Phase IIIB Study Evaluating the Effects of Atazanavir Powder With Ritonavir in HIV-infected Pediatric Patients

NCT01335698 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: AI424-4512010-024537-23
• Study Type: interventional
• Target: 160
• Locations: 11 countries
• Sites: 32

Brief Summary

The purpose of this study is to describe the safety, efficacy, and pharmacokinetics of a regimen of atazanavir powder boosted with ritonavir and an optimized dual nucleoside reverse transcriptase inhibitor in pediatric patients aged ≥3 months to \<11 years.

Conditions

HIV

Keywords

Pediatric

Outcome Measures

Primary Outcomes (4)

• Number of Participants Who Died and With Adverse Events (AEs) Leading to Discontinuation, Hyperbilirubinemia, Jaundice, First-degree Arterioventricular Block, Tachycardia, and Rash on ATV Powder

  AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.

  Day one to week 300 (approximately 22-Jan-2018)

• Number of Participants Who Experienced a SAE on ATV Powder

  SAE= any of the the following: is life-threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event (defined as a medical event(s) that may not be immediately life threatening or result in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the subject or may require intervention \[eg, medical, surgical\] to prevent one of the other serious outcomes listed in the definition above.) Examples of such events include, but are not limited to, intensive treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization

  Day one to week 300 (approximately 22-Jan-2018)

• Number of Participants With A Center of Disease Control and Prevention (CDC) Class C AIDS Event on ATV Powder

  The CDC disease staging system assesses the severity of HIV disease by CD4 cell counts and by the presence of specific HIV-related conditions. CD4 counts are classified as 1: ≥500 cells/µL, 2: 200-499 cells/µL, and 3: \<200 cells/µL. Children with HIV infection are also classified in each of several categories. Category N: Not symptomatic. Category A: Mildly symptomatic. Category B: Moderately symptomatic. Category C: Severely symptomatic.

  Day one to week 300 (approximately 22-Jan-2018)

• Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality on ATV Powder

  Criteria of the Division of AIDS for grading the severity of adult and pediatric adverse events as follows: Grade (Gr) 1=mild; Gr 2=moderate; Gr 3=severe; Gr 4=potentially life-threatening. Neutrophils (absolute) (adult and infants \>7 days): Gr 1=1.000-1300/mm\^3; Gr 2=750-999 mm\^3; Gr 3=500-749 mm\^3; Gr 4= \<500 mm\^3. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase: Gr 1=1.25-2.5\*upper limit of normal (ULN); Gr 2=2.6-5.0\*ULN; Gr 3=5.1-10.0\*ULN; Gr 4= \>10.0\*ULN. Bilirubin, total (adults and infants \>14 days): Gr 1=1.1-1.5\*ULN; Gr 2=1.6-2.5\*ULN; Gr 3=2.6-5.0\*ULN; Gr 4= \>5.0\*ULN. Lipase: Gr 1=1.1-1.5\*ULN; Gr 2=1.6-3.0\*ULN; Gr 3=3.1-5.0\*ULN; Gr 4= \>5.0\*ULN. Bicarbonate, serum low: Gr 1=16.0 mEq/L-\<lower limit of normal; Gr 2=11.0-15.9 mEq/L; Gr 3=8.0-10.9 mEq/L; Gr 4= \<8 mEq/L. By criteria of the World Health Organization: Amylase: Gr 1=1.0-1.39\*ULN; Gr 2=1.40-2.09\*ULN; Gr 3.=2.10-5.0\*ULN; Gr 4= \>5.0\*ULN.

  Day one to week 300 (approximately 22-Jan-2018)

Secondary Outcomes (8)

• Number of Participants With HIV RNA <50 Copies/mL and <400 Copies/mL in the Week 24 Atazanavir Powder Cohort and the Eligible Week 48 Atazanavir Powder Cohort

  Day 1 of treatment to weeks 24 and 48

• Mean Change From Baseline in HIV RNA on ATV Powder

  Baseline to Weeks 24 and 48

• Mean Change From Baseline in CD4 Percent on ATV Powder

  Baseline to Weeks 24 and 48

• CD4 Cell Count Changes From Baseline on ATV Powder

  Baseline to Weeks 24 and 48

• Number of Participants With Emergent Genotypic Substitutions on ATV Powder Through Week 48

  Baseline through Week 48

Study Arms (1)

Stage 1: Atazanavir + Ritonavir

EXPERIMENTAL

Participants received atazanavir powder orally (dosed by weight: 5 to \<10 kg=150 mg, 5 to \<10 kg=200 mg, 10 to \<15 kg=200 mg, 15 to \<25 kg=250 mg, 25 to \<35 kg=300 mg) once daily for 24 to 48 weeks or a weight ≥35 kg. Participants also received ritonavir once daily for 24 to 48 weeks or weight ≥35 kg in the form of 80-mg/mL solution, orally (dosed by weight 5 to \<25 kg=80 mg, 25 to \<35 kg=100 mg); 100-mg capsule, orally (dosed by weight 25 to \<35 kg=100 mg); or 100-mg tablet, orally (dosed by weight 25 to \<35 kg=100 mg)

Drug: Atazanavir Sulphate; Drug: Ritonavir

Interventions

Atazanavir Sulphate DRUG

Also known as: Reyataz, BMS-232632

Stage 1: Atazanavir + Ritonavir

Ritonavir DRUG

Also known as: Norvir

Stage 1: Atazanavir + Ritonavir

Eligibility Criteria

• Age: 3 Months - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Confirmed HIV-1 infection diagnosed by protocol criteria
• Screening HIV RNA level ≥1000 copies/mL
• ≥3 months to \<11 years of age at time of first treatment
• Antiretroviral-naive or -experienced
• At screening, all participants must have genotypic sensitivity to atazanavir and at least 2 nucleoside reverse transcriptase inhibitors (NRTIs), which must be approved for pediatric use at the local country.
• Antiretroviral-experienced patients must also have documented phenotypic sensitivity at screening to atazanavir (Fold Change in susceptibility \<2.2) and to at least 2 NRTIs that are approved in their country

You may not qualify if:

• Experienced participants who received atazanavir or atazanavir/ritonavir at any time prior to study enrollment or who have a history of 2 or more protease inhibitor failures
• Antiretroviral-naïve or -experienced HIV-1-infected patients with contraindication to study medications
• Cardiac rhythm abnormalities
• Need for tenofovir
• Weight \<5 or ≥35kg
• \>Grade 2 abnormality in aspartate transaminase/alanine transaminase levels
• Coinfection with either hepatitis B or C virus
• Any active Centers for Disease Control and Prevention Category C clinical condition

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (32)

Children'S National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Local Institution

Buenos Aires, Bs As, Buenos Aires, 1141, Argentina

Location

Local Institution

Bunos Aires, Buenos Aires, 1425, Argentina

Location

Local Institution

Recife, Pernambuco, 50070-500, Brazil

Location

Local Institution

Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

Location

Local Institution

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Local Institution

Ribeirão Preto, São Paulo, 14049-900, Brazil

Location

Local Institution

Santiago, Santiago Metropolitan, 8380418, Chile

Location

Local Institution

Santiago, Santiago Metropolitan, Chile

Location

Local Institution

Guadalajara, Jalisco, 44160, Mexico

Location

Local Institution

Guadalajara, Jalisco, 44280, Mexico

Location

Local Institution

Df, Mexico City, 06720, Mexico

Location

Local Institution

Mérida, Yucatán, 97000, Mexico

Location

Local Institution

Oaxaca City, 71256, Mexico

Location

Local Institution

Puebla City, 72000, Mexico

Location

Local Institution

Warsaw, 01-201, Poland

Location

Local Institution

Bucharest, 72205, Romania

Location

Local Institution

Saint Petersburg, 189635, Russia

Location

Local Institution

Saint Petersburg, 198103, Russia

Location

Local Institution

Smolensk, 214006, Russia

Location

Local Institution

Port Elizabeth, Eastern Cape, 6001, South Africa

Location

Local Institution

Port Elizabeth, Eastern Cape, 6014, South Africa

Location

Local Institution

Bloemfontein, Free State, 9301, South Africa

Location

Local Institution

Benoni, Gauteng, 1501, South Africa

Location

Local Institution

Coronationville, Gauteng, 2092, South Africa

Location

Local Institution

Pretoria, Gauteng, 0001, South Africa

Location

Local Institution

Soweto, Gauteng, 2001, South Africa

Location

Local Institution

Parrow Valley, Western Cape, 7505, South Africa

Location

Local Institution

Barcelona, 08950, Spain

Location

Local Institution

Madrid, 28041, Spain

Location

Local Institution

Birmingham, WEST Midlands, B9 5ST, United Kingdom

Location

Related Links

• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form

MeSH Terms

Interventions

Atazanavir Sulfate; Ritonavir

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2011
• First Posted: April 14, 2011
• Study Start: May 27, 2011
• Primary Completion: September 10, 2014
• Study Completion: January 22, 2018
• Last Updated: November 9, 2018
• Results First Posted: February 8, 2016

Record last verified: 2018-10

Locations

ZA (8); BR (4); ES (2); PL (1); GB (1); ME (6); CL (2); RU (3); US (2); RO (1); AR (2)