Clinical trial NCT02191657: Antiretroviral Activity and Pharmacokinetics of Deferiprone in Healthy Volunteers and Asymptomatic HIV-infected Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infection
Keywords: HIV
deferiprone
iron chelation
Lead sponsor: ApoPharma
Sponsor class: INDUSTRY
First posted: 2014-07-16
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

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

Eligibility criteria: 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.

Primary outcomes:
measure: Occurrence of adverse events following repeated oral doses of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers
timeFrame: 9 weeks (from receipt of first dose until 8 weeks after the last dose)
measure: Measurement of viral load following repeated oral doses of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers
timeFrame: 9 weeks (pre-dose until 8 weeks after last dose)
measure: Cluster of differentiation 4 (CD4) count and p24 antigen status following repeated oral doses of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers
timeFrame: 1 week (pre-dose to day of last dose)
Secondary outcomes:
measure: Cmax of deferiprone and deferiprone 3-O-glucuronide
timeFrame: 24-hour interval
measure: Tmax of deferiprone and deferiprone 3-O-glucuronide
timeFrame: 24-hour interval
measure: Area under the curve (AUC) 0-infinity of deferiprone and deferiprone 3-O-glucuronide
timeFrame: 24-hour interval
measure: T1/2 of deferiprone and deferiprone 3-O-glucuronide
timeFrame: 24-hour interval
Other outcomes:
Locations:
city: Bloemfontein,
country: South Africa
facility: PAREXEL International
Study officials:
affiliation: University of the Free State, South Africa
name: Dewald Steyn, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Saxena D, Spino M, Tricta F, Connelly J, Cracchiolo BM, Hanauske AR, D'Alliessi Gandolfi D, Mathews MB, Karn J, Holland B, Park MH, Pe'ery T, Palumbo PE, Hanauske-Abel HM. Drug-Based Lead Discovery: The Novel Ablative Antiretroviral Profile of Deferiprone in HIV-1-Infected Cells and in HIV-Infected Treatment-Naive Subjects of a Double-Blind, Placebo-Controlled, Randomized Exploratory Trial. PLoS One. 2016 May 18;11(5):e0154842. doi: 10.1371/journal.pone.0154842. eCollection 2016.