Phase 2
Completed N=33
Pharmacokinetics of Oral Hydroxyurea Solution
Sickle Cell Disease · Sickle-Cell; Hemoglobin Disease, Thalassemia · Sickle Cell-beta-thalassemia · Sickle Cell Hemoglobin C
Source: ClinicalTrials.gov NCT03763656 ↗
Enrolled (actual)
33
Serious AEs
18.8%
Results posted
Oct 2024
Primary outcomePrimary: Clearance (CL/F) — 3.61 L/hr
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Clearance (CL/F) |
3.61 | — |
| PRIMARY Volume of Distribution (V/F) |
11.4 | — |
| PRIMARY Time to Maximum Concentration (Tmax) |
1.253; 1.265; 1.238; 1.269 | — |
| PRIMARY Maximum Plasma Concentration Cmax (ug/mL) |
13.124; 12.807; 13.068; 13.404 | — |
| PRIMARY Area Under Plasma Concentration Time Curve (AUC 0-Inf) |
64.721; 62.537; 62.899; 68.948 | — |
| PRIMARY Terminal Half-life (Hours) |
3.880; 4.107; 3.949; 3.634 | — |
| SECONDARY Adverse Events |
339; 339; 7; 19; 28; 53 | — |
| SECONDARY Absolute Neutrophil Count (ANC) |
4.90; 4.30; 5.38; 4.43; 2.70; 2.27 | — |
| SECONDARY White Blood Cell Count (Leukocytes) |
13.01; 12.24; 14.59; 10.88; 7.48; 7.90 | — |
| SECONDARY Platelets |
409.06; 383.80; 381.31; 466.10; 315.10; 333.67 | — |
| SECONDARY Mean Corpuscular Hemoglobin (MCH) |
27.57; 23.80; 28.36; 28.53; 33.36; 28.95 | — |
| SECONDARY Hematocrit |
25.02; 30.60; 23.24; 24.30; 27.74; 30.38 | — |
| SECONDARY Bilirubin |
37.43; 14.78; 39.60; 47.53; 26.12; 7.42 | — |
| SECONDARY Elevation in Liver Function Tests (LFTs) |
3.55; 4.19; 3.60; 3.10; 3.57; 4.06 | — |
| SECONDARY Hemoglobin |
8.32; 9.76; 8.07; 7.99; 9.47; 10.60 | — |
| SECONDARY Bacterial Infections |
7; 0; 3; 4; 17; 1 | — |
| SECONDARY Viral Infections |
8; 0; 8; 0; 23; 4 | — |
| SECONDARY Fungal Infections |
1; 0; 0; 1; 4; 1 | — |
| SECONDARY Leg Ulcers |
0; 0; 0; 0; 1; 0 | — |
| SECONDARY Fetal Hemoglobin |
11.90; 21.52; 10.94; 5.57; 23.53; 26.32 | — |
| SECONDARY Mean Corpuscular Volume (MCV) |
83.13; 76.42; 83.25; 86.30; 97.64; 81.68 | — |
| SECONDARY Cystatin C |
7.52; 8.89; 6.87; 7.18; 7.50; 8.36 | — |
| SECONDARY Incidence of Acute Vaso-Occlusive Pain Crises (VOC) |
0.5; 0.0; 0.7; 0.6; 0.2; 0.3 | — |
| SECONDARY Number and Frequency of Blood Transfusions |
30; 21; 9 | — |
| SECONDARY Acute Chest Syndrome (ACS) |
0.5; 0.00; 0.6; 0.7; 0.2; 0.00 | — |
| SECONDARY Hospitalizations |
1.7; 0.3; 2.0; 1.9; 0.3; 0.3 | — |
| SECONDARY Dose Escalation i.e. Maximum Tolerated Dose (MTD) |
25.63; 23.50; 26.11; 26.67 | — |
| SECONDARY Other SCA-related Hospitalizations |
0.4; 0.3; 0.4; 0.4; 0.0; 0.00 | — |
| SECONDARY Parent/Caregiver Palatability and Acceptability Questionnaire |
84.2; 71.3; 91.1; 80.8; 83.8; 74.8 | — |
| SECONDARY Vitamin D |
59.35; 83.07; 65.43; 35.39; 62.26; 86.44 | — |
| SECONDARY Other Non-SCA-related Hospitalizations |
0.2; 0.00; 0.3; 0.2; 0.00; 0.00 | — |
Eligibility Criteria
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 have compromised the safety of the patient or which might have interfered 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 μmol/L]).
- Clinical evidence of hepatic compromise with alanine aminotransferase (ALT) >3 times the ULN (a temporary swing in ALT did not result in exclusion).
- Other significant organ system dysfunction based on the site Investigators discretion.
- 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.
- Active chronic leg ulcers.
- Known allergy to oral HU solution or any of the excipients.
- 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.
- Inadequate contraception measures in sexually active females (post-menarcheal females) and males of child-bearing age (see Section 9.5.1.10.4).
- Breastfeeding at study initiation.
- Participation in another clinical trial of an IMP.
- Known infection with HIV.
Data sourced from ClinicalTrials.gov (NCT03763656). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.