Administration of bisphosphonate as follows: - c. IV Bisphosphonate in the past 3 years d. Oral bisphosphonates treatment for osteoporosis i. More than 3 years of cumulative use ii. Any dose received within 6 months prior to randomization iii. More than 1 month of cumulative use between 6 and 12 months prior to randomization
- •Teriparatide or any PTH analogs treatment received within 12 months prior to randomization.
- •Systemic oral or transdermal estrogen, SERMs, or calcitonin treatment of more than 1 month of cumulative use within 6 months prior to randomization.
- •Androgen deprivation or hormonal ablation therapy of more than 1 month of cumulative use within 6 months prior to randomization.
- •Tibolone or cinacalcet treatment received within 3 months prior to randomization
- •Systemic glucocorticoids: Greater than equal to 5 mg prednisone equivalent per day for more than 10 days within 3 months prior to randomization.
研究组 & 干预措施
Denosumab Solution for injection in single use prefilled syringe 60 mg permL
Unit Dose Strength 60 mg per mL,Dosage Level 60 mg once every 6 months, Route of Administration-Subcutaneous injection
干预措施: Denosumab (Drug)
Prolia® Solution for injection in single use prefilled syringe 60 mg per mL
Unit Dose Strength 60 mg per mL,Dosage Level 60 mg once every 6 months,Route of Administration-Subcutaneous injection
干预措施: Denosumab-Ref (Drug)
结局指标
主要结局
Area under the concentration versus time curve from time zero to infinity. Where AUC 0-∞= AUC0-t + Ct2, Ct is the last measurable concentration and t2 is the terminal rate constant
时间窗: Day 1 to Day 181
Maximum measured concentration after first dose of denosumab and denosumab-ref., ,
时间窗: Day 1 to Day 181
Area under the concentration versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method between denosumab and denosumab-ref postmenopausal women with osteoporosis
时间窗: Day 1 to Day 181
次要结局
- Maximum percent reduction from baseline Emax percent reduction from baseline serum C-terminal telopeptide (CTX) after first dose of denosumab and denosumab-ref*(Day 1 to Day 181)
- Area under the percent reduction from baseline versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method(Day 1 to Day 181)