Steady State PK in Malnourished HIV Infected Children (P1092)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2015 by International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Sponsor:
Collaborators:
Information provided by (Responsible Party):
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01818258
First received: January 14, 2013
Last updated: March 23, 2015
Last verified: March 2015

January 14, 2013
March 23, 2015
July 2015
September 2016   (final data collection date for primary outcome measure)
  • Safety/tolerability of ZDV, 3TC and LPV/r in severely and normal/mildly malnourished children [ Time Frame: 24 weeks following study entry ] [ Designated as safety issue: Yes ]
    numbers (percent) of subjects with at least Grade 3 adverse events related to study drugs and at least Grade 3 adverse events regardless of the relationship to study drugs.
  • PK exposure comparison between severely malnourished and normal/mildly malnourished children [ Time Frame: 1, 12, and 24 weeks following study entry ] [ Designated as safety issue: No ]
    Steady-state area under the curve (AUC) for ZDV, 3TC, and LPV/r
  • PK exposure comparison between severely malnourished and normal/mildly malnourished children [ Time Frame: 1, 12, and 24 weeks following study entry ] [ Designated as safety issue: No ]
    Plasma clearance (CL/F) for ZDV, 3TC, and LPV/r
  • Safety/ tolerability of ZDV, 3TC and Lopinavir/ritonavir (LPV/r) in severely and normal/mild malnourished children [ Time Frame: 1, 12 and 24 weeks after initiation of HAART ] [ Designated as safety issue: No ]
    numbers (percent) of subjects with at least Grade 3 adverse events related to study drugs and at least Grade 3 adverse events regardless of the relationship to study drugs.
  • PK exposure comparison between severely malnourished children with children with normal/mild malnutrition [ Time Frame: 24 weeks after initiation of HAART ] [ Designated as safety issue: Yes ]
    Steady-state Area under the curve (AUC) and plasma clearance (CL/F) for ZDV, 3TC, and LPV/r
Complete list of historical versions of study NCT01818258 on ClinicalTrials.gov Archive Site
  • Minimum concentration comparison between severely malnourished children with children with normal/mild malnutrition [ Time Frame: 1, 4, 8, 12, 16, 24, 36 and 48 weeks following study entry ] [ Designated as safety issue: No ]
    To compare the minimum trough concentration of LPV/r between severely malnourished children and children with normal nutrition - mild malnutrition at 1, 4, 8, 12, 16, 24, 36 and 48 weeks following initiation of HAART
  • LPV protein binding comparison between severely malnourished children with children with normal/mild malnutrition [ Time Frame: 1, 12 and 24 weeks following study entry ] [ Designated as safety issue: No ]
    To investigate the impact of malnutrition on LPV protein binding by comparing the free fraction of LPV in severely malnourished children and children with normal nutrition - mild malnutrition at 1, 12 and 24 weeks.
  • Minimum concentration comparison between severely malnourished children with children with normal/mild malnutrition [ Time Frame: 1, 4, 8, 12, 16, 24, 36 and 48 weeks after initiation of HAART ] [ Designated as safety issue: No ]
    To compare the minimum trough concentration of LPV/r between severely malnourished children and children with normal nutrition - mild malnutrition at 1, 4, 8, 12, 16, 24, 36 and 48 weeks following initiation of HAART
  • LPV protein binding comparison between severely malnourished children with children with normal/mild malnutrition [ Time Frame: 1, 12 and 24 weeks after initiation of HAART ] [ Designated as safety issue: No ]
    To investigate the impact of malnutrition on LPV protein binding by comparing the free fraction of LPV in severely malnourished children and children with normal nutrition - mild malnutrition at 1, 12 and 24 weeks.
Not Provided
Not Provided
 
Steady State PK in Malnourished HIV Infected Children
Phase IV Evaluation Of The Steady State Pharmacokinetics Of Zidovudine, Lamivudine, and Lopinavir/Ritonavir in Severely Malnourished HIV-1-Infected Children

HIV-infected children from sub-Saharan Africa often present with severe malnutrition. In severe malnutrition, metabolic and/or gut structural derangement may lead to inadequate antiretroviral (ARV) absorption and/or erratic drug levels. The greater surface area to weight ratio in severely malnourished children could also place them at higher risk of under dosing compared to children with mild to moderate malnutrition. However, limited data are available on the pharmacokinetics of ARVs in severely malnourished children. This study will address this critical gap in knowledge by evaluating the PK of zidovudine (ZDV), lamivudine (3TC), and lopinavir/ritonavir (LPV/r) in severely malnourished children, compared to children with normal nutrition to mild malnutrition.

Not Provided
Interventional
Phase 4
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Positive
  • Malnourished
Drug: ZDV+3TC+LPV/r
  • Active Comparator: Severe Malnutrition
    ZDV+3TC+LPV/r Zidovudine (ZDV, Retrovir®) 10 mg/ml oral syrup administered twice daily at WHO weight band dose for 48 weeks; Lamivudine (Epivir®, 3TC) 10 mg/ml for oral solution administered twice daily at WHO weight band dose for 48 weeks; Lopinavir/ritonavir (Kaletra®, LPV/r) 80/20 mg/ml oral solution administered twice daily at the WHO weight band dose for 48 weeks
    Intervention: Drug: ZDV+3TC+LPV/r
  • Active Comparator: Normal Nutrition/Mild Malnutrition
    ZDV+3TC+LPV/r Zidovudine (ZDV, Retrovir®) 10 mg/ml oral syrup administered twice daily at WHO weight band dose for 48 weeks; Lamivudine (Epivir®, 3TC) 10 mg/ml for oral solution administered twice daily at WHO weight band dose for 48 weeks; Lopinavir/ritonavir (Kaletra®, LPV/r) 80/20 mg/ml oral solution administered twice daily at the WHO weight band dose for 48 weeks
    Intervention: Drug: ZDV+3TC+LPV/r
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
50
March 2017
September 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Age ≥6 to <36 months at entry
  2. Documentation of HIV-1 infection defined as positive results from two samples collected at different time points, using protocol-specified tests
  3. Meets WHO classification for severe malnutrition, normal nutrition status, or mild malnutrition
  4. Eligible for HAART
  5. Parent or legal guardian able and willing to provide signed informed consent, remain within the study area during the study period and agree to have subject followed at the clinical site
  6. Qualifying hematology and chemistry laboratory values obtained from specimens collected within the study-specific screening period
  7. For severely malnourished children: An inpatient in a nutrition rehabilitation unit. Clinical improvement after 10-18 days on nutrition rehabilitation defined as: Appetite returned and eating better - child shows interest in food even if does not complete amount given:

    • No further weight loss
    • Normalized sodium and potassium defined as severity grade 1 or lower
    • No evidence of cardiac failure
    • Loss of apathy and starting to play
    • No hypothermia or pyrexia - temperature stable at >35.0 to <38.0° C (non-axillary) or >34.4 to <37.4° C (axillary)

For children with normal - mild malnutrition, clinical stability will be indicated by:

  • Good appetite
  • Normalized sodium and potassium defined as severity grade 1 or lower
  • No hypothermia or pyrexia - temperature stable at >35.0 to <38.0° C (non-axillary) or >34.4 to <37.4° C (axillary)

Exclusion Criteria:

  1. Edematous malnutrition at the time of study entry
  2. ≥ Grade 3 respiratory distress or presence of cardio respiratory compromise within 3 days prior to entry
  3. Chemotherapy for malignancy
  4. Acute infection for which the child has received appropriate antimicrobial treatment for <5 days
  5. Tuberculosis disease
  6. Clinic hepatitis as evidenced by jaundice and hepatomegaly
  7. Taking any disallowed medications
  8. Any condition, situation, or clinical finding that in the opinion of the investigator would place the child at an unacceptable level of risk for injury, or render the child/caregiver(s) unable to meet the requirements of the study, interfere with study participation, or in the interpretation of study results.
Both
6 Months to 36 Months
No
Contact: Anne Coletti, MS 919-544-7040 ext 11238 acoletti@fhi360.org
Tanzania,   Uganda,   Zimbabwe
 
NCT01818258
IMPAACT P1092, U01AI068632
Yes
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
  • National Institute of Allergy and Infectious Diseases (NIAID)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • National Institute of Mental Health (NIMH)
Study Chair: Maxensia O Owor, MBChB, MMED, MPH International Maternal Pediatric Adolescent AIDS Clinical Trials Group
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP