Pharmacokinetics of Oral Hydroxyurea Solution

Sickle Cell Disease Clinical Trial

— HUPK  

Official title:

A Prospective Open Label, Pharmacokinetic Study of an Oral Hydroxyurea Solution in Children With Sickle Cell Anemia.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03763656
• Other study ID #: INV543
• Secondary ID: 2017-004568-37
• Status: Completed
• Phase: Phase 2
• Start date: November 20, 2018
• Est. completion date: December 29, 2021

Study information

• Verified date: February 2022
• Source: Nova Laboratories Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: December 29, 2021
• Est. primary completion date: May 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 17 Years

Eligibility

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 HbSߺ).

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.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• beta-Thalassemia
• Hemoglobin SC Disease
• Sickle Cell Disease
• Sickle Cell Hemoglobin C
• Sickle Cell-beta-thalassemia
• Sickle-Cell; Hemoglobin Disease, Thalassemia
• Thalassemia

Intervention

Drug:
• Hydroxyurea
Oral Hydroxyurea

Locations

Country	Name	City	State
Jamaica	Dr Angela E Rankine- Mullings	Kingston
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

Sponsors (1)

Lead Sponsor	Collaborator
Nova Laboratories Limited

Countries where clinical trial is conducted

Jamaica,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Transcranial Doppler velocity	Exploratory	Up to Week 56
Other	Urine parameters (albumin, creatinine, for urinary ACR ratio)	Exploratory	Up to Week 60
Primary	Clearance (CL/F)	Pharmacokinetic Parameters	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)
Primary	Volume of distribution (V/F)	Pharmacokinetic Parameters	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)
Primary	Time to maximum concentration (Tmax)	Pharmacokinetic Parameters	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)
Primary	Maximum plasma concentration (Cmax)	Pharmacokinetic Parameters	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)
Primary	Area under plasma concentration time curve (AUC)	Pharmacokinetic Parameters	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)
Primary	Half-life (t½)	Pharmacokinetic Parameters	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)
Secondary	Incidence of adverse events	Safety	Up to Week 64
Secondary	Absolute neutrophil count	Safety	Up to Week 60
Secondary	White Blood Cell Count and Differentials	Safety	Up to Week 60
Secondary	Platelets	Safety	Up to Week 60
Secondary	Mean Corpuscular Hemoglobin	Safety	Up to Week 60
Secondary	Hematocrit	Safety	Up to Week 60
Secondary	Bilirubin	Safety	Up to Week 60
Secondary	Elevation in liver function tests (LFTs)	Safety	Up to Week 60
Secondary	Hemoglobin/Anemia	Safety	Up to Week 60
Secondary	Clinically significant change in hematology	Safety	Up to Week 60
Secondary	Clinically significant change in biochemistry	Safety	Up to Week 60
Secondary	Clinically significant change in urinalysis	Safety	Up to Week 60
Secondary	Bacterial infections	Safety	Up to Week 60
Secondary	Viral infections	Safety	Up to Week 60
Secondary	Fungal infections	Safety	Up to Week 60
Secondary	Leg ulcers	Safety	Up to Week 60
Secondary	Fetal hemoglobin	Biomarker endpoints	Up to Week 60
Secondary	Mean Corpuscular Volume	Biomarker endpoints	Up to Week 60
Secondary	Cystatin C	Biomarker Endpoints	Up to Week 60
Secondary	Incidence of acute pain crises	Clinical status endpoints	Up to Week 60
Secondary	Number and frequency of blood transfusions	Clinical status endpoints	Up to Week 60
Secondary	Incidence of acute chest syndrome	Clinical status endpoints	Up to Week 60
Secondary	Hospitalizations	Clinical Status endpoints	Up to Week 60
Secondary	Dose escalation i.e. time to maximum tolerated dose	Clinical status endpoints	Up to Week 60
Secondary	Clinically parameters (symptoms)	Clinical status endpoints	Up to Week 60
Secondary	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	Clinical status endpoints	Up to Week 60