Pharmacokinetics of Oral Hydroxyurea Solution (HUPK)

Nova Laboratories

Status and phase: Completed; Phase 2; Phase 1

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

Treatments: Drug: Oral Hydroxyurea (100 mg/mL) Solution

Study type: Interventional

Funder types: Industry

Identifiers

NCT03763656

2017-004568-37 (EudraCT Number)

INV543

Details and patient eligibility

About

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.

Enrollment: 33 patients

Sex: All

Ages: 6 months to 17 years old

Volunteers: No Healthy Volunteers

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 have compromised the safety of the patient or which might have interfered 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 μmol/L]).
4. Clinical evidence of hepatic compromise with alanine aminotransferase (ALT) >3 times the ULN (a temporary swing in ALT did not result in exclusion).
5. Other significant organ system dysfunction based on the site Investigators discretion.
6. Severe active infections: fungal, viral or bacterial (as confirmed by culture), examples included tuberculosis, malaria, active hepatitis, osteomyelitis or any other illness that would have precluded the use of HU in normal clinical practice.
7. Active chronic leg ulcers.
8. Known allergy to oral HU 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 participant was sexually abstinent. Note: True abstinence was considered as being in line with the preferred and usual lifestyle of the participant. 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 (post-menarcheal females) and males of child-bearing age (see Section 9.5.1.10.4).
11. Breastfeeding at study initiation.
12. Participation in another clinical trial of an IMP.
13. Known infection with HIV.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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33 participants in 1 patient group

Open Label

Experimental group

Description:

Novel oral solution formulation of hydroxyurea

Treatment:

Drug: Oral Hydroxyurea (100 mg/mL) Solution