Dosing, Safety and Pharmacokinetic Profile of Rifabutin in Children Receiving Concomitant Treatment With Kaletra (RBT)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2010 by Harriet Shezi Children's Clinic.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Harriet Shezi Children's Clinic
ClinicalTrials.gov Identifier:
NCT01259219
First received: December 13, 2010
Last updated: December 13, 2010
Last verified: December 2010
  Purpose

Open label pharmacokinetic RBT dose-finding study in young (≤ 5 year old) HIV-infected children receiving a LPV/RTV-based ART regimen and who have a recent history of completing TB treatment.


Condition Intervention Phase
Children With Confirmed HIV Infection
Receiving ART Regimen Containing 2 NRTIs + LPV/RTV at Standard Dose
Successfully Completed TB Treatment in the Past 2 to 6 Weeks of Enrollment
Drug: Mycobutin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Dosing, Safety and Pharmacokinetic Profile of Rifabutin in Children Receiving Concomitant Treatment With Kaletra

Resource links provided by NLM:


Further study details as provided by Harriet Shezi Children's Clinic:

Primary Outcome Measures:
  • To assess dosing, pharmacokinetic profile, and safety of rifabutin when given concomitantly with LPV/RTV for 14 days in HIV-infected children age < 5 years. [ Time Frame: 6-12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • We hypothesize that a clinically significant drug interaction exists between rifabutin & /lopinavir/ritonavir in young children (age < 5 years) such that rifabutin dosing for concomitant administration of RBT & LPV/RTV needs to be developed [ Time Frame: 6-24 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: November 2010
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rifabutin (Mycobutin)
Rifabutin is a red-violet powder souble in chloroform and methanol, sparingly souluble in ethanol, and very slightly soluble in water. Mycobutin capsules contain the antimycobacterial agent rifabutin, which is a semisynthetic ansamycin antibiotic derived from rifamycin S. Mycobutin capsules for oral administered contain 150mg of rifabutin, USP, per capsule, along with the inactive ingredients microcrystalline cellulose magenesium stearate, red iron oxide3, silica gel, sodium lauryl sulfate, titanium dioxide, and edible white ink.
Drug: Mycobutin

Indication and Usage:

Mycobutin capsules are indicated for the prevention of disseminated Mycobacterium avium complex (MAC) disease in patients with advanced HIV Infection.

Dosage and Directions for use:

Mycobutin cab be administred as a single daily dose, independent of meals. In all cases Mycobutin is to be administred in combination regimens.

Identification:

Red-brown, self locking, hard gelatin capsule, size 0, containing a violet powder.


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   5 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

SELECTION AND ENROLLMENT OF SUBJECTS

Inclusion Criteria:

  • Children with confirmed HIV infection. Confirmation can be by two rapid tests (children age > 18 months) or virologic test (children < 18 months), and detectable viral load prior to starting ARVs.
  • Age ≤ 5 years old - rationale: changes in body composition and maturity of metabolizing enzymes and organs result in age-related differences in drug clearance, especially between children ≤ 5 years and children > 5 years of age.
  • Receiving an ART regimen containing 2 NRTIs + LPV/RTV at standard dose
  • Successfully completed TB treatment in the past 2 to 6 weeks. Successful completion of treatment will be defined as children with good clinical response (resolution of TB symptoms) to treatment.

Rationale:

  1. RBT has not yet been approved for treatment of TB in children. Participating children can therefore not be in need treatment for TB as this may lead to substandard treatment.
  2. RBT monotherapy in the presence of Mycobacterium tuberculosis can lead to the development of resistance. Excluding active TB is difficult in children, especially those that are HIV co-infected. Children who have just successfully completed a treatment for TB can be assumed to be free of Mycobacterium tuberculosis.
  3. A minimum of two weeks is needed between RIF and RBT administration to ensure wash-out of any enzyme inducing effects of RIF.

Exclusion Criteria

  • History of symptomatic clinical hepatitis during TB treatment
  • Abnormal liver function defined as ALT > 2.5 times the normal upper limit (corresponding to the US National Institute of Health Division of AIDS scale grade 2)
  • Abnormal bilirubin defined as > 1.5 UNL (≥ DAIDS grade 2)
  • Abnormal serum creatinine defined as >1.1 x ULN
  • Anemia defined as hemoglobin < 8gm/dL
  • Neutropenia defined as < 1.0 x 109/L(corresponding to grade 2)
  • Abnormal platelets defined as <125 x 1012/L
  • Pre-existing eye conditions
  • Any condition that the clinician feels would predispose the child to toxicity
  • Children required to take any drug known or predicted to interact with rifabutin (see appendix)
  • Children who do not meet inclusion criteria and/or whose parents refuse consent.
  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: NCT01259219

Contacts
Contact: Shobna Sawry, MSc (Med) Epi & Bio BScHonours 27119339629 shobnas@witsecho.org.za
Contact: Annelies Van Rie, MD & PhD +1919 9661420 vanrie@email.unc.edu

Locations
South Africa
Harriet Shezi Children's Clinic, Chris Hani Baragwanath Hospital, WHI, University of the Witwatersrand Recruiting
Johannesburg, Gauteng, South Africa, 1864
Contact: Hermien Gous, PharmD    27119388189    hermieng@witsecho.org.za   
Harriet Shezi Children's Clinic, Chris Hani Baragwanath Hospital, WHI, University of the Witwatersrand Recruiting
Johannesburg, Gauteng, South Africa, 1864
Principal Investigator: Henry (Harry) AJ Moultrie, MD         
Harriet Shezi Children's Clinic Recruiting
Johannesburg, Gauteng, South Africa
Contact: Sonwabo Lindani, RN    27 11 933 9392    sonwabol@witsecho.org.za   
Contact: Merleesa Govender    27 11 933 9630    merleesag@witsecho.org.za   
Sponsors and Collaborators
Harriet Shezi Children's Clinic
Investigators
Principal Investigator: Henry (Harry) JA Moultrie, MD, Master's in epi Harriet Shezi Children's Clinic, Chris Hani Baragwanth Hospital, WHI, University of the Witwatersrand
  More Information

No publications provided

Responsible Party: Dr Harry Moultrie, Harriet Shezi Children's Clinic, Chris Hani Baragwanath Hospital, WHI, University of the Witwatersrand
ClinicalTrials.gov Identifier: NCT01259219     History of Changes
Other Study ID Numbers: Rifabutin (RBT)
Study First Received: December 13, 2010
Last Updated: December 13, 2010
Health Authority: South Africa: Human Research Ethics Committee
South Africa: Medicines Control Council

Keywords provided by Harriet Shezi Children's Clinic:
HIV
Completion of TB treamtment

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Rifabutin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antitubercular
Antitubercular Agents

ClinicalTrials.gov processed this record on October 19, 2014