Sickle Cell Anaemia MedDRA version: 20.0 Level: PT Classification code 10040641 Term: Sickle cell anaemia System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.0 Level: PT Classification code 10040641 Term: Sickle cell anaemia System Organ Class: 10010331 - Congenital, familial and genetic disorde
Conditions
Interventions
Product Name: Oral Hydroxycarbamide 100mg/ml Solution
Pharmaceutical Form: Oral solution
INN or Proposed INN: Hydroxycarbamide
CAS Number: 127-07-1
Sponsors
Nova Laboratories Limited
Eligibility
Sex/Gender
All
Inclusion 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 HbS0). 3. 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. Are the trial subjects under 18? yes Number of subjects for this age range: 25 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
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. Hydroxycarbamide use within 6 months before enrolment. 3. Renal insufficiency (either microalbuminuria, from spot urine or albumin/creatinine ratio [ACR value of > 0.03] and/or Proteinuria, from albumin specific dipstick) (for Proteinuria UTI will be excluded by culture/MSU). 4. Clinical evidence of hepatic compromise with ALT more than 3 times the upper limit of normal (a temporary swing in ALT will not result in exclusion). 5. Other significant organ system dysfunction based on the site investigator’s discretion. 6. Active infections: bacterial (as confirmed by culture), viral or fungal (tuberculosis, malaria, active hepatitis, osteomyelitis); 7. Active chronic leg ulcers. 8. Known allergy to oral hydroxycarbamide solution or any of the excipients. 9. Positive pregnancy test for females of child-bearing potential before initiation of treatment, unless participant is sexually abstinent. Note: true abstinence is considered as being in line with the preferred and usual lifestyle of the subject. 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 and males of child-bearing age (see section 5.12). 11. Currently breastfeeding. 12. Participating in another clinical trial of an IMP.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the absorption of oral hydroxyurea solution into the body.; Secondary Objective: To ssesss the safety of oral hydroxycarbamide solution To assess effects on laboratory parameters To assess effects on pain, transfusions, hospitalisations and acute chest syndrome To assess the acceptability and palatability (taste and smell) of oral hydroxycarbamide solution To investigate the effects of oral hydroxycarbamide solution dose escalation on laboratory and clinical parameters ; Primary end point(s): Primary Endpoints: Pharmacokinetic parameters • Clearance (CL/F) • Volume of distribution (V/F) • Time to maximum concentration (Tmax) • Maximum plasma concentration (Cmax) • Area under plasma concentration time curve (AUC) • Half-life (t1/2) ; Timepoint(s) of evaluation of this end point: Pharmacokinetics Pharmacokinetics of oral hydroxyurea solution will be evaluated at 2 study visits: Month 1: Day 1 Month 6: Day 1 On the day of sampling, hydroxyurea will be administered in the clinic. A peripheral venous catheter will be used for sampling and blood will be sampled post-dose at the following time points: Time point (h) Pre-dose 0.25 0.5 1 1.5 2 3 4 5 6 *The pre-dose sample is mandatory. At least 3 further samples (at least 2 further samples in children less than 2 years) will be collected over 0.25 to 6 hours. A single sample for pharmacokinetic analysis wil | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints: Safety: • Incidence of adverse events • Absolute neutrophil count • White cell count • Platelets • Liver function tests (LFTs) • Hemoglobin/Anemia • Additional safety laboratory parameters • Bacterial infections • Viral infections • Fungal infections • Leg ulcers Biomarkers • Fetal hemoglobin • Hemoglobin • Mean Corpuscular Volume Clinical Status • Incidence of acute pain crises* • Number and frequency of blood transfusions • Incidence of acute chest syndrome • Dose escalation i.e. time to maximum tolerated dose • Clinical parameters (symptoms) • Parent/caregiver acceptability/usability by questionnaire Palatability and Acceptability: Evaluate the taste acceptability of the new oral liquid formulation of hydroxyurea. Exploratory Endpoints: • Transcranial Doppler (TCD) velocity • Urine parameters (albumin, creatinine for ACR ratio) ;Timepoint(s) of evaluation of this end point: Secondary endpoints will be assessed at each study visit as appropriate | — |
Countries
Jamaica, United Kingdom
Contacts
Public ContactHead of Clinical Development
Nova Laboratories Limited
Outcome results
None listed