Antiretroviral Activity and Pharmacokinetics of Deferiprone in Healthy Volunteers and Asymptomatic HIV-infected Subjects
- Registration Number
- NCT02191657
- Lead Sponsor
- ApoPharma
- Brief Summary
The purpose of this study was to examine the safety, efficacy, and pharmacokinetics of different dosages of deferiprone in subjects with or without HIV infection.
- Detailed Description
Three cohorts were enrolled: two of individuals who were asymptomatically infected with HIV and one of healthy volunteers. Dosages were as follows:
* Cohort 1 (asymptomatic HIV infected subjects): 33 mg/kg deferiprone three times daily for a total of 99 mg/kg/day
* Cohort 2 (healthy volunteers): 50 mg/kg deferiprone three times daily for a total of 150 mg/kg/day
* Cohort 3 (asymptomatic HIV infected subjects): 50 mg/kg deferiprone three times daily for a total of 150 mg/kg/day
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 26
- Male or female aged ≥18 years and ≤ 60 years.
- Absolute neutrophil count (ANC) of >1000/mm3 for African black population and ≥ 1600/mm3 for all other races.
- For Cohort 2: HIV-negative
- For Cohorts 1 and 3: HIV-1 positive; CD4 count of at least 300/mm3; HIV-1 RNA copies (viral load) >10 000 copies/mL serum; and current physical health stable and not requiring antiretroviral treatment
- For Cohorts 1 and 3: Chest x-ray showing absence of active infectious diseases (such as tuberculosis, viral or atypical bacteria or parasitic infection).
- Presence of any severe concomitant disease.
- History of or current, recurrent or recent (4 weeks) febrile disease.
- History of opportunistic infections, neoplasm or AIDS-defining conditions.
- Inability to discontinue any medication from screening onwards, or for at least 2 weeks before the first admission; in particular any antiviral or therapy with immunosuppressive activity.
- Significant liver impairment: aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≥ 2.5 times the upper normal limit.
- Significant kidney impairment: serum creatinine ≥ two times the upper normal limit.
- Any concomitant disorder or resultant therapy likely to have interfered with subject compliance or with study procedures.
- Known hypersensitivity to any of the test materials or related compounds.
- Positive test for Hepatitis B and/or C antibodies.
- A history of multiple and/or severe allergies to drugs or foods or a history of anaphylactic reactions.
- History of seizures or epilepsy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 2 Deferiprone Subjects in this arm were healthy volunteers who received a dose of 50 mg/kg deferiprone three times a day for a total daily dosage of 150 mg/kg Cohort 3 Deferiprone Subjects in this arm were asymptomatic HIV-infected individuals who received a dose of 50 mg/kg deferiprone three times a day for a total daily dosage of 150 mg/kg. Cohort 1 Deferiprone Subjects in this arm were asymptomatic HIV-infected individuals who received a dose of 33 mg/kg deferiprone three times a day for a total daily dosage of 99 mg/kg
- Primary Outcome Measures
Name Time Method Occurrence of adverse events following repeated oral doses of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers 9 weeks (from receipt of first dose until 8 weeks after the last dose) Collection of adverse events, including abnormal findings in physical examination, vital signs, 12-lead ECG, 24-hour Holter ECG, and laboratory variables (hematology, clinical chemistry, and urinalysis)
Measurement of viral load following repeated oral doses of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers 9 weeks (pre-dose until 8 weeks after last dose) Measurement of HIV RNA load for the assessment of antiretroviral activity
Cluster of differentiation 4 (CD4) count and p24 antigen status following repeated oral doses of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers 1 week (pre-dose to day of last dose) Measurement of CD4 count and p24 antigen status for assessment of antiviral activity
- Secondary Outcome Measures
Name Time Method T1/2 of deferiprone and deferiprone 3-O-glucuronide 24-hour interval Determination of T1/2 of deferiprone and its metabolite following a dose of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers
Cmax of deferiprone and deferiprone 3-O-glucuronide 24-hour interval Determination of Cmax following a dose of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers
Tmax of deferiprone and deferiprone 3-O-glucuronide 24-hour interval Determination of Tmax of deferiprone and its metabolite following a dose of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers
Area under the curve (AUC) 0-infinity of deferiprone and deferiprone 3-O-glucuronide 24-hour interval Determination of AUC 0-infinity of deferiprone and its metabolite following a dose of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers
Trial Locations
- Locations (1)
PAREXEL International
🇿🇦Bloemfontein,, South Africa