BIOEQUIVALENCE STUDY OF THREE PRODUCTS OF DENOSUMAB (120 MG/1.7 ML) IN HEALTHY ADULT HUMAN MALE SUBJECTS
- Registration Number
- CTRI/2020/09/027619
- Lead Sponsor
- Intas Pharmaceuticals Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Yet Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
1. Normal, healthy, adult, human male subjects greater than equal to 28 to less than equal to 55 years of age (both inclusive)
2. Having a Body Mass Index (BMI) between 18.5 to 30 (both inclusive) kg / m2 and
weighing > 50 kg and less than 90 kg.
3. Able to comply with the study procedures, as per the opinion of the Principal Investigator.
4. Able to give voluntary written informed consent for participation in the trial.
5. Not having any significant disease or abnormal findings during screening, medical
history, clinical examination, vital sign examination (Pulse rate, blood pressure,
Respiratory rate and temperature), laboratory evaluations, 12- lead ECG and X-ray chest
(P/A view).
1.History of hypersensitivity or idiosyncratic reaction to Denosumab or its excipients or prior use of denosumab or other Chinese Hamster Ovary cell line derived products or to drugs of similar chemical classes or any related drug.
2.Subjects with known latex allergies.
3.Subjects will be assessed for postural hypotension (Defined as decrease in systolic blood pressure of 20 mm Hg or a decrease in diastolic blood pressure of 10 mm Hg and increase in heart rate (greater than 20 bpm) (compared to the sitting results) within 3 minutes of standing when compared with blood pressure from sitting position) and confirmed unsafe for study inclusion by the investigator.
4.History or presence of any disease or disorder known to influence bone metabolism including history of non-traumatic fractures except Vitamin D deficiency requiring replacement.
5.History or presence of any disease or disorder known to compromise the haemopoietic, renal, hepatic, endocrine, pulmonary, central nervous, cardiovascular, immunological, dermatological, gastrointestinal or any other body system.
6.Any clinically significant ECG abnormalities at Screening.
7.Any evidence of tuberculosis as per X-ray chest (P/A view) recordings.
8.History of malignancy of any organ system treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
9.Fertile males, defined as all males physiologically capable of conceiving offspring UNLESS the subject agrees to comply with two highly effective contraceptive methods comprising a barrier method (condom or occlusive cap plus spermicide) for the entire duration of the study, up to end of the study (after last ambulatory sample),.
10.Smokers or tobacco users, who consumed tobacco or tobacco-containing products (gutkha, pan/pan masala, beedi, cigarettes, others) within 6 months prior to start of the study or has inability to abstain from smoking during the study period.
11.Subjects with history of ingestion of any prescription drugs, herbal supplements within 4 weeks prior to initial dosing and/or over-the-counter (OTC) medication, dietary supplements (vitamins included except vitamin D supplements provided during the study and prescreening) within 2 weeks prior to dosing. In any such case, subject selection will be at the discretion of the Principal Investigator.
12.Consumption of grapefruit or grapefruit products within 72 hours prior to dosing.
13.Donation of blood (1 unit or 350 mL) or receipt of an investigational drug or product or participation in a drug research study within 6 months prior to receiving the dose of the study medicine.
14.A history of difficulty with donating blood.
15.Significant illness within two (2) weeks prior to dosing.
16.Recent (within the last three [3] years) and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc).
17.Recent (within the last three [3] years) and/or recurrent history of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated).
18.History of any food allergies.
19.Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study.
Study & Design
- Study Type
- BA/BE
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To compare the pharmacokinetic parameters of Intas Denosumab <br/ ><br>against Xgeva (US) and Xgeva (EU)Timepoint: Pre-dose, 4.000, 12.000, 24.000, 48.000, 72.000, 96.000, 120.000, 168.000, 216.000, 264.000, 312.000, 360.000, 408.000, 504.000, 672.000, 1008.000, 1344.000, 1680.000, 2016.000, 2352.000, 2688.000, 3024.000, 3360.000, 3696.000, 4032.000, 4704.000, 5376.000 and 6048.000 hours post-dose
- Secondary Outcome Measures
Name Time Method To compare the pharmacodynamic parameters of Intas <br/ ><br>Denosumab against Xgeva (US) and Xgeva (EU) <br/ ><br>To compare the immunogenicity of Intas Denosumab against <br/ ><br>Xgeva (US) and Xgeva (EU) <br/ ><br>To compare the safety of Intas Denosumab against Xgeva (US) <br/ ><br>and Xgeva (EU) <br/ ><br>To compare the pharmacokinetic and pharmacodynamic <br/ ><br>parameters of Xgeva (US) and Xgeva (EU)Timepoint: PK: Pre-dose, 4, 12, 24, 48, 72, 96, 120, 168, 216, 264, 312, 360, 408, 504, 672, 1008, 1344, 1680, 2016, 2352, 2688, 3024, 3360, 3696, 4032, 4704, 5376 and 6048 hrs post-dose <br/ ><br>PD: Pre-dose, 24, 72, 120, 168, 216, 264, 312, 360, 408, 504, 672, 1008, 1344, 2016, 2688, 3360 and 4032 and 6048 hrs post-dose. <br/ ><br>Immunogenicity: Pre-dose, Day 14, Weeks 4, 8, 12, 24, 36