PRINCE: Study of Atazanavir (ATV)/Ritonavir (RTV)

NCT ID: NCT01099579

Last Updated: 2018-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-13
• Study Completion Date: 2017-09-11

Brief Summary

The purpose of this study is to determine whether atazanavir powder combined with ritonavir is safe and well tolerated and produces appropriate drug exposure in children ≥3 months to <6 years of age.

Conditions

HIV Infections

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Atazanavir powder, 150 mg/Ritonavir oral solution, 80 mg

Patients weighing 5 to \<10 kg received atazanavir (ATV), 150-mg powder dosed in 50-mg packets, and ritonavir (RTV) oral solution, 80 mg. Stage 1: Initial dose was determined by patient's weight on the day of first on-treatment study visit (Day 1). ATV dispersible powder was mixed with a small amount of food or beverage. All of the mixture must have been consumed to obtain the full dose. The RTV oral solution was taken immediately before or after the ATV powder preparation. Stage 2: Patients who reached the age of 6 years or a weight of ≥25kg transitioned from the powder to the capsule formulation of ATV. Patients who weighed 15 to \<20 kg received ATV, 150 mg with RTV, 100 mg; those who weighed 20 to \<40 kg received ATV, 200 mg, and RTV, 100 mg; and those who weighed at least 40 kg received ATV, 300 mg with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake.

Group Type: EXPERIMENTAL

Atazanavir powder

Intervention Type: DRUG

Powder, oral, dosed by weight. Participants who weighed 5 to \<10 kg received atazanavir (ATV), 150 mg, and ritonavir (RTV), 80 mg; those who weighed 10 to \<15 kg received ATV, 200 mg, and RTV, 80 mg; and those who weighed 15 to \<25 kg received ATV, 250 mg, and RTV, 80 mg, once per day for 48 weeks or until pediatric indication is locally approved and participant meets requirements to receive appropriate formulation.

Ritonavir oral solution

Intervention Type: DRUG

Oral solution, 80 mg/mL, once per day for 48 weeks or until pediatric indication is locally approved and participant meets requirements to receive appropriate formulation.

Atazanavir capsules

Intervention Type: DRUG

Capsules, oral, dosed by weight in Stage 2. Patients who reached the age of 6 years or a weight of ≥25 kg transitioned from the powder to the capsule formulation of atazanavir (ATV). Patients who weighed 15 to \<20 kg received ATV, 150 mg with RTV, 100 mg; those who weighed 20 to \<40 kg received ATV, 200 mg, and RTV, 100 mg; and those who weighed at least 40 kg received ATV, 300 mg with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake.

Ritonavir capsules

Intervention Type: DRUG

Oral, capsules, 100 mg, administered in Stage 2 with atazanavir capsules, dosed by weight.

Atazanavir powder, 200 mg/Ritonavir oral solution, 80 mg

Patients weighing 10 to \<15 kg received ATV powder, 200 mg, dosed in 50-mg sachet packets and RTV oral solution, 80 mg. Stage 1: Initial dose was determined by the patient's weight on the day of the first on-treatment study visit (Day 1). ATV dispersible powder was mixed with a small amount of food or beverage (water, milk, chocolate milk, liquid infant formula, applesauce, or yogurt). All of the mixture must have been consumed to obtain the full dose. The RTV oral solution was taken immediately before or after the ATV powder preparation. Stage 2: Patients who reached the age of 6 years or a weight of ≥25kg transitioned from the powder to the capsule formulation of ATV. Patients who weighed 15 to \<20 kg received ATV, 150 mg with RTV, 100 mg; those who weighed 20 to \<40 kg received ATV, 200 mg, and RTV, 100 mg; and those who weighed at least 40 kg received ATV, 300 mg with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake.

Group Type: EXPERIMENTAL

Atazanavir powder

Intervention Type: DRUG

Powder, oral, dosed by weight. Participants who weighed 5 to \<10 kg received atazanavir (ATV), 150 mg, and ritonavir (RTV), 80 mg; those who weighed 10 to \<15 kg received ATV, 200 mg, and RTV, 80 mg; and those who weighed 15 to \<25 kg received ATV, 250 mg, and RTV, 80 mg, once per day for 48 weeks or until pediatric indication is locally approved and participant meets requirements to receive appropriate formulation.

Ritonavir oral solution

Intervention Type: DRUG

Oral solution, 80 mg/mL, once per day for 48 weeks or until pediatric indication is locally approved and participant meets requirements to receive appropriate formulation.

Atazanavir capsules

Intervention Type: DRUG

Capsules, oral, dosed by weight in Stage 2. Patients who reached the age of 6 years or a weight of ≥25 kg transitioned from the powder to the capsule formulation of atazanavir (ATV). Patients who weighed 15 to \<20 kg received ATV, 150 mg with RTV, 100 mg; those who weighed 20 to \<40 kg received ATV, 200 mg, and RTV, 100 mg; and those who weighed at least 40 kg received ATV, 300 mg with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake.

Ritonavir capsules

Intervention Type: DRUG

Oral, capsules, 100 mg, administered in Stage 2 with atazanavir capsules, dosed by weight.

Atazanavir powder, 250 mg/Ritonavir oral solution, 80 mg

Patients weighing 15 to \<25 kg received 250 mg of ATV powder dosed in 50-mg sachet packets, with 80 mg of RTV solution. Stage 1: Initial dose was determined by the patient's weight on the day of the first on-treatment study visit (Day 1). ATV dispersible powder was mixed with a small amount of food or beverage (water, milk, chocolate milk, liquid infant formula, applesauce, or yogurt). All of the mixture must have been consumed to obtain the full dose. The RTV oral solution was taken immediately before or after the ATV powder preparation. Stage 2: Patients who reached the age of 6 years or a weight of ≥25kg transitioned from powder to the capsule formulation of ATV. Patients who weighed 15 to \<20 kg received ATV, 150 mg with RTV, 100 mg; those who weighed 20 to \<40 kg received ATV, 200 mg, and RTV, 100 mg; and those who weighed at least 40 kg received ATV, 300 mg with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake.

Group Type: EXPERIMENTAL

Atazanavir powder

Intervention Type: DRUG

Powder, oral, dosed by weight. Participants who weighed 5 to \<10 kg received atazanavir (ATV), 150 mg, and ritonavir (RTV), 80 mg; those who weighed 10 to \<15 kg received ATV, 200 mg, and RTV, 80 mg; and those who weighed 15 to \<25 kg received ATV, 250 mg, and RTV, 80 mg, once per day for 48 weeks or until pediatric indication is locally approved and participant meets requirements to receive appropriate formulation.

Ritonavir oral solution

Intervention Type: DRUG

Oral solution, 80 mg/mL, once per day for 48 weeks or until pediatric indication is locally approved and participant meets requirements to receive appropriate formulation.

Atazanavir capsules

Intervention Type: DRUG

Capsules, oral, dosed by weight in Stage 2. Patients who reached the age of 6 years or a weight of ≥25 kg transitioned from the powder to the capsule formulation of atazanavir (ATV). Patients who weighed 15 to \<20 kg received ATV, 150 mg with RTV, 100 mg; those who weighed 20 to \<40 kg received ATV, 200 mg, and RTV, 100 mg; and those who weighed at least 40 kg received ATV, 300 mg with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake.

Ritonavir capsules

Intervention Type: DRUG

Oral, capsules, 100 mg, administered in Stage 2 with atazanavir capsules, dosed by weight.

Interventions

Atazanavir powder

Powder, oral, dosed by weight. Participants who weighed 5 to \<10 kg received atazanavir (ATV), 150 mg, and ritonavir (RTV), 80 mg; those who weighed 10 to \<15 kg received ATV, 200 mg, and RTV, 80 mg; and those who weighed 15 to \<25 kg received ATV, 250 mg, and RTV, 80 mg, once per day for 48 weeks or until pediatric indication is locally approved and participant meets requirements to receive appropriate formulation.

Intervention Type: DRUG

Ritonavir oral solution

Oral solution, 80 mg/mL, once per day for 48 weeks or until pediatric indication is locally approved and participant meets requirements to receive appropriate formulation.

Intervention Type: DRUG

Atazanavir capsules

Capsules, oral, dosed by weight in Stage 2. Patients who reached the age of 6 years or a weight of ≥25 kg transitioned from the powder to the capsule formulation of atazanavir (ATV). Patients who weighed 15 to \<20 kg received ATV, 150 mg with RTV, 100 mg; those who weighed 20 to \<40 kg received ATV, 200 mg, and RTV, 100 mg; and those who weighed at least 40 kg received ATV, 300 mg with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake.

Intervention Type: DRUG

Ritonavir capsules

Oral, capsules, 100 mg, administered in Stage 2 with atazanavir capsules, dosed by weight.

Intervention Type: DRUG

Other Intervention Names

Reyataz; BMS-232632; Norvir

Eligibility Criteria

Inclusion Criteria

• Confirmed human immunodeficiency virus (HIV)-1 infection diagnosed by a positive virologic test result on 2 separate occasions by:

• HIV DNA polymerase chain reaction
• HIV RNA with values ≥1,000 copies/mL
• Positive HIV enzyme-linked immunosorbent assay at ≥18 months of age, with confirmatory Western blot or indirect immunoflourescence antibody
• Infants and children of either sex, aged ≥3 months to <5 years and 6 months at time of first treatment, and weight >5 to <25 kg with any screening baseline plasma viral load
• Screening plasma viral load ≥1,000 copies/mL by Roche Amplicor® HIV RNA Assay
• Documented genotypic and phenotypic sensitivity at screening to ATV (fold change in susceptibility <2.2) and to at least 2 nucleoside reverse transcriptase inhibitors (NRTIs) approved in the infant's country
• Genotypic sensitivity at screening to atazanavir (ATV) and at least 2 NRTIs
• Antiretroviral (ARV) treatment-naive or ARV treatment-experienced. Treatment-experienced participants are defined by previous exposure to ARVs through either prior treatment for HIV infection or through postnatal treatment with ≥1 ARV for the prevention of mother to child transmission. For the purposes of this study, participants exposed to ARVs in utero or intrapartum may be included in the study but will be considered treatment naive. ATV-naive participants must have genotypic sensitivity at screening to ATV (fold change in susceptibility <2.2) and to both components of the local NRTI backbone. The NRTIs must have been approved for pediatric use at the local country level.

Exclusion Criteria

• Experienced participants who received ATV or ATV/ritonavir (RTV) at any time prior to study enrollment or with a history of 2 or more protease inhibitor failures
• ARV-naïve or -experienced HIV-1 infected patients with contraindication to study medications syncope
• Family history of QTc interval syndrome, Brugada syndrome, right ventricular dysplasia, or a corrected QTc interval at screening of >440 ms
• One of the following cardiac rhythm abnormalities documented on screening electrocardiogram: 1st degree atrioventricular (AV) block as defined by protocol, type I 2nd degree AV block while awake, type II 2nd degree AV block at any time, complete AV block at any time, or age-adjusted heart rate <2nd percentile) History of pancreatitis, peripheral neuropathy, malignancy that requires systemic therapy, or any medical condition which, in the opinion of the investigator, added undue risk to trial participation
• Malabsorption syndrome
• Presence of a newly diagnosed HIV-related opportunistic infection or any medical condition requiring acute therapy at the time of enrollment
• Weight <5 or ≥25 kg at date of first dose (Day 1).
• >Grade 2 aspartate transaminase or alanine transaminase abnormalities
• Hypersensitivity to any component of the study medication formulations (ATV/RTV, or a locally prescribed NRTI with a pediatric indication)
• Infants and children of either gender <3 months or ≥5 years and 6 months at the time of first treatment.

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 66 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Local Institution

São Paulo, São Paulo, Brazil

Local Institution

Santiago, Santiago Metropolitan, Chile

Local Institution

Santiago, Santiago Metropolitan, Chile

Local Institution

Guadalajara, Jalisco, Mexico

Local Institution

Guadalajara, Jalisco, Mexico

Local Institution

Df, Mexico City, Mexico

Local Institution

Mérida, Yucatán, Mexico

Local Institution

Oaxaca City, , Mexico

Local Institution

Puebla City, , Mexico

Local Institution

Lima, , Peru

Local Institution

Lima, , Peru

Local Institution

Bloemfontein, Free State, South Africa

Local Institution

Coronationville, Gauteng, South Africa

Local Institution

Soweto, Gauteng, South Africa

Local Institution

KwaKhangela, KwaZulu-Natal, South Africa

Local Institution

Cape Town, Western Cape, South Africa

Local Institution

Bangkok, , Thailand

Local Institution

Bangkok, , Thailand

Countries

Brazil; Chile; Mexico; Peru; South Africa; Thailand

Related Links

http://bms.com/studyconnect/Pages/home.aspx

BMS Clinical Trial Patient Recruiting

http://www.bms.com/clinical_trials/Pages/Investigator_inquiry_form.aspx

Investigator Inquiry Form

Other Identifiers

2009-016361-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AI424-397

Identifier Type: -

Identifier Source: org_study_id