Atazanavir Used in Combination With Other Anti-HIV Drugs in HIV-Infected Infants, Children, and Adolescents

• Status: Completed
• Trial end date: 2014-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study was to find a safe and tolerable dose of the protease inhibitor (PI) atazanavir (ATV), with or without a low-dose boost of the PI ritonavir (RTV), when taken with other anti-HIV drugs in HIV infected infants, children, and adolescents.

Advancements in anti-HIV drugs for HIV infected children and adolescents have been hard to make, in part because these patients often do not take the drugs as prescribed. ATV may be a better option because it is available in the form of powder which children and adolescents may be more willing to take regularly. Using a low dose of RTV as a boosting agent for ATV may also increase the chances of virologic response of highly active antiretroviral treatment (HAART)-experienced patients. This study aimed to find safe and tolerable doses of ATV with or without low-dose RTV boost in infants, children, and adolescents. For this study, participants were enrolled in the United States and South Africa.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); International Maternal Pediatric Adolescent AIDS Clinical Trials Group
• Treatments: Atazanavir Sulfate; HIV Protease Inhibitors; Protease Inhibitors; Ritonavir

Criteria

Inclusion Criteria for Step I:

• Age: 91 days to 21 years of age (not including the 22nd birthday).

• A confirmed diagnosis of HIV infection defined by the current definition of the IMPAACT Virology Core Laboratory Committee. More information about this criterion can be found in the protocol.

• Viral load greater than or equal to 5,000 copies/mL

• Any CDC clinical classification and immune status

• Antiretroviral treatment-naïve or -experienced study candidates must be able to add two new NRTIs as part of their new therapy in this protocol, or have genotypic evidence of sensitivity to two NRTIs (the NRTIs must be used in combinations recommended in the Guidelines for the Use of Antiretroviral Agents in Pediatric and Adolescent HIV Infection). More information about this criterion can be found in the protocol.

• Study candidates must show evidence of retained phenotypic sensitivity to ATV (resistance index ratio of less than 10) when the subject has failed (after at least 12 weeks of therapy) two or more courses of PI containing regimens. More information about this criterion can be found in the protocol.

• Demonstrated ability and willingness to swallow study medications

• Study candidate, parent, or legal guardian must be able and willing to provide signed informed consent

• Female participants who are sexually active and able to become pregnant must use two methods of birth control. More information about this criterion can be found in the protocol.

• Males participating in the study must not attempt to impregnate a female, or participate in sperm donation programs. Males engaging in sexual activity that could lead to pregnancy must use a condom.

• Study candidates with a history of undefined syncope will require a complete cardiac conduction evaluation at screening [e.g., ECG, 24-hour monitoring (Holter), and exercise test (if age appropriate)]. This evaluation must rule-out any cardiac conduction abnormalities.

Exclusion Criteria for Step I:

• Active hepatitis

• Presence of an acute serious/invasive infection requiring therapy at the time of enrollment

• Hypersensitivity to any component of the formulation of ATV

• Chemotherapy for active malignancy

• Pregnant or breastfeeding

• Any clinically significant diseases (other than HIV infection) or clinically significant findings during the screening medical history or physical examination that, in the clinician's opinion, would compromise the outcome of this study

• Any laboratory or clinical toxicity greater than Grade 2 at entry

• Documented history of cardiac conduction abnormalities or significant cardiac dysfunction

• History of undefined syncope that cannot be ruled out as related to cardiac conduction abnormalities

• Family history of prolonged QTc-interval syndrome, Brugada syndrome, or right-ventricular (RV) dysplasia

• Corrected QTc-Interval greater than 440 msec at screening

• Prolonged PR-Interval greater than 0.200 seconds (200 ms) on ECG at screening (study candidates greater than or equal to 13 years of age)

• PR-Interval greater than 98th percentile on ECG at screening (study candidates less than 13 years of age)

• Cardiac rhythm abnormalities:

1. A type I second-degree atrioventricular (AV) block (Mobitz type I heart-block) occurring during waking hours on ECG at screening

2. A type II second-degree AV-block (Mobitz type II heart-block) at any time on ECG at screening

3. A complete AV-block at any time on ECG at screening

4. A heart rate less than the 2nd percentile for age of the normal heart rate range on ECG at screening

• Prolonged therapy with intravenous pentamidine for acute Pneumocystis Carinii Pneumonia (PCP) within three months of entry

Inclusion Criteria for Step II:

• Any South African subject enrolled into either part of Step I, who is virologically successful by Week 96 of when the last study participant enrolled into the respective part of Step I

• Female participants who are sexually active and able to become pregnant must continue using two methods of birth control. More information about this criterion can be found in the protocol.

• Males who continue participation in the study must not attempt to impregnate a woman, or participate in sperm donation programs. Males engaging in sexual activity that could lead to pregnancy must use a condom.

Exclusion Criteria for Step II:

• A South African participant who meets any of the criteria for treatment discontinuation by Week 96 of when the last participant enrolled into either part of Step I

• A South African participant who meets any of the exclusion criteria from Step I by Week 96 of when the last participant enrolled into either part of Step I