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

NCT02191657 | Completed Phase 1 DMC

• 1 other identifier: LA26-106
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Infection

Keywords

HIV; deferiprone; iron chelation

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• Cmax of deferiprone and deferiprone 3-O-glucuronide

  24-hour interval

• Tmax of deferiprone and deferiprone 3-O-glucuronide

  24-hour interval

• Area under the curve (AUC) 0-infinity of deferiprone and deferiprone 3-O-glucuronide

  24-hour interval

• T1/2 of deferiprone and deferiprone 3-O-glucuronide

  24-hour interval

Study Arms (3)

Cohort 1

EXPERIMENTAL

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

Cohort 2

EXPERIMENTAL

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

Cohort 3

EXPERIMENTAL

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

Interventions

Deferiprone DRUG

Oral iron chelator

Also known as: Ferriprox, L1

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• ApoPharma: lead

Study Sites (1)

PAREXEL International

Bloemfontein, 9324, South Africa

Location

Related Publications (1)

• 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.

  PMID: 27191165 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Deferiprone; Long Interspersed Nucleotide Elements

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyridones; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Retroelements; Interspersed Repetitive Sequences; Repetitive Sequences, Nucleic Acid; Base Sequence; Molecular Structure; Biochemical Phenomena; Chemical Phenomena; Genetic Structures; Genetic Phenomena; Genome Components; Genome

Study Officials

• Dewald Steyn, MD

  University of the Free State, South Africa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2014
• First Posted: July 16, 2014
• Study Start: November 1, 2006
• Primary Completion: May 1, 2008
• Study Completion: April 1, 2010
• Last Updated: July 16, 2014

Record last verified: 2007-11

Locations

ZA (1)