| CTRI Number |
CTRI/2022/03/041280 [Registered on: 22/03/2022] Trial Registered Prospectively |
| Last Modified On: |
08/09/2022 |
| Post Graduate Thesis |
No |
| Type of Trial |
BA/BE |
|
Type of Study
|
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| Study Design |
Randomized, Crossover Trial |
|
Public Title of Study
|
A multicenter, open label study of hydroxyurea capsules in sickle cell anemia patients already on stable regimens of hydroxyurea, |
|
Scientific Title of Study
|
A multicenter, open label, balanced, randomized, single-dose, two-treatment, two period, crossover, bioequivalence study of hydroxyurea capsules 500 mg of Qilu Pharmaceutical Co., Ltd., China with that of HYDREA (hydroxyurea) capsules 500 mg of Bristol-Myers Squibb Company, Princeton, New Jersey 08543 USA in sickle cell anemia patients already on stable regimens of hydroxyurea, under fasting conditions. |
| Trial Acronym |
|
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Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 21-VIN-0405 Version 02 dated 29 Nov 2021 |
Protocol Number |
|
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
DrSumit Arora |
| Designation |
Vice President Clinical Operations |
| Affiliation |
Veeda Clinical Research Ltd |
| Address |
Veeda Clinical Research Ltd.,
Shivalik Plaza, Near I.I.M.,
Ambawadi, Ahmedabad 380 015, Gujarat, India
Ahmadabad
GUJARAT
380015
India |
| Phone |
07930013000 |
| Fax |
|
| Email |
Sumit.arora@veedacr.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Ravi Alamchandani |
| Designation |
General Manager |
| Affiliation |
Veeda Clinical Research Ltd |
| Address |
Veeda Clinical Research Ltd.,
Shivalik Plaza, Near I.I.M.,
Ambawadi, Ahmedabad 380 015, Gujarat, India
Ahmadabad
GUJARAT
380015
India |
| Phone |
07930013000 |
| Fax |
|
| Email |
Ravi.A1950@veedacr.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Ravi Alamchandani |
| Designation |
General Manager |
| Affiliation |
Veeda Clinical Research Ltd |
| Address |
Veeda Clinical Research Ltd.,
Shivalik Plaza, Near I.I.M.,
Ambawadi, Ahmedabad 380 015, Gujarat, India
GUJARAT
380015
India |
| Phone |
07930013000 |
| Fax |
|
| Email |
Ravi.A1950@veedacr.com |
|
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Source of Monetary or Material Support
|
| Qilu Pharmaceutical Co., Ltd |
|
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Primary Sponsor
|
| Name |
Qilu Pharmaceutical Co Ltd |
| Address |
No. 23999 Gong Ye Bei Road,
Jinan, 250100, China (CHN)
|
| Type of Sponsor |
Pharmaceutical industry-Global |
|
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Details of Secondary Sponsor
|
| Name |
Address |
| Veeda Clinical Research Ltd |
Shivalik Plaza, Near I.I.M.,
Ambawadi, Ahmedabad 380 015, Gujarat, India
Phone: 91 079 3001 3000
|
|
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Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 4 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Gaurish Gadbail |
Nirmal Hospital Pvt. Ltd. |
Nirmal Hospital Pvt Ltd, Ring Road, Surat- 395002, Gujarat, India
Surat
GUJARAT |
9377113143
dr.gaurishgadbail@gmail.com |
| Dr Manish Hathila |
Shakti Research Centre |
Shakti Research Centre, A-108, 1st floor, Krishna Complex, B/H Shahwadi Bus stop,NH-8,Narol, Ahmedabad-382405, Gujarat, India.
Ahmadabad
GUJARAT |
9428415979
manishathila@gmail.com |
| Dr Prakash Kurmi |
Shivam Hospital |
C-4, Satyanarayan Society, Gor’s Kuvo, Jashodanagar Char Rasta, Maninagar, Ahmedabad-380008
Ahmadabad
GUJARAT |
9825047692
dr.prakashkurmi@yahoo.com |
| DrKeyur Brahme |
SSG Hospital and Medical College |
Department of Medicine, Sir Sayajirao General Hospital and Medical College-Baroda, Jail Road, Indian Avenue, Vadodara, Gujarat, 390001
Vadodara
GUJARAT |
9727729105
keyurbrahme@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 4 |
| Name of Committee |
Approval Status |
| Institutional ethics committee for Human Research |
Approved |
| Nirmal Hospital Pvt. Ltd. Ethics Committee |
Approved |
| Shivam Ethics committee |
Approved |
| Vrajesh Hospital Institutional Review Board |
Approved |
|
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Regulatory Clearance Status from DCGI
|
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: D571||Sickle-cell disease without crisis, |
|
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Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
HYDREA (hydroxyurea) capsules 500
mg of Bristol-Myers Squibb Company, Princeton, New Jersey 08543 USA |
The patient will receive single dose of Reference in each period [day 1 (period I) and day 8 (period II)The patient will receive total 2 doses- one on day 1 & second on day 8.The duration will be 8 days. |
| Intervention |
Hydroxyurea capsules 500 mg of Qilu Pharmaceutical Co., Ltd., China |
The patient will receive single dose of test
in each period [day 1 (period I) and day 8 (period II)]. The patient will receive total 2 doses- one on day 1 & second on day 8. The duration will be 8 days. |
|
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Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
1. Patients of either gender (Male or Female) ≥18 years of age with confirmed diagnosis of sickle cell anemia.
2. Patients that are already on a stable dosing regimen of hydroxyurea (500 mg taken once daily) for at least 24 weeks prior to screening in the study.
3. Willing to give written informed consent for participation in the trial as well as willing and able to comply with study visit schedule and other protocol requirements.
4. Adequate Hematopoietic, Renal and Hepatic function defined as the following:
Body system Parameters
Bone marrow function ANC  1500/mm3
Platelet count  100,000/mm3
Haemoglobin > 9.0 g/dl
Hepatic function ALT/AST ≤ 2.5 × ULN
Total Bilirubin ≤ 1.5 ×ULN
Renal function Creatinine clearance ≥ 60 ml/min (calculated based on Cockcroft-Gault formula)
5. Able to comply with study requirement in opinion of Principal Investigator.
6. Females of childbearing potential must have a negative beta-HCG pregnancy test at screening and negative urine pregnancy test at the time of check-in.
7. Sexually active women, unless surgically sterile (at least 6 months prior to study drug administration) or postmenopausal for at least 12 consecutive months, must use an effective method of avoiding pregnancy [including oral, transdermal, or implanted contraceptives (any hormonal method in conjunction with a secondary method), intrauterine device, female condom with spermicide, diaphragm with spermicide, absolute sexual abstinence, use of condom with spermicide by sexual partner or sterile (at least 6 months prior to study drug administration) sexual partner] during study and for atleast 6 months after the last dose of study drug.
Cessation of birth control after this point should be discussed with a responsible physician.
8. Males of reproductive potential must agree to use effective contraception [including use of barrier methods (male condom, spermicide), behavioral methods (abstinence) or vasectomy] or the female partners of these patients must agree to use an effective method of avoiding pregnancy as defined in the inclusion criteria no. 7, during the study and for atleast 1 year after the last dose of study drug.
Cessation of birth control after this point should be discussed with a responsible physician It is investigator responsibility to ensure that above points regarding an effective method of avoiding pregnancy are discussed with patient or legally acceptable representative LAR in detail and patient agreed for this and it is documented in source document. The investigator should ensure that the patient is using an effective method of avoiding pregnancy as per protocol LAR is an individual or juridical or other body authorised under applicable law to represent the interests of an individual including providing consent on behalf of a prospective subject to the subject participation in the clinical trial. |
|
| ExclusionCriteria |
| Details |
1. History of hypersensitivity to hydroxyurea or any other component of its formulation as judged by the investigator.
2. History of a myeloproliferative disease, diffuse pulmonary infiltrates or pulmonary fibrosis.
3. History of therapy with central nervous system inhibitor or antitumor agents (e.g. 5-fluorouracil) within 28 days before the first administration of investigational product.
4. History of therapy with interferon or antiretroviral agents (e.g. didanosine, stavudine and indinavir) within 28 days before the first administration of investigational product.
5. Patients with leukemia of any type.
6. Uncontrolled systemic infection.
7. Cardiac diseases including congestive heart failure, atrial or ventricular arrhythmia.
8. History of drug/alcohol addiction.
9. Pregnant or lactating females.
10. Patients found to be positive for HIV, Hepatitis B or C, VDRL at screening.
11. Patients requiring dosing with any of the live vaccines.
12. Patients suffering from gout.
13. Patients with skin cancer or other secondary malignancies.
14. Patients with cutaneous vasculitic toxicities, including vasculitic ulcerations, gangrene, etc.
15. Patients with history of diagnosis of macrocytosis or pernicious anemia.
16. Patients with a history of tumor lysis syndrome, disorientation, hallucinations, convulsions etc. following treatment with hydroxyurea.
17. Patients who have received radiation therapy in the past for any reason.
18. Donation of blood (1 unit or 350 mL) within 90 days prior to receiving the first dose of IMP.
19. Inadequate venous access for PK sampling as judged by investigator.
20. Requirement of any planned procedure or hospitalization for pre-existing conditions during the study period.
21. Patients found positive on urine scan for drugs of abuse and/or breath / other relevant test for alcohol consumption at screening and baseline.
22. The receipt of an investigational medicinal product or participation in other drug research study within a period of 30 days (or 5 half-lives, whichever is longer) prior to the first dose of investigational medicinal product for the current study.
Note: Elimination half-life of the study drug should be taken in to consideration for inclusion of the patient in the study.
23. Patients with any significant history of non-compliance or inability to reliably grant informed consent.
24. Significant blood loss/hemorrhage leading to hemodynamic instability as judged by Investigator.
25. Patients in whom oral administration of IMP is not possible
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Method of Generating Random Sequence
|
Computer generated randomization |
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Method of Concealment
|
An Open list of random numbers |
|
Blinding/Masking
|
Open Label |
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Primary Outcome
|
| Outcome |
TimePoints |
To assess the bioequivalence of test product (hydroxyurea capsules 500 mg) of
Qilu Pharmaceutical Co., Ltd., China with that of reference product HYDREA
(hydroxyurea) capsules 500 mg of Bristol-Myers Squibb Company, Princeton,
New Jersey 08543 USA in sickle cell anemia patients already receiving a stable
dosing regimen of hydroxyurea under fasting conditions. |
A total of 24 blood samples for PK assessment in period I(visit 2) & period II (visit 3),The pre-dose blood sample of 4 mL will be collected within one hour prior to the dosing. |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
To monitor the safety and tolerability profile of the study formulations in sickle
cell anemia patients. |
At (Screening)visit 1,visit 2(day 1),visit 3(day 8), and EOS
visit, there will be physical examination, vitals
signs will be performed by investigator. |
|
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Target Sample Size
|
Total Sample Size="36"
Sample Size from India="36"
Final Enrollment numbers achieved (Total)= "32"
Final Enrollment numbers achieved (India)="32" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
05/04/2022 |
| Date of Study Completion (India) |
28/06/2022 |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="0"
Months="4"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
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Publication Details
|
NIL |
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
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Brief Summary
|
Post randomization patients will receive single dose of either test or reference product
in each period [day 1 (period I) and day 8 (period II)]. There will be washout of 7
days between each period.
During the wash out period, patients will continue to receive locally marketed
hydroxyurea.
Note:
ï‚· For period II, a window period of +7 days may be allowed for any social reason
or any other unavoidable circumstances etc. and +14 days may be allowed for AE
management.
ï‚· Dosing activity will be done under sodium vapor lamp in both periods.
Patients will be administered drug in sitting position posture. Patients will be advised
to remain in sitting or ambulatory position for the first 04 hours after IMP
administration. Patients will be advised to avoid any strenuous activity throughout
study period. Thereafter, the patients will be allowed to engage only in normal
activities while avoiding severe physical exertion.
Patients will be housed in clinical facility at least 12 hrs prior to scheduled dosing in
each period. Patients will continue to remain in the facility for at least 24 hours after
dosing in each period.
The patients will have to stay at least 2 consecutive nights in clinical facility in each
period.
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