A study of Denosumab in patients.
- Conditions
- Health Condition 1: M810- Age-related osteoporosis without current pathological fracture
- Registration Number
- CTRI/2021/09/036190
- Lead Sponsor
- Intas Pharmaceutical Limited Biopharma Division
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Yet Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
1.Participant must sign an ICF to participate in the study indicating that she understands the purpose of, and procedures required for the study as described in this protocol and is willing to and will be able to adhere to requirement of the protocol.
2.Participant must be 55 to 90 years of age (both inclusive), at the time of signing the informed consent.
3.Participants who are medically/clinically stable on the basis of physical examination, medical history, vital signs, chest x-ray PA view, 12-lead ECG and clinical laboratory parameters performed at screening. Any abnormalities or deviation from normal, must be consistent with the underlying illness in the study population and judged by investigator to be not clinically significant. This determination must be recorded in the participants source documents and initialed by the investigator.
4.Participants whose absolute bone mineral density T-score is less than equal to -2.5 and greater than equal -4.0 at the lumbar spine as measured by DXA (dual-energy x-ray absorptiometry), confirmed by the independent central imaging team
5.At least two vertebrae in the L1-L4 region and at least one hip joint are evaluable by DXA, confirmed by the independent central imaging team
6.Body weight between 50 kg and 90 kg (both inclusive) at screening.
7.Postmenopausal ambulatory female and not considered to be of child-bearing potential if:
a.Women are considered post-menopausal and not of child-bearing potential if,
i.They have had 12 months of natural (spontaneous) amenorrhea (no vaginal bleeding or spotting) with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) OR
ii.Six months of spontaneous amenorrhea with serum FSH levels greater than 40 mIU per mL OR
iii.Have had surgical bilateral oophorectomy (with or without hysterectomy) at least six months ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment if she is considered not of child-bearing potential.
1.Documented medical history of clinically significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
2.Documented medical history of known allergies, hypersensitivity, or intolerance to denosumab or its excipients (refer to the IB)
3.History of any prior use of denosumab
4.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
5.Documented medical history of latex or dry natural rubber allergy
6.Contraindications to the use of denosumab or Vitamin D and Calcium as per IB/local prescribing information at screening and/or baseline
7.Documented medical history and/or current evidence of any of the following oral/dental conditions
a.Prior history or current evidence of osteomyelitis or osteonecrosis of the jaw.
b.Active dental or jaw condition which requires oral surgery.
c.Planned invasive dental procedure expected during study period.
d.Current evidence non-healed dental or oral surgery.
e.Current evidence of poor oral hygiene
f.Ill-fitting denture
8.Current hyper- or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range at screening. Serum calcium levels may be retested once in case of an elevated/low serum calcium level as assessed by the clinical laboratory. Final decision to include the patient based on the risk of hypocalcemia to be taken by the Investigator.
9.History of frequent occurrence of hypocalcemia, history of severe hypocalcemia or presence of diseases that can precipitate hypocalcemia frequently (like malabsorption syndromes (for example celiac disease, history of excision of small intestine etc.) and severe renal impairment)
10.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
11.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.
12.25 (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.
13.History of external beam or implant radiation therapy involving the skeleton.
14.History and /or presence of 1 severe fracture or 2 moderate vertebral fractures
15.Patients with bone metastases or a history of malignancies affecting bones.
16.Smokers or who have smoked within last 06 months prior to start of the study.
17.Documented medical history of major surgery, (e.g. requiring general anesthesia) within 12 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study.
Note: Participants with planned surgical procedures to be conducted under local anesthesia may participate.
18.Documented medical history of hepatitis B surface anti
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method - To compare the pharmacokinetic parameters of denosumab and denosumab-ref in postmenopausal women with osteoporosis. <br/ ><br>- To compare the pharmacodynamic effect of treatment with denosumab and denosumab-ref on bone mineral density (BMD) and bone resorption marker in postmenopausal women with osteoporosisTimepoint: - Pharmacokinetics: Cmax, AUC0-t, and AUC0-infinity after first dose of denosumab and denosumab-ref <br/ ><br>- Mean percentage change in BMD at lumbar spine from baseline to 12 months between denosumab and denosumab-ref <br/ ><br>- Pharmacodynamics: Emax and AUEC0-t of % reduction from baseline serum C-terminal telopeptide (CTX) after first dose of denosumab and denosumab-ref
- Secondary Outcome Measures
Name Time Method To compare the efficacy of treatment with denosumab and denosumab-ref in postmenopausal women with osteoporosisTimepoint: Incidence of clinical fracture between denosumab and denosumab-ref over 12 months.;To compare the immunogenicity of denosumab and denosumab-ref in postmenopausal women with osteoporosisTimepoint: Incidence of anti-denosumab antibody in denosumab and denosumab-ref arm over 12 months;To compare the pharmacodynamic effects of the treatment with denosumab and denosumab-ref in postmenopausal women with osteoporosisTimepoint: Mean percentage change in bone mineral density (BMD) of lumbar spine from baseline to 06 months between denosumab and denosumab-ref