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Pharmacokinetics of Oral Hydroxyurea Solution (HUPK)

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ClinicalTrials.gov Identifier: NCT03763656
Recruitment Status : Completed
First Posted : December 4, 2018
Last Update Posted : February 11, 2022
Sponsor:
Information provided by (Responsible Party):
Nova Laboratories Limited

Brief Summary:
An open label, safety and pharmacokinetic study of oral hydroxyurea solution administered to children from 6 months to 17.99 years (i.e. to the day before 18th birthday), with a 12 to 15 month treatment period for each participant. The study treatment duration will be for 6 months at the maximum tolerated dose [MTD], which is usually reached by 6 months after initiation of treatment. For patients in whom time to MTD is longer than 6 months or not achieved at all, the maximum duration of study treatment will be 15 months.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Sickle-Cell; Hemoglobin Disease, Thalassemia Sickle Cell-beta-thalassemia Sickle Cell Hemoglobin C Drug: Hydroxyurea Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective Open Label, Pharmacokinetic Study of an Oral Hydroxyurea Solution in Children With Sickle Cell Anemia.
Actual Study Start Date : November 20, 2018
Actual Primary Completion Date : May 19, 2021
Actual Study Completion Date : December 29, 2021


Arm Intervention/treatment
Experimental: Open Label
Novel oral solution formulation of hydroxyurea
Drug: Hydroxyurea
Oral Hydroxyurea




Primary Outcome Measures :
  1. Clearance (CL/F) [ Time Frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose.on Day 1 and Day 2 (Week 20-36) ]
    Pharmacokinetic Parameters

  2. Volume of distribution (V/F) [ Time Frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose.on Day 1 and Day 2 (Week 20-36) ]
    Pharmacokinetic Parameters

  3. Time to maximum concentration (Tmax) [ Time Frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose.on Day 1 and Day 2 (Week 20-36) ]
    Pharmacokinetic Parameters

  4. Maximum plasma concentration (Cmax) [ Time Frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose.on Day 1 and Day 2 (Week 20-36) ]
    Pharmacokinetic Parameters

  5. Area under plasma concentration time curve (AUC) [ Time Frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose.on Day 1 and Day 2 (Week 20-36) ]
    Pharmacokinetic Parameters

  6. Half-life (t½) [ Time Frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose.on Day 1 and Day 2 (Week 20-36) ]
    Pharmacokinetic Parameters


Secondary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to Week 64 ]
    Safety

  2. Absolute neutrophil count [ Time Frame: Up to Week 60 ]
    Safety

  3. White Blood Cell Count and Differentials [ Time Frame: Up to Week 60 ]
    Safety

  4. Platelets [ Time Frame: Up to Week 60 ]
    Safety

  5. Mean Corpuscular Hemoglobin [ Time Frame: Up to Week 60 ]
    Safety

  6. Hematocrit [ Time Frame: Up to Week 60 ]
    Safety

  7. Bilirubin [ Time Frame: Up to Week 60 ]
    Safety

  8. Elevation in liver function tests (LFTs) [ Time Frame: Up to Week 60 ]
    Safety

  9. Hemoglobin/Anemia [ Time Frame: Up to Week 60 ]
    Safety

  10. Clinically significant change in hematology [ Time Frame: Up to Week 60 ]
    Safety

  11. Clinically significant change in biochemistry [ Time Frame: Up to Week 60 ]
    Safety

  12. Clinically significant change in urinalysis [ Time Frame: Up to Week 60 ]
    Safety

  13. Bacterial infections [ Time Frame: Up to Week 60 ]
    Safety

  14. Viral infections [ Time Frame: Up to Week 60 ]
    Safety

  15. Fungal infections [ Time Frame: Up to Week 60 ]
    Safety

  16. Leg ulcers [ Time Frame: Up to Week 60 ]
    Safety

  17. Fetal hemoglobin [ Time Frame: Up to Week 60 ]
    Biomarker endpoints

  18. Mean Corpuscular Volume [ Time Frame: Up to Week 60 ]
    Biomarker endpoints

  19. Cystatin C [ Time Frame: Up to Week 60 ]
    Biomarker Endpoints

  20. Incidence of acute pain crises [ Time Frame: Up to Week 60 ]
    Clinical status endpoints

  21. Number and frequency of blood transfusions [ Time Frame: Up to Week 60 ]
    Clinical status endpoints

  22. Incidence of acute chest syndrome [ Time Frame: Up to Week 60 ]
    Clinical status endpoints

  23. Hospitalizations [ Time Frame: Up to Week 60 ]
    Clinical Status endpoints

  24. Dose escalation i.e. time to maximum tolerated dose [ Time Frame: Up to Week 60 ]
    Clinical status endpoints

  25. Clinically parameters (symptoms) [ Time Frame: Up to Week 60 ]
    Clinical status endpoints

  26. Parent/caregiver palatability and acceptability: To evaluate the taste and acceptability of the new oral liquid formulation of hydroxyurea by use of a simple opinion questionnaire and visual analogue hedonic scale [ Time Frame: Up to Week 60 ]
    Clinical status endpoints


Other Outcome Measures:
  1. Transcranial Doppler velocity [ Time Frame: Up to Week 56 ]
    Exploratory

  2. Urine parameters (albumin, creatinine, for urinary ACR ratio) [ Time Frame: Up to Week 60 ]
    Exploratory



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Ages Eligible for Study:   6 Months to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female aged from 6 months to 17.99 years of age (i.e. to the day before 18th birthday).
  2. Diagnosis of sickle cell anemia (HbSS and HbSβº).
  3. Parent(s)/legal guardian able and willing to provide written informed consent for the child to take part in the study.
  4. Where applicable, the child should assent to undergo blood sampling for pharmacokinetic and biochemistry purposes and to allow physiological measurements to be made.

Exclusion Criteria:

  1. Any clinically significant medical condition or abnormality, which, in the opinion of the investigator, might compromise the safety of the patient or which might interfere with the study.
  2. Hydroxyurea use within 6 months before enrolment.
  3. Renal insufficiency (known creatinine more than twice the upper limit of normal (ULN) for age and > 1.0 mg/dL [88.4 micromol/L])
  4. Clinical evidence of hepatic compromise with alanine aminotransferase (ALT) more than 3 times the ULN (a temporary swing in ALT will not result in exclusion).
  5. Other significant organ system dysfunction based on the site investigator's discretion.
  6. Severe active infections: fungal, viral, or bacterial (as confirmed by culture). Examples include tuberculosis, malaria, active hepatitis, osteomyelitis, or any other illness that would preclude the use of hydroxyurea in normal clinical practice.
  7. Active chronic leg ulcers.
  8. Known allergy to oral hydroxyurea solution or any of the excipients.
  9. Positive pregnancy test for females of child-bearing potential (in post-menarcheal females) before initiation of treatment, unless patient is sexually abstinent. Note: true abstinence is considered as being in line with the preferred and usual lifestyle of the patient. Periodic abstinence (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
  10. Inadequate contraception measures in sexually active females (in post-menarcheal females) and males of child-bearing age.
  11. Currently breastfeeding.
  12. Participating in another clinical study of an investigational medicinal product (IMP).
  13. Known infection with Human Immunodeficiency Virus.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03763656


Locations
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Jamaica
Dr Angela E Rankine- Mullings
Kingston, Jamaica
United Kingdom
Birmingham Women's and Children's NHS Foundation Trust
Birmingham, United Kingdom
Alder Hey Children's NHS Foundation Trust
Liverpool, United Kingdom
Evelina London Children's Hospital
London, United Kingdom
King's College Hospital NHS Foundation Trust
London, United Kingdom
The Royal London Children's Hospital, Barts Health NHS Trust
London, United Kingdom
Sponsors and Collaborators
Nova Laboratories Limited
Investigators
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Principal Investigator: Angela E Rankine- Mullings, MD University of the West Indies, Mona, Kingston, Jamaica
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Responsible Party: Nova Laboratories Limited
ClinicalTrials.gov Identifier: NCT03763656    
Other Study ID Numbers: INV543
2017-004568-37 ( EudraCT Number )
First Posted: December 4, 2018    Key Record Dates
Last Update Posted: February 11, 2022
Last Verified: February 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nova Laboratories Limited:
Hydroxyurea
Hydroxycarbamide
Xromi
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Thalassemia
beta-Thalassemia
Hemoglobin SC Disease
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Hydroxyurea
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors