HUPK: Pharmacokinetics of Oral Hydroxyurea Solution

Sponsor

Nova Laboratories Limited (Industry)

Overall Status

Completed

CT.gov ID

NCT03763656

Collaborator

(none)

Enrollment

Locations

Arm

37.3

Actual Duration (Months)

5.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

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 :

Nov 20, 2018

Actual Primary Completion Date :

May 19, 2021

Actual Study Completion Date :

Dec 29, 2021

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Open Label

Novel oral solution formulation of hydroxyurea

Drug: Hydroxyurea

Oral Hydroxyurea

Outcome Measures

Primary Outcome Measures

Clearance (CL/F) [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
Volume of distribution (V/F) [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
Time to maximum concentration (Tmax) [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
Maximum plasma concentration (Cmax) [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
Area under plasma concentration time curve (AUC) [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
Half-life (t½) [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

Incidence of adverse events [Up to Week 64]
Safety
Absolute neutrophil count [Up to Week 60]
Safety
White Blood Cell Count and Differentials [Up to Week 60]
Safety
Platelets [Up to Week 60]
Safety
Mean Corpuscular Hemoglobin [Up to Week 60]
Safety
Hematocrit [Up to Week 60]
Safety
Bilirubin [Up to Week 60]
Safety
Elevation in liver function tests (LFTs) [Up to Week 60]
Safety
Hemoglobin/Anemia [Up to Week 60]
Safety
Clinically significant change in hematology [Up to Week 60]
Safety
Clinically significant change in biochemistry [Up to Week 60]
Safety
Clinically significant change in urinalysis [Up to Week 60]
Safety
Bacterial infections [Up to Week 60]
Safety
Viral infections [Up to Week 60]
Safety
Fungal infections [Up to Week 60]
Safety
Leg ulcers [Up to Week 60]
Safety
Fetal hemoglobin [Up to Week 60]
Biomarker endpoints
Mean Corpuscular Volume [Up to Week 60]
Biomarker endpoints
Cystatin C [Up to Week 60]
Biomarker Endpoints
Incidence of acute pain crises [Up to Week 60]
Clinical status endpoints
Number and frequency of blood transfusions [Up to Week 60]
Clinical status endpoints
Incidence of acute chest syndrome [Up to Week 60]
Clinical status endpoints
Hospitalizations [Up to Week 60]
Clinical Status endpoints
Dose escalation i.e. time to maximum tolerated dose [Up to Week 60]
Clinical status endpoints
Clinically parameters (symptoms) [Up to Week 60]
Clinical status endpoints
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 [Up to Week 60]
Clinical status endpoints

Other Outcome Measures

Transcranial Doppler velocity [Up to Week 56]
Exploratory
Urine parameters (albumin, creatinine, for urinary ACR ratio) [Up to Week 60]
Exploratory

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female aged from 6 months to 17.99 years of age (i.e. to the day before 18th birthday).
Diagnosis of sickle cell anemia (HbSS and HbSβº).
Parent(s)/legal guardian able and willing to provide written informed consent for the child to take part in the study.
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:

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.
Hydroxyurea use within 6 months before enrolment.
Renal insufficiency (known creatinine more than twice the upper limit of normal (ULN) for age and > 1.0 mg/dL [88.4 micromol/L])
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).
Other significant organ system dysfunction based on the site investigator's discretion.
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.
Active chronic leg ulcers.
Known allergy to oral hydroxyurea solution or any of the excipients.
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.
Inadequate contraception measures in sexually active females (in post-menarcheal females) and males of child-bearing age.
Currently breastfeeding.
Participating in another clinical study of an investigational medicinal product (IMP).
Known infection with Human Immunodeficiency Virus.

Contacts and Locations

Locations

	Site	City	Country
1	Dr Angela E Rankine- Mullings	Kingston	Jamaica
2	Birmingham Women's and Children's NHS Foundation Trust	Birmingham	United Kingdom
3	Alder Hey Children's NHS Foundation Trust	Liverpool	United Kingdom
4	Evelina London Children's Hospital	London	United Kingdom
5	King's College Hospital NHS Foundation Trust	London	United Kingdom
6	The Royal London Children's Hospital, Barts Health NHS Trust	London	United Kingdom