Advertisement

TheBodyPRO.com Covers CROI 2017

News

Dolutegravir Pharmacokinetics, Safety and Efficacy in Young Children

February 15, 2017

Dolutegravir granules-in-suspension achieved satisfactory exposures in children aged between 2 and 6 years, according to data presented at CROI2017.

Dolutegravir was potent and well tolerated through four weeks in this analysis.

IMPAACT P1093 is an ongoing phase 1/2 open-label pharmacokinetic (PK) and dose finding study of dolutegravir in age-defined paediatric cohorts: 4 weeks to <18 years of age. Doses that provide dolutegravir exposure comparable to that from 50 mg once daily in adults with acceptable safety and tolerability are selected for each age group.

Advertisement
Dolutegravir is approved for children and adolescents aged 6 years and above, weighing at least 30 kg. Theodore Ruel and colleagues from P1093 presented 4 week results from an interim analysis of the 2 to <6 years cohort.

In this study children received dolutegravir granules-in-suspension at doses of ~0.8 mg/kg mg/kg once daily. Children were ART-experienced but INSTI-naive at enrolment. They had been on a failing regimen for up to 12 weeks or off ART for at least 4 weeks. PK targets, based on adult data, were geometric means of: AUC24h range of 37-67 mg*hour/L (primary) and C24h range of 0.77-2.26 mg/L (secondary).

Intensive PK performed on 10 participants was used to determine the dose. The dolutegravir granules-in-suspension was evaluated at ~0.8 mg/kg once daily -- based on data from the older P1093 cohorts.

PK was completed after oral administration of weight-based dose between days 5-10, after which the background regimen was optimised. Safety, tolerability, and viral load were assessed at 4 weeks, and the study is ongoing to 48 weeks.

At baseline the children (5 female and 5 male) were a median: age 4.3 years (IQR 3.6-4.6); weight 15.5 kg (13.8-15.9); CD4 count 1323 cells/mm3 (IQR 763-2441); CD4 percent 28.0%(IQR 22.0-31.4) and viral load 4.8 log10 copies /mL (IQR 4.7-5.3).

Mean dolutegravir dose was 0.87 mg/kg (range 0.58-1.06). The geometric mean (CV%) AUC24h was 44.7 (36%) mg*hour/L and C24h was 0.51 (68%) mg/L. C24h was below the target but above the pharmacodynamic threshold reported in adults. There was considerable variability among the participants.

Viral load was <400 copies/mL in 8/10 participants and <50 copies/mL in 6/10 after 4 weeks of treatment. There were no Grade 3 or Grade 4 adverse events and no discontinuations due 
to adverse events.


Comment

The granules-in-suspension formulation will not be commercially available but these data will form the basis for dolutegravir dosing as dispersible tablets to be studied in this and younger age cohorts, which are now enrolling.


Reference

Ruel T et al. Dolutegravir pharmacokinetics, safety and efficacy in HIV+ children 2 to <6 years old. CROI 2017. 13-17 February 2017. Seattle, Washington. Poster abstract 806.


Related Stories

Dolutegravir Exposure Increases When Fixed-Dose Combination Tablets Are Crushed
Bictegravir versus Dolutegravir: Phase 2 Results of New Integrase Inhibitor



This article was provided by HIV i-Base. It is a part of the publication The 24th Conference on Retroviruses and Opportunistic Infections. Visit HIV i-Base's website to find out more about their activities, publications and services.
 


No comments have been made.
 

Add Your Comment:
(Please note: Your name and comment will be public, and may even show up in
Internet search results. Be careful when providing personal information! Before
adding your comment, please read TheBody.com's Comment Policy.)

Your Name:


Your Location:

(ex: San Francisco, CA)

Your Comment:

Characters remaining:


Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.

Advertisement

The content on this page is free of advertiser influence and was produced by our editorial team. See our content and advertising policies.