| CTRI Number |
CTRI/2014/01/004325 [Registered on: 17/01/2014] Trial Registered Prospectively |
| Last Modified On: |
18/09/2015 |
| Post Graduate Thesis |
No |
| Type of Trial |
BA/BE |
|
Type of Study
|
|
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
A clinical study to measure the bioequivalence between three formulations of Leuprolide Acetate 11.25 mg (two test formulations of Daewoong and reference formulation of Takeda Pharma) in prostate carcinoma subjects. |
|
Scientific Title of Study
|
A Multicentric, Open-Label, Randomized, Three-Treatment, Parallel, Single-Dose Clinical Bioequivalence Study of Subcutaneous Leuprolide Acetate 11.25 mg (Luphere Depot®)-Test 1 (T1) and Leuprolide Acetate 11.25 mg (Luphere Depot®) –Test 2 (T2) of Daewoong Pharmaceuticals Co. Ltd., in comparison with Leuprolide Acetate 11.25 mg (Lucrin Depot®) – Reference (R) of Takeda Pharmaceutical Company Ltd., in Male Prostatic Carcinoma Subjects Undergoing Initial Therapy |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| CR018-13, Version 1.0 amendment 01 dated 23.09.2013 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Subhra Lahiri |
| Designation |
Associate Vice President |
| Affiliation |
AXIS Clinicals Ltd |
| Address |
1-121/1
Miyapur
Hyderabad
ANDHRA PRADESH
500049
India |
| Phone |
914040408064 |
| Fax |
914040408060 |
| Email |
Subhra.L@axisclinicals.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Subhra Lahiri |
| Designation |
Associate Vice President |
| Affiliation |
AXIS Clinicals Ltd |
| Address |
1-121/1
Miyapur
Hyderabad
ANDHRA PRADESH
500049
India |
| Phone |
914040408064 |
| Fax |
914040408060 |
| Email |
Subhra.L@axisclinicals.com |
|
Details of Contact Person
Public Query
|
| Name |
Monika Sharma |
| Designation |
Team Lead |
| Affiliation |
AXIS Clinicals Ltd |
| Address |
1-121/1
Miyapur
Hyderabad
ANDHRA PRADESH
500049
India |
| Phone |
914040408270 |
| Fax |
914040408060 |
| Email |
monika.s@axisclinicals.com |
|
|
Source of Monetary or Material Support
|
| Daewoong Pharmaceuticals Co Ltd,
501-2, Samgye-Ri, Pogok Eup,
Cheoin Gu Yongin,
Kyunggi Do- 449-814, |
|
|
Primary Sponsor
|
| Name |
Daewoong Pharmaceuticals Co Ltd |
| Address |
501-2, Samgye-Ri, Pogok Eup,
Cheoin Gu Yongin,
Kyunggi Do- 449-814,
South Korea.
|
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Daewoong Pharmaceuticals Co Ltd |
501-2, Samgye-Ri, Pogok Eup,
Cheoin Gu Yongin,
Kyunggi Do- 449-814,
South Korea.
|
|
|
Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 10 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Sankara Mahadev |
AXON Hospital |
Department of Radio-Oncology, AXON Hospital, Opposite ICICI Bank
SR Nagar
Ameerpet Main Road
Hyderabad
ANDHRA PRADESH |
914044505555
drdoddala@gmail.com |
| Dr Shailesh Shah |
Body Line Hospitals Pvt Ltd |
Opp Annapurna Hall Beside Dev Status New Vikas Gruh Road Paldi Ahmedabad 380007
Ahmadabad
GUJARAT |
919824035673
07926641658
shaileshshahuro@yahoo.com |
| Dr Kim Mammen |
Christian Medical College |
Department of Urology
Ludhiana
Ludhiana
PUNJAB |
911612600685
kjmammen@gmail.com |
| Dr Kapil P Thakkar |
Excel hospital |
Deapartment of Urology, 8-15, 3rd Floor,
Sheetal stopping Swuare (Old LB Cinema),
ghod-dod Bhattar road junction
Surat
GUJARAT |
912612236036
kapilthakkar@gmail.com |
| Dr Murali Subramanian |
Gurushree Hi-Tech Multi Speciality Hospital |
No 1558 Opp Chandra Layout Bus Stand
Chandra Layout Vijaynagar
Bangalore 560 040
Bangalore
KARNATAKA |
919945813327
918023394781
muralis_14@yahoo.com |
| DrRavi Agarwal |
Manu Hospital and Research Centre |
A 1 Shyam Nagar Sodala Jaipur 302019
Jaipur
RAJASTHAN |
919829064940
01412293800
dr_raviagrawal@rediffmail.com |
| Dr Yathish Kumar |
NRR Hospital |
Department of Oncology, NRR Hospital, Near Janapriya apartment
chikkasandra(Near Chikkabanavara Railway Station)
Hesargatta main road
Bangalore
KARNATAKA |
918028374115
dryathish@hotmail.com |
| Dr Sudhir Rawal |
Rajiv Gandhi Cancer Institute and Research Centre |
Consulting room no 2058
B Block
Old Building
Sector 5 Rohini
West
DELHI |
911147022027
dr_rawal@hotmail.com |
| Dr Anil Mandhani |
Sanjay Gandhi Post Graduate Institute of Medical Sciences |
Department of Urology and renal transplantation,
Sanjay Gandhi Post Graduate Institute of Medical Sciences Raebareli Road, Luknow-226014
Uttarpradesh, India
Lucknow
UTTAR PRADESH |
915222494137
anilpall@yahoo.com |
| DrKCLakshmaiah |
Srinivasam Cancer Care Hospital |
No- 236/1 , Vijayashree Layout , Arekere, Bannerghatta Main Road, Bangalore -560072
Bangalore
KARNATAKA |
919448055949
08042099074
kcluck@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 9 |
| Name of Committee |
Approval Status |
| AXON Institutional Ethics Committee |
Approved |
| Bodyline Hospitals Institutional Ethics Committee |
Approved |
| Divyam ethics Committee |
Approved |
| Institutional Ethics committe, NRR Hospital, Banglore |
Approved |
| Institutional Ethics Committee |
Approved |
| Institutional Ethics Committee |
Approved |
| InstitutionalEthicsCommittee |
Approved |
| Rajiv Gandhi Cancer Institute And Research Centre |
Approved |
| SCCH Institutional Ethics Committee |
Approved |
|
Regulatory Clearance Status from DCGI
Modification(s)
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Prostate carcinoma , |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Lucrin Depot(Leuprolide 11.25 mg) |
Subcutaneous 3 month depot |
| Intervention |
Luphere Depot (Leuprolide 11.25 mg injection)-Batch 2 |
Subcutaneous 3 month depot |
| Intervention |
Luphere Depot(Leuprolide 11.25 mg injection)-Batch 1 |
Subcutaneous 3 month depot |
|
|
Inclusion Criteria
|
| Age From |
45.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Male |
| Details |
1. Male subjects with body mass index (BMI) between 18 and 30kg/m2 (inclusive) and aged between 45 and 75 years (both inclusive) with histologically confirmed carcinoma of prostate undergoing initial therapy with Leuprolide acetate 11.25mg 3 months depot preparation.
2. Testosterone levels ≥1.5ng/mL at screening.
3. WHO ECOG performance status between 0 and 2 (inclusive) and an expected survival of ≥ 12months .
4. Subjects having adequate hematologic reserve at screening as per principal investigator/sub investigator assessment.
5. Subjects having adequate and stable hepatic function and renal function at screening as per principal investigator/sub investigator assessment.
6. Subjects having normal ECG, chest X-ray (PA view) and spinal X-ray (Lateral view).
7. No intake of any medicinal preparations, rendering expressed influence on hemodynamic, liver functions etc (e.g., barbiturate, omeprazole, cimetidine etc.) Less than for 30 days prior to the study check-in.
8. No history of dehydration from diarrhea, vomiting or any other reason within a period of 24 hours prior to study check-in.
9. Negative results for drugs of abuse in urine during the day of study check-in.
10. Negative alcohol breath analysis during the study check-in.
11. Subject should have given written informed consent to participate in the study.
12. Subjects having ability to comprehend the full nature and purpose of the study, including possible risks and adverse events; ability to co-operate with the Investigator and to comply with the requirements of the entire study.
|
|
| ExclusionCriteria |
| Details |
1. Evidence of severe urinary tract obstruction with anticipated urinary retention, in the opinion of the Investigator, taking into account medical history, clinical observations and symptoms.
2. History of chronic fatigue or worsening general health.
3. History of osteoporosis or bone pains.
4. History of tobacco ( 9 cigarettes/beedies per day) or alcohol abuse within past 3 months of screening.
5. History of intake of anticonvulsants and corticosteroids or any other drug known to decrease bone density.
6. History or evidence of thrombophlebitis, thromboembolic disorders, cerebral apoplexy.
7. Excruciating, severe bone pain which is due to from extensive metastatic osseous deposits (in the opinion of the Investigator), taking into account medical history, clinical observations and symptoms.
8. Evidence of brain metastases, taking into account medical history, clinical observations and symptoms (as decided by the investigator).
9. History of systemic therapy for cancer such as chemotherapy, radiotherapy or immunotherapy (e.g., antibody therapies, tumor-vaccines), biological response modifiers (e.g., cytokines) within 3 months of screening or previous local therapy to the primary tumor (external beam radiotherapy, brachytherapy, thermotherapy, cryotherapy).
10. History of prostatic surgery (e.g., radical prostatectomy, transurethral resection of the prostate [TUR-P]) or orchiectomy, adrenalectomy or hypophysectomy.
11. Intake of any investigational drugs within 5 half-lives of its physiological action or 3 months (whichever is longer) before screening.
12. Previous treatment with AR-receptor blockers, such as Casodex®, Fugerel®, Megace®, Androcur® (no wash-out allowed) or 5-α-reductase inhibitors (Proscar®, Avodart®, Propecia®) or Over-the-counter (OTC) or alternative medical therapies which have an estrogenic or anti-androgenic effect (i.e., PC-SPES, saw palmetto, Glycyrrhiza®, Urinozinc®, DHEA) within the 3 months before screening .
13. Administration of hormonal therapy, including GnRH analogs (except Leuprolide acetate 11.25 mg 3 months depot preparation) (less than or equal to 6 month depot administration), estrogen, megace and phytotherapy, within 32 weeks prior to the screening visit and during the study.
14. History of uncontrolled diabetes mellitus.
15. History of blood donations/losses within 3 months of screening.
16. Subjects with known hypersensitivity to GnRH, GnRH agonist, including any LHRH analogues, or any excipients of the study formulation.
17. History of any coagulation or bleeding abnormality
18. History of venous thrombosis within 6 months prior to baseline.
19. Significant Pre-existing co-morbidities
a. Cardiovascular
• Myocardial infarction within the last 6 months
• Congestive heart failure
• Unstable angina
• Active cardiomyopathy
• Cardiac arrhythmia
• Uncontrolled hypertension
• History of familial long QT syndrome or sudden cardiac death
b. Pulmonary
• Pulmonary disease requiring oxygen
c. Neurologic and psychiatric
• History of significant neurologic or psychiatric disorder that would preclude study compliance or ability to give informed consent.
d. Gastrointestinal (GI)
• GI conditions that would preclude compliance with oral medication
e. Other cancer(s)
• Other malignancy than carcinoma of prostate within the past 5 years.
20. Subjects positive for HIV 1 & 2/HBsAg/HCV at screening.
21. Any deviation from a normal diet e.g. religious fasting.
22. Consumption of grape fruit juice within the 48 hours prior to study check-in.
23. High caffeine (more than 5 cups of coffee or tea/day).
24. History of any disorder that interferes with the blood sampling during the study.
|
|
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Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
• Cmax
• AUC 0- 42 Day |
• Day1,3,7,14,21,28,35 and Day 42 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
• Tmax: Time of the maximum measured serum concentration.
• Safety and tolerability
|
Timepoint: Day1,3,7,14,21,28,35 and Day 42 |
|
|
Target Sample Size
|
Total Sample Size="42"
Sample Size from India="42"
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
20/01/2014 |
| 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="1"
Months="6"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
|
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
This study is Multicentric, Open-Label, Randomized, Three-Treatment, Parallel, Single-Dose Clinical Bioequivalence Study of Subcutaneous Leuprolide Acetate 11.25 mg (Luphere Depot®)-Test 1 (T1) and Leuprolide Acetate 11.25 mg (Luphere Depot®) –Test 2 (T2) of Daewoong pharmaceuticals Co. Ltd., in comparison with Leuprolide Acetate 11.25 mg (Lucrin Depot®) – Reference (R) of Takeda Pharmaceutical Company Ltd., in Male Prostatic Carcinoma Subjects Undergoing Initial Therapy.
The Primary objective will be to determine clinical bioequivalence of test drug (T1 & T2) with the active comparator (reference drug). The secondary objective of the study is to monitor the adverse events, to ensure safety and tolerability as assessed by reported adverse events, laboratory, clinical investigations and vital signs in the prostate carcinoma patients. |