Sickle Cell DiseasePHOENIX-NGNCT07543289
Hydroxyurea Optimisation in Sickle Cell Disease
An observational study of Sickle Cell Disease, run by Ochuko Orherhe at 1 site in Nigeria.
Trial summary
The wide interindividual variability in clinical response to hydroxyurea therapy in the management of sickle cell disease has limited its use. These variabilities have been linked to differences in pharmacodynamics, pharmacokinetics, and pharmacogenetics. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Hydroxyurea (HU)
- How many people
- 100 participants
- Where
- 1 siteNigeria
- Study dates
- 8 May 2026to Oct 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study population for this research comprises patients diagnosed with sickle cell disease (SCD) of Nigerian descent, recruited from selected clinical centres within Nigeria ( Sickle Cell Foundation, Ibadan and the Obafemi Awolowo University Teaching Hospital Complex). They will be consented SCD adult patients who have been on hydroxyurea at least six months before study commencement or who are willing to commence hydroxyurea therapy. In both instances, they will be SCD patients whose genetic profile for the major metabolising enzymes are known.
Who may be able to join
- Patients with confirmed diagnosis of sickle cell disease (SCD) (e.g., HbSS, HbSC) and of Nigerian descent.
- Patients currently on hydroxyurea therapy or hydroxyurea-naive patients who are willing to commence hydroxyurea therapy.
- Patients whose genotypic profile for the major metabolising enzymes has been previously done e.g. CYP2D6.
- Patients who consent to be part of the study
Who cannot join
- Patients with severe comorbidities that may significantly alter pharmacokinetics (e.g., advanced renal or hepatic failure)
- Patients in acute crisis at the time of sampling.
- Patients with documented poor adherence to other medications previously on.
- Pregnant females and lactating mothers.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Nigeria1 site, 1 recruiting
- Recruiting
Obafemi Awolowo University Teaching Hospital Complex
Ile-Ife, Osun State, 220282
Olusola J Olarewaju, +2348030698673, olarewajuolusolajoseph@gmail.com
Rahman Bolarinwa, +2348037115854, rbolarin@oauife.edu.ng
About this study
Official title: Pharmacogenetics and Model-Informed Optimisation of Hydroxyurea Therapy in Sickle Cell Disease Patients of Nigerian Descent
The wide interindividual variability in clinical response to hydroxyurea therapy in the management of sickle cell disease has limited its use. These variabilities have been linked to differences in pharmacodynamics, pharmacokinetics, and pharmacogenetics. This study, therefore, aims to enhance understanding of these factors as they relate to hydroxyurea therapy, with the overall goal of developing a precision medicine algorithm.
The study will be a prospective cohort pharmacokinetic study of 100 Nigerian patients with sickle cell disease, including current hydroxyurea users and naive patients. Pharmacodynamic markers will be collected to evaluate response. PopPK and PK-PD models will be developed in Monolix, exposure-response relationships will be analysed in R, and pregnancy, lactation, and paediatrics PBPK models will be developed in Simcyp or PK-SIM to inform dose optimisation.
Read more
This study aims to build a pharmacometric model by integrating differences in pharmacokinetics, pharmacodynamics, and pharmacogenetics of hydroxyurea, which could aid the optimisation of hydroxyurea for sickle cell patients in Nigeria.
The objectives of the study are i. To determine the prevalence of genetic polymorphisms in metabolic enzymes and transporters relevant to the disposition of hydroxyurea in the Nigerian sickle cell disease population, ii. To develop and validate an analytical method for the quantification of hydroxyurea using high-performance liquid chromatography.
iii. To evaluate the influence of genetic and other covariates on hydroxyurea disposition in the Nigerian sickle cell disease population using population pharmacokinetic modelling, iv. To investigate the relationship between hydroxyurea exposure and clinical outcomes (foetal haemoglobin, mean corpuscular volume, reduction in vaso-occlusive crises (VOC), and improved blood count) using pharmacokinetic-pharmacodynamic modelling, v. To develop physiologically-based pharmacokinetic (PBPK) models that could predict hydroxyurea concentrations in special populations of sickle cell disease patients in Nigeria i.e. pregnant women, lactating mothers, breastfed infants, and paediatrics.
vi. To develop a dosing guideline for hydroxyurea therapy in Nigerian sickle cell patients.
Overall, this study will provide scientific knowledge that can enhance clinical decision-making in sickle cell management within the Nigerian population, and the models could serve as a template to optimize hydroxyurea use in this population.
- Conditions
- Sickle Cell Disease
- Being tested
- Hydroxyurea (HU)
- Keywords
- Modelling, Genetic Polymorphism, Pharmacokinetics, Clinical Outcomes, Hydroxyurea, Pharmacogenetics
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydroxyurea (HU)Drug
All study participants are sickle cell disease patients who are currently on hydroxyurea therapy or who would be willing to commence hydroxyurea therapy.
What is being measured
The primary outcome is the main question the study is designed to answer.
Increase in foetal haemoglobin
Hydroxyurea exerts its therapeutic effects primarily through the induction of foetal haemoglobin production, thereby inhibiting the polymerization of sickled haemoglobin and ameliorating the pathophysiological sequelae of sickle cell disease. By inhibiting ribonucleotide reductase, hydroxyurea interferes with DNA synthesis, prompting the differentiation of erythroid progenitors into red cells containing elevated levels of foetal haemoglobin.
Measured: 6 months
Secondary outcomes (1)
Reduction in frequency of vaso-occlusive crises
The phenotypic expression of the increase in foetal haemoglobin is the overall reduction of the incidences of painful crises due to vaso-occlusion, acute chest syndrome, hospitalizations, and blood transfusions, consequently reducing hospitalisations and morbidity
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2026
- Study start8 May 2026
- Primary completion30 Apr 2027 (estimated)
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ochuko Orherhe
- Sponsor type
- University, hospital or other
- Collaborators
- Consortium for Advanced Research Training in Africa (CARTA), Obafemi Awolowo University, Obafemi Awolowo University Teaching Hospital
- Responsible party
- Sponsor-investigator, Ochuko Orherhe, Obafemi Awolowo University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07543289
- Sponsor's protocol ID
- ERC/2024/07/12
- Acronym
- PHOENIX-NG
- Status last verified
- Oct 2026
- First submitted
- 15 Apr 2026
- Last updated
- 27 Oct 2026
- Results posted
- No
- Individual data sharing
- No: Each study participant will be assigned a study ID. The hard copies of data collection materials will use the study ID only as identifiers and not the personal identifying information. The code linking the data to the patient's personal information will only be available to the me, the principal investigator. However, in the event that a discovery is made in a study particpant that requires medical attention, the attending physician (who are the facility contacts and patients' medical doctors) will be communicated and individual participant data shared with them.
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacogenetics and Model-Informed Optimisation of Hydroxyurea Therapy in Sickle Cell Disease Patients of Nigerian Descent
- ClinicalTrials.gov ID
- NCT07543289
- Acronym / sponsor ID
- PHOENIX-NG / ERC/2024/07/12
- Conditions
- Sickle Cell Disease
- Keywords
- Modelling, Genetic Polymorphism, Pharmacokinetics, Clinical Outcomes, Hydroxyurea, Pharmacogenetics
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Ochuko OrherheUniversity, hospital or other
- Collaborators
- Consortium for Advanced Research Training in Africa (CARTA), Obafemi Awolowo University, Obafemi Awolowo University Teaching Hospital
- Study start
- 8 May 2026 (actual)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- Oct 2027 (estimated)
- First posted
- 21 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The wide interindividual variability in clinical response to hydroxyurea therapy in the management of sickle cell disease has limited its use. These variabilities have been linked to differences in pharmacodynamics, pharmacokinetics, and pharmacogenetics. This study, therefore, aims to enhance understanding of these factors as they relate to hydroxyurea therapy, with the overall goal of developing a precision medicine algorithm.
The study will be a prospective cohort pharmacokinetic study of 100 Nigerian patients with sickle cell disease, including current hydroxyurea users and naive patients. Pharmacodynamic markers will be collected to evaluate response. PopPK and PK-PD models will be developed in Monolix, exposure-response relationships will be analysed in R, and pregnancy, lactation, and paediatrics PBPK models will be developed in Simcyp or PK-SIM to inform dose optimisation.
This study aims to build a pharmacometric model by integrating differences in pharmacokinetics, pharmacodynamics, and pharmacogenetics of hydroxyurea, which could aid the optimisation of hydroxyurea for sickle cell patients in Nigeria.
The objectives of the study are i. To determine the prevalence of genetic polymorphisms in metabolic enzymes and transporters relevant to the disposition of hydroxyurea in the Nigerian sickle cell disease population, ii. To develop and validate an analytical method for the quantification of hydroxyurea using high-performance liquid chromatography.
iii. To evaluate the influence of genetic and other covariates on hydroxyurea disposition in the Nigerian sickle cell disease population using population pharmacokinetic modelling, iv. To investigate the relationship between hydroxyurea exposure and clinical outcomes (foetal haemoglobin, mean corpuscular volume, reduction in vaso-occlusive crises (VOC), and improved blood count) using pharmacokinetic-pharmacodynamic modelling, v. To develop physiologically-based pharmacokinetic (PBPK) models that could predict hydroxyurea concentrations in special populations of sickle cell disease patients in Nigeria i.e. pregnant women, lactating mothers, breastfed infants, and paediatrics.
vi. To develop a dosing guideline for hydroxyurea therapy in Nigerian sickle cell patients.
Overall, this study will provide scientific knowledge that can enhance clinical decision-making in sickle cell management within the Nigerian population, and the models could serve as a template to optimize hydroxyurea use in this population.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population for this research comprises patients diagnosed with sickle cell disease (SCD) of Nigerian descent, recruited from selected clinical centres within Nigeria ( Sickle Cell Foundation, Ibadan and the Obafemi Awolowo University Teaching Hospital Complex). They will be consented SCD adult patients who have been on hydroxyurea at least six months before study commencement or who are willing to commence hydroxyurea therapy. In both instances, they will be SCD patients whose genetic profile for the major metabolising enzymes are known.
Key inclusion criteria (4 listed)
- Patients with confirmed diagnosis of sickle cell disease (SCD) (e.g., HbSS, HbSC) and of Nigerian descent.
- Patients currently on hydroxyurea therapy or hydroxyurea-naive patients who are willing to commence hydroxyurea therapy.
- Patients whose genotypic profile for the major metabolising enzymes has been previously done e.g. CYP2D6.
- Patients who consent to be part of the study
Key exclusion criteria (4 listed)
- Patients with severe comorbidities that may significantly alter pharmacokinetics (e.g., advanced renal or hepatic failure)
- Patients in acute crisis at the time of sampling.
- Patients with documented poor adherence to other medications previously on.
- Pregnant females and lactating mothers.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydroxyurea (HU)All study participants are sickle cell disease patients who are currently on hydroxyurea therapy or who would be willing to commence hydroxyurea therapy. | Drug | – |
Primary outcome
Increase in foetal haemoglobin
Time frame: 6 months
Hydroxyurea exerts its therapeutic effects primarily through the induction of foetal haemoglobin production, thereby inhibiting the polymerization of sickled haemoglobin and ameliorating the pathophysiological sequelae of sickle cell disease. By inhibiting ribonucleotide reductase, hydroxyurea interferes with DNA synthesis, prompting the differentiation of erythroid progenitors into red cells containing elevated levels of foetal haemoglobin.
1 secondary outcome
Reduction in frequency of vaso-occlusive crises
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2026.
- Individual participant dataSharing planned: No. Each study participant will be assigned a study ID. The hard copies of data collection materials will use the study ID only as identifiers and not the personal identifying information. The code linking the data to the patient's personal information will only be available to the me, the principal investigator. However, in the event that a discovery is made in a study particpant that requires medical attention, the attending physician (who are the facility contacts and patients' medical doctors) will be communicated and individual participant data shared with them.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sickle Cell Disease, run by Ochuko Orherhe at 1 site in Nigeria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Nigeria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ochuko M. Orherhe, M.Phil. (+2348051589453, oorherhe@oauife.edu.ng), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Increase in foetal haemoglobin (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.