| CTRI Number |
CTRI/2011/12/002257 [Registered on: 19/12/2011] Trial Registered Prospectively |
| Last Modified On: |
16/07/2013 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Biological |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
A six month randomized, double-blind, placebo controlled study across centres in India to study the safety and efficacy of Denosumab in post menopausal women with osteoporosis |
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Scientific Title of Study
|
A Six-Month, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy and Safety of Denosumab in Indian Postmenopausal Women with Osteoporosis.
.
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| Trial Acronym |
|
Secondary IDs if Any
Modification(s)
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| Secondary ID |
Identifier |
| DPH114161-Denosumab |
Other |
|
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
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| Name |
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| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
|
| Name |
Dr Jeroze Dalal |
| Designation |
General Manager |
| Affiliation |
GlaxoSmithKline |
| Address |
252, Dr. A.B. Road,
Worli
Mumbai
MAHARASHTRA
400030
India |
| Phone |
0222495395 |
| Fax |
02224947415 |
| Email |
jeroze.j.dalal@gsk.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Vipul Halbe |
| Designation |
Clinical Trial Leader |
| Affiliation |
GlaxoSmithKline |
| Address |
252, Dr. A.B. Road,
Worli
Mumbai
MAHARASHTRA
400030
India |
| Phone |
0222495584 |
| Fax |
02224947415 |
| Email |
vipul.s.halbe@gsk.com |
|
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Source of Monetary or Material Support
|
| GlaxoSmithKline Pharmaceuticals Ltd. |
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Primary Sponsor
|
| Name |
GlaxoSmithKline Pharmaceuticals Ltd |
| Address |
GlaxoSmithKline Pharmaceuticals Ltd.
252, Dr. A.B. Road,
Mumbai 400030.
India. |
| Type of Sponsor |
Pharmaceutical industry-Global |
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Details of Secondary Sponsor
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Countries of Recruitment
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India |
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Sites of Study
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| No of Sites = 12 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Prasanna Kumar |
Bangalore Diabetes Hospital |
Ground Floor, Shriman Complex,
16/M
Thimmiah Road, Millers Tank Bed Area
Vasanth Nagar Post,
Bangalore – 560052, India
Bangalore
KARNATAKA |
080-22372980
08022372981
dr.knpk@gmail.com |
| Dr Bharat Mody |
Centre for Knee and Hip Surgery |
101/103 Akashganga Complex,
Near Vunijya Bhavan,
Race Course Circle,
Vadodra – 390007, India
Vadodara
GUJARAT |
919824036065
0265-2338030
joints.mody@gmail.com |
| Dr Vaishali Deshmukh |
Deshmukh Clinic & Research Centre |
4th Floor, Mulay Arcade,
Next to Maharashtra Mandal School, Tilak Road,
Pune – 411030, India
Pune
MAHARASHTRA |
919850811450
020-24436938
docvaishali@yahoo.co.in |
| Dr Jacob Chacko |
Father Muller Medical College |
Department of Orthopedics.
Kankanady,
Mangalore. Karnataka 575002.
India.
Bangalore
KARNATAKA |
08242238000
08242437402
chackojakes@yahoo.co.in |
| Dr Mathew Thomas |
Health and Research Centre |
1st floor Devi Scans Building. Kumarapuram, Medical College, Trivandrum 695011, Kerela. India.
Thiruvananthapuram
KERALA |
04712554911
04712554913
amnavita@gmail.com |
| Dr Sanjay Reddy |
Medisys Clinisearsh India Private Ltd.Bangalore Diabetes Centre |
No. 4C-426, 4th Cross,
2nd Block, Kalyan Nagar,
Bangalore – 560043, India
Bangalore
KARNATAKA |
08025421333
08025425496
drsanjayreddy@yahoo.com |
| Dr Naresh Shetty |
MS Ramaiah College and Hospital |
Dept. of Orthopedics and Clinical Research. New Bel Road,
MSRIT post, Bangalore – 560054, India
Bangalore
KARNATAKA |
080-40503274
080-40528402
nareshs8@hotmail.com |
| Dr Shailesh Pitale |
Pitale Diabetes & Hormone Centre |
Ground Floor, Shriman Complex,
Near Lokmat Square,
Dhantoli,
Nagpur – 440012, India
Nagpur
MAHARASHTRA |
0712-2457176
0712-2420465
drpitale@yahoo.co.in |
| Dr Gaurav Rathi |
Sanjivani Super Specilaity |
1, New Uday Park Society,
Near Sunrise Park,
Vastrapur,
Ahmedabad – 380015, India
Ahmadabad
GUJARAT |
079-2635610
079-26307165
drgjrathi@yahoo.co.in |
| Dr Atul Kakar |
Sir Ganga Ram Hospital |
Dept. of Medicine.
Sir Ganga Ram Hospital.
New Delhi
DELHI |
01143594466
01125861002
atulkakar@hotmail.com |
| Dr AVG Reddy |
Sunshine Hospital |
Dept. of Orthopedics. P G Road, Opp. Parsi Dharamsala, Besides Paradise Hotel, Secunderabad 500003.
Hyderabad
ANDHRA PRADESH |
04064636363
04027890091
guravareddy@gmail.com |
| Dr Sushrut Babhulkar |
Sushrut Hospital & Research Centre |
30-B, Central Bazaar Road,
Ramdaspeth,
Nagpur-440010. India.
Nagpur
MAHARASHTRA |
0712-2424062
0712-2430065
sushrutdsurgeon@gmail.com |
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Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 12 |
| Name of Committee |
Approval Status |
| Bangalore Diabetes Hospital Ethics Committee |
Approved |
| Clinicom -Committee for Evaluation of Protocols for Clinical Research |
Approved |
| Ethics Committee of Centre for Knee Surgery |
Approved |
| Father Muller Institutional Ethics Committee |
Approved |
| Independent Ethics Committee, Nagpur |
Approved |
| Independent Human Ethics Committee, Health and Research Centre |
Approved |
| Institutional Ethics Committee Sunshine Hospitals |
Approved |
| M.S.Ramaiah Hospital Ethical Review Board |
Approved |
| Medisys Clinisearch Ethical Review Board |
Approved |
| Rathi Ethics Committee |
Approved |
| Sir Ganga Ram Hospital Ethics Committee |
Approved |
| Sushrut Hospital Ethics Committee |
Approved |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
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| Health Type |
Condition |
| Patients |
Post-Menopausal Osteoporosis , |
|
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Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Denosumab |
Denosumab 60 mg will be administered as a single subcutaneous (SC) injection during the Double-Blind phase. |
| Comparator Agent |
Placebo |
Placebo will be administered as a single subcutaneous (SC) injection during the Double-Blind phase. |
|
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Inclusion Criteria
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| Age From |
55.00 Year(s) |
| Age To |
75.00 Year(s) |
| Gender |
Female |
| Details |
1. Subject is willing and able to provide written informed consent.
2. Of Indian origin – defined as a person having origins from the Indian subcontinent
(India, Pakistan, Bangladesh and Sri Lanka).
3. Ambulatory woman between the age of 55and 75 years, inclusive.
4. The subject has a BMD absolute value consistent with a T-score < -2.5 and > -4.0 at
either the lumbar spine or total hip. [Table 2 provides BMD equivalents by T-score
thresholds for each DXA scanner manufacturer. The BMD equivalent for
corresponding T-score must be < -2.5 and > -4.0 for a subject to be eligible].
5. Postmenopausal defined as >5-years postmenopausal, which can be >5-years of
spontaneous amenorrhea or >5-years post surgical bilateral oophorectomy. Use
follicle stimulating hormone (FSH) levels > 40 mIU/mL to confirm surgical
postmenopausal status, where bilateral oophorectomy status is uncertain. |
|
| ExclusionCriteria |
| Details |
Previous or Current Medical Conditions:
1. Bone/metabolic disease:
a. Any metabolic bone disease, e.g., osteomalacia or osteogenesis imperfecta,
which may interfere with the interpretation of the findings.
b. Paget’s disease
c. Cushing’s disease
d. Hyperprolactinemia
2. Current hyperparathyroidism or hypoparathyroidism
3. Thyroid condition: Hyper- or hypothyroidism; however, subjects on stable thyroid
hormone replacement therapy may be allowed per the following criteria:
a. If TSH level is below normal range, subject is not eligible for the study.
b. If TSH level is elevated ( 5.5 μIU/mL to 10.0 μIU/mL), serum T4 should be
measured.
• If serum T4 is within normal range, subject is eligible.
• If serum T4 is outside of normal range, subject is not eligible for the study.
c. If TSH level is above 10.0 μIU/mL, subject is not eligible.
4. Rheumatoid arthritis
5. Malignancy:
a. Malignancy (except fully resected cutaneous basal cell or squamous cell
carcinoma, cervical or breast ductal carcinoma in situ) within the last 5-years.
6. Malabsorption syndrome: malabsorption syndrome or any gastrointestinal
disorders associated with malabsorption.
7. Liver disease:
a. Cirrhosis of the liver
b. Unstable liver disease (as defined by the presence of ascites, encephalopathy,
coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent
jaundice), known biliary abnormalities (with the exception of Gilbert’s
syndrome or asymptomatic gallstones). Chronic stable hepatitis B and C are
acceptable, if subject otherwise meet study entry criteria (e.g., presence of
hepatitis B surface antigen or positive Hepatitis C test result within 3-months of
Screening).
8. Drug or alcohol abuse: Evidence of alcohol or substance-abuse within the last
12-months which the Investigator believes would interfere with understanding or
completing the study.
9. Biological abnormalities:
a. Any disorder that compromises the ability of the subject to give written
informed consent or to comply with study procedures.
b. Any physical or psychiatric disorder which, in the opinion of the Investigator,
will prevent the subject from completing the study or interfere with the
interpretation of the study results.
c. Known to have tested positive for human immunodeficiency virus (HIV).
10. Vitamin D deficiency: Vitamin D deficiency (25-(OH) vitamin D level
20 ng/mL). Vitamin D repletion will be permitted and subjects may be re-tested
with 25-(OH) vitamin D.
11. 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.
d. Non-healed dental or oral surgery.
Concomitant Medications:
12. Previous strontium or IV bisphosphonate: Administration of intravenous (IV)
bisphosphonate, fluoride, or strontium for osteoporosis within the last 5-years.
13. Oral bisphosphonate: Oral bisphosphonate treatment for osteoporosis:
a. If used for ≥3-years cumulatively, subject is ineligible.
b. If used for 3-months but 3-years cumulatively:
• If the last dose was 1-year before enrolment, subject is ineligible.
• If the last dose was ≥1-year before enrolment, subject is eligible.
c. If used ≤3-months, cumulatively, subject is eligible.
14. Bone metabolism drugs: Administration of any of the following treatments within
the last 6-weeks:
a. Parathyroid hormone (PTH) or PTH derivatives, e.g., teriparatide.
b. Anabolic steroids or testosterone.
c. Glucocorticosteroids (5 mg prednisone equivalent per day for more than
10-days).
d. Systemic hormone replacement therapy.
e. Selective estrogen receptor modulators (SERMs), e.g., raloxifene
f. Tibolone
g. Calcitonin
h. Calcitriol or vitamin D derivatives
i. Other bone active drugs including anti-convulsives (except benzodiazepines)
and heparin.
j. Chronic systemic ketoconazole, androgens, ACTH, cinacalcet, aluminum,
lithium, protease inhibitors, methotrexate, gonadotropin-releasing hormone
agonists.
15. Investigational drug exposure: Currently enrolled in or has not yet completed at
least 30-days since ending other investigational device or drug trial(s), or subject is
receiving other investigational agent(s).
16. Sensitivity: Known sensitivity to mammalian cell derived drug products.
Abnormal laboratory values
17. General: Any laboratory abnormality which, in the opinion of the Investigator, will
prevent the subject from completing the study or interfere with the interpretation of
the study results.
18. Abnormal serum calcium: current hypocalcemia or hypercalcemia. Albuminadjusted
serum calcium levels must be within normal limits of the central laboratory.
19. Liver transaminases:
a. Serum aspartate aminotransferase (AST; serum glutamate-oxaloacetic
transaminase [SGOT]) ≥2.0x upper limits of normal (ULN).
b. Serum alanine aminotransferase (ALT; serum glutamate-pyruvate transaminase
[SGPT]) ≥2.0x ULN.
c. Alkaline phosphatase and bilirubin ≥1.5xULN (isolated bilirubin ≥1.5ULN is
acceptable if bilirubin is fractionated and direct bilirubin 35%.
20. DXA measurements:
a. Less than two lumbar vertebrae evaluable for DXA measurements.
b. Height, weight, or girth which may preclude accurate DXA measurements. |
|
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Method of Generating Random Sequence
|
Computer generated randomization |
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Method of Concealment
|
Centralized |
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Blinding/Masking
|
Double Blind Double Dummy |
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Primary Outcome
|
| Outcome |
TimePoints |
| To assess between the denosumab and placebo treatment groups:Percent change in BMD at the lumbar spine from Baseline to Month 6 |
To assess between the denosumab and placebo treatment groups:Percent change in BMD at the lumbar spine from Baseline to Month 6 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| To assess between the denosumab and placebo treatment groups:Percent change in BMD at the total hip from Baseline to Month 6. |
6 month |
To assess between the denosumab and placebo treatment groups:Percent change in BMD at the femoral neck and trochanter from Baseline to Month
6. |
6 month |
| To assess between the denosumab and placebo treatment groupsPercent change in serum CTX and P1NP from Baseline to Months 1, 3 and 6. |
Month 1,3 and 6 |
|
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Target Sample Size
|
Total Sample Size="250"
Sample Size from India="250"
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" |
|
Phase of Trial
|
Phase 3 |
Date of First Enrollment (India)
Modification(s)
|
08/02/2012 |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="2"
Months="5"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
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Publication Details
|
|
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
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Brief Summary
|
The aim of this Phase III, randomized, double-blind, placebo-controlled,parallel-group, multicenter study is to evaluate the efficacy and safety of denosumab in Indian postmenopausal women with osteoporosis. The study design consists of two phases: Screening and 6-month Double-Blind treatment phase. Following theScreening phase, all eligible subjects will be randomized to receive double-blind Denosumab (60 mg) or Placebo (PBO) study medication in a 1:1 ratio. |