HIV/AIDS Cryptococcal Meningitis
Conditions
Interventions
Immediate release flucytosine formulation
Sustained release flucytosine formulation
Sponsors
Drug for Neglected Diseases initiative
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male and female = 18 yrs with a first episode of cryptococcal meningitis (CSF India ink or CSF positive CrAg test) • Serologically confirmed HIV infection at the point of trial screening or at any time prior • Willing to participate in the trial. Consent will be obtained from the family/guardians/person with legal responsibility for participants who lack capacity to consent and from the participants themselves after recovery. • Glasgow Coma Scale (GCS) assessed as 15/15. Following the safety review and DMC recommendation, participants will be allowed with GCS >10./15
Exclusion criteria
Exclusion criteria: • Pregnant (confirmed by a highly sensitive urinary pregnancy test) or breastfeeding. • Women of childbearing potential who do not agree to use contraception during trial period. • Male participants (or their female partners of childbearing potential) who do not agree to use effective contraception during trial • Known dihydropyridine dehydrogenase (DPD) deficiency • Already taking systemic antifungal treatment for > 48 hours • Participants 3x upper limit of normal) on baseline blood testing • Participants should be excluded in case of any severe medical or psychiatric condition
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary PK parameter for IR and SR 5FC: Area-under-curve for 5FC plasma concentration versus time, from time zero to t, where t is the time of the last quantifiable concentration (AUC(0-t));Early fungicidal activity (EFA) defined by cryptococcus clearance in the cerebrospinal fluid (CSF) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary PK parameters for IR and SR 5FC: - Maximum observed plasma concentration (Cmax) and Cmax at steady-state (Cmax,ss); - Time to maximum observed plasma concentration (tmax); - Minimum observed plasma concentration (Cmin) and Cmin at steady-state (Cmin,ss); - Area under the plasma concentration versus time curve, with extrapolation to infinity (AUC(0 8)); - Average concentration during a dosing interval (AUC(0- t) / t)(Cav) - Fluctuation ([(Cmax-Cmin)/Cav]) - Terminal elimination rate constant (?z); - Apparent terminal elimination half-life (t½); - Time over antibiotic concentration that would inhibit the growth of 90% of Cryptococcus neoformans (MIC90) ;Safety endpoints for IR and SR 5FC - Treatment Emergent Adverse Events (TEAEs) (clinical, laboratory and ECG) - Treatment Emergent Serious Adverse Events (TESAEs) (clinical, laboratory and ECG) - Grade III, IV and V TEAEs and TESAEs - Treatment discontinuation due to Adverse events (AEs) | — |
Countries
Malawi, Tanzania
Contacts
Public ContactNabila Ibnou Zekri Lassout
Senior Clinical Project Manager Drug for Neglected Diseases initiative
Outcome results
None listed