IMPAACT P1092: Steady State PK in Malnourished HIV Infected Children

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 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: August 5, 2015
Last verified: August 2015
  Purpose

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.


Condition Intervention Phase
HIV Positive
Malnourished
Drug: ZDV+3TC+LPV/r
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: IMPAACT 1092: Phase IV Evaluation Of The Steady State Pharmacokinetics Of Zidovudine, Lamivudine, and Lopinavir/Ritonavir in Severely Malnourished HIV-1-Infected Children

Resource links provided by NLM:


Further study details as provided by International Maternal Pediatric Adolescent AIDS Clinical Trials Group:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 50
Study Start Date: August 2015
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
Drug: ZDV+3TC+LPV/r

  Eligibility

Ages Eligible for Study:   6 Months to 36 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01818258

Contacts
Contact: Anne Coletti, MS 919-544-7040 ext 11238 acoletti@fhi360.org

Locations
Tanzania
Kilimanjaro Christian Medical Centre (5118) Not yet recruiting
Moshi, Tanzania
Contact: Blandina Mmbaga, MD, MMed, PhD    +25 576 843 5116    blaymt@gmail.com   
Contact: James Ngocho, MD    +25 578 464 0164    jamesngocho08@gmail.com   
Principal Investigator: Blandina Mmbaga, MD, MMed, PhD         
Uganda
Makerere University-Johns Hopkins University (MUJHU) Research Collaboration (30293) Not yet recruiting
Kampala, Uganda
Contact: Maxensia Owor, MBChB, MMED, MPH    +256 414 541044    maxowor@mujhu.org   
Contact: Phionah Kibalama, MBChB    +256 041 4541044    pkibalama@mujhu.org   
Principal Investigator: Maxensia Owor, MBChB, MMED, MPH         
Zimbabwe
Harare Family Care (31890) Not yet recruiting
Harare, Zimbabwe
Contact: Mutsa Bwakura-Dangarembizi, MBChB, MMed    +263 772 601735    dangas@zol.co.zw   
Contact: Hilda Mujuru, MBChB, DCH, MSc    +263 470 0877    hmujuru@mweb.co.zw   
Principal Investigator: Mutsa Bwakura-Dangarembizi, MBChB, MMed         
Sponsors and Collaborators
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Investigators
Study Chair: Maxensia O Owor, MBChB, MMED, MPH International Maternal Pediatric Adolescent AIDS Clinical Trials Group
  More Information

No publications provided

Responsible Party: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01818258     History of Changes
Other Study ID Numbers: IMPAACT P1092, U01AI068632
Study First Received: January 14, 2013
Last Updated: August 5, 2015
Health Authority: Uganda: National Council for Science and Technology

Keywords provided by International Maternal Pediatric Adolescent AIDS Clinical Trials Group:
HIV
Children
HAART
Malnourished

Additional relevant MeSH terms:
HIV Seropositivity
HIV Infections
Malnutrition
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Nutrition Disorders
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Virus Diseases
Lopinavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on August 31, 2015