Antiretroviral Activity and Pharmacokinetics of Deferiprone in Healthy Volunteers and Asymptomatic HIV-infected Subjects

Study Overview
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Brief Summary
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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
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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

Official Title
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A Double Blind, Placebo-controlled, Dose-escalating, Multiple Dose Study, Investigating the Safety, Antiretroviral Activity, Tolerability and Pharmacokinetic Profile of Deferiprone When Administered in Healthy Volunteers and Asymptomatic HIV Infected Subjects

Conditions
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HIV Infection

Intervention / Treatment
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* Drug: Deferiprone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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). Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>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 | Drug: Deferiprone<br>* Oral iron chelator<br>* Other names: L1;|
| Experimental: Cohort 2<br>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 | Drug: Deferiprone<br>* Oral iron chelator<br>* Other names: L1;|
| Experimental: Cohort 3<br>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. | Drug: Deferiprone<br>* Oral iron chelator<br>* Other names: L1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of adverse events following repeated oral doses of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers | 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) | 9 weeks (from receipt of first dose until 8 weeks after the last dose) | 
| Measurement of viral load following repeated oral doses of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers | Measurement of HIV RNA load for the assessment of antiretroviral activity | 9 weeks (pre-dose until 8 weeks after last dose) | 
| Cluster of differentiation 4 (CD4) count and p24 antigen status following repeated oral doses of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers | Measurement of CD4 count and p24 antigen status for assessment of antiviral activity | 1 week (pre-dose to day of last dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of deferiprone and deferiprone 3-O-glucuronide | Determination of Cmax following a dose of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers | 24-hour interval | 
| Tmax of deferiprone and deferiprone 3-O-glucuronide | Determination of Tmax of deferiprone and its metabolite following a dose of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers | 24-hour interval | 
| Area under the curve (AUC) 0-infinity of deferiprone and deferiprone 3-O-glucuronide | Determination of AUC 0-infinity of deferiprone and its metabolite following a dose of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers | 24-hour interval | 
| T1/2 of deferiprone and deferiprone 3-O-glucuronide | Determination of T1/2 of deferiprone and its metabolite following a dose of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers | 24-hour interval | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, deferiprone, iron chelation