Back to results

Pharmacokinetics of Oral Hydroxyurea Solution (HUPK)

Primary Purpose

Sickle Cell Disease, Sickle-Cell; Hemoglobin Disease, Thalassemia, Sickle Cell-beta-thalassemia

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Hydroxyurea

About this trial

This is an interventional treatment trial for Sickle Cell Disease focused on measuring Hydroxyurea, Hydroxycarbamide, Xromi

Eligibility Criteria

6 Months - 17 Years (Child)All SexesDoes not accept 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.

Sites / Locations

Dr Angela E Rankine- Mullings
Birmingham Women's and Children's NHS Foundation Trust
Alder Hey Children's NHS Foundation Trust
Evelina London Children's Hospital
King's College Hospital NHS Foundation Trust
The Royal London Children's Hospital, Barts Health NHS Trust

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Open Label

Arm Description

Novel oral solution formulation of hydroxyurea

Outcomes

Primary Outcome Measures

Clearance (CL/F)

Pharmacokinetic Parameters

Volume of distribution (V/F)

Pharmacokinetic Parameters

Time to maximum concentration (Tmax)

Pharmacokinetic Parameters

Maximum plasma concentration (Cmax)

Pharmacokinetic Parameters

Area under plasma concentration time curve (AUC)

Pharmacokinetic Parameters

Half-life (t½)

Pharmacokinetic Parameters

Secondary Outcome Measures

Incidence of adverse events

Safety

Absolute neutrophil count

Safety

White Blood Cell Count and Differentials

Safety

Platelets

Safety

Mean Corpuscular Hemoglobin

Safety

Hematocrit

Safety

Bilirubin

Safety

Elevation in liver function tests (LFTs)

Safety

Hemoglobin/Anemia

Safety

Clinically significant change in hematology

Safety

Clinically significant change in biochemistry

Safety

Clinically significant change in urinalysis

Safety

Bacterial infections

Safety

Viral infections

Safety

Fungal infections

Safety

Leg ulcers

Safety

Fetal hemoglobin

Biomarker endpoints

Mean Corpuscular Volume

Biomarker endpoints

Cystatin C

Biomarker Endpoints

Incidence of acute pain crises

Clinical status endpoints

Number and frequency of blood transfusions

Clinical status endpoints

Incidence of acute chest syndrome

Clinical status endpoints

Hospitalizations

Clinical Status endpoints

Dose escalation i.e. time to maximum tolerated dose

Clinical status endpoints

Clinically parameters (symptoms)

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

Clinical status endpoints

Full Information

NCT ID

NCT03763656

First Posted

December 3, 2018

Last Updated

February 10, 2022

Sponsor

Nova Laboratories Limited

1. Study Identification

Unique Protocol Identification Number

NCT03763656

Brief Title

Pharmacokinetics of Oral Hydroxyurea Solution

Acronym

HUPK

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Completed

Study Start Date

November 20, 2018 (Actual)

Primary Completion Date

May 19, 2021 (Actual)

Study Completion Date

December 29, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Nova Laboratories Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sickle Cell Disease, Sickle-Cell; Hemoglobin Disease, Thalassemia, Sickle Cell-beta-thalassemia, Sickle Cell Hemoglobin C

Keywords

Hydroxyurea, Hydroxycarbamide, Xromi

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

33 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Open Label

Arm Type

Experimental

Arm Description

Novel oral solution formulation of hydroxyurea

Intervention Type

Drug

Intervention Name(s)

Hydroxyurea

Intervention Description

Oral Hydroxyurea

Primary Outcome Measure Information:

Title

Clearance (CL/F)

Description

Pharmacokinetic Parameters

Time Frame