A multicenter, open label study of hydroxyurea capsules in sickle cell anemia patients already on stable regimens of hydroxyurea,

Not Applicable

Completed

• Conditions: Health Condition 1: D571- Sickle-cell disease without crisis

• Registration Number: CTRI/2022/03/041280
• Lead Sponsor: Qilu Pharmaceutical Co Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Completion: 2022-06-28
• Last Update Posted: 17 October 2022

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 32

Inclusion Criteria

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 systemParameters

Bone marrow functionANC ïâ??³ 1500/mm3

Platelet count ïâ??³ 100,000/mm3

Haemoglobin > 9.0 g/dl

Hepatic functionALT/AST ââ?°Â¤ 2.5 Ã?â?? ULN

Total Bilirubin ââ?°Â¤ 1.5 Ã?â??ULN

Renal functionCreatinine 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.

Exclusion Criteria

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

Study & Design

• Study Type: BA/BE
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To assess the bioequivalence of test product (hydroxyurea capsules 500 mg) of <br/ ><br>Qilu Pharmaceutical Co., Ltd., China with that of reference product HYDREA <br/ ><br>(hydroxyurea) capsules 500 mg of Bristol-Myers Squibb Company, Princeton, <br/ ><br>New Jersey 08543 USA in sickle cell anemia patients already receiving a stable <br/ ><br>dosing regimen of hydroxyurea under fasting conditions.Timepoint: 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 Measures

Name	Time	Method
To monitor the safety and tolerability profile of the study formulations in sickle <br/ ><br>cell anemia patients.Timepoint: At (Screening)visit 1,visit 2(day 1),visit 3(day 8), and EOS <br/ ><br>visit, there will be physical examination, vitals <br/ ><br>signs will be performed by investigator.