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

HIV Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02191657
• Other study ID #: LA26-106
• Status: Completed
• Phase: Phase 1
• First received: July 14, 2014
• Last updated: July 14, 2014
• Start date: November 2006
• Est. completion date: April 2010

Study information

• Verified date: November 2007
• Source: ApoPharma
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Africa: Medicines Control Council
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: April 2010
• Est. primary completion date: May 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• HIV Infection

Intervention

Drug:
• Deferiprone
Oral iron chelator

Locations

Country	Name	City	State
South Africa	PAREXEL International	Bloemfontein,

Sponsors (1)

Lead Sponsor	Collaborator
ApoPharma

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Yes
Primary	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)	No
Primary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No