Condition category
Infections and Infestations
Date applied
16/06/2009
Date assigned
10/07/2009
Last edited
24/06/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Elizabeth Grace Hermione Lyall

ORCID ID

Contact details

Dept of Pediatrics
St Mary's Hospital
South Wharf Road
London
W2 1NY
United Kingdom
-
Hermione.lyall@imperial.nhs.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

PENTA18 version 1.0

Study information

Scientific title

PENTA18: A study of the pharmacokinetics, safety and efficacy of twice-daily versus once-daily lopinavir/ritonavir tablets dosed by weight as part of combination antiretroviral therapy in human immunodeficiency virus-1 (HIV-1) infected children

Acronym

PENTA18

Study hypothesis

The trial will evaluate the pharmacokinetics, safety, efficacy and acceptability of twice- and once-daily dosing of lopinavir/ritonavir tablets (Kaletra®) dosed by weight in human immunodeficiency virus-1 (HIV-1) infected children who are currently taking lopinavir/ritonavir as part of their combination antiretroviral therapy and who are currently achieving virological suppression (less than 50 copies/ml). Specifically:
1. To confirm weight-based dosing recommendations by evaluating the pharmacokinetics of twice-daily lopinavir/ritonavir half strength formulation tablets dosed on body weight and comparing to historical adult and paediatric data of pharmacokinetics of lopinavir/ritonavir soft gel capsules and oral solution respectively
2. To compare the pharmacokinetics of twice-daily lopinavir/ritonavir tablets with once-daily dosing in the same children
3. To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression at 48 weeks. Adherence and acceptability will also be compared.

Ethics approval

Trent Research Ethics Committee, 12/01/2010, ref: 09/H0405/49

Study design

Open-label multicentre randomised phase II/III trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Infectious disease - Paediatric HIV

Intervention

Children will already be taking lopinavir/ritonavir. Dosage should be adjusted to the FDA approved daily doses (based on weight bands) as part of their combined ART. Children will be randomised to take lopinavir/ritonavir once daily or twice daily (same total daily dose). Children will continue into this dosing unless they reach protocol defined criteria to switch therapy. All children will be followed until the last participant has completed 48 week follow-up.

Intervention type

Drug

Phase

Phase II/III

Drug names

Lopinavir/ritonavir (Kaletra®)

Primary outcome measures

1. HIV-1 RNA greater than or equal to 400 copies/ml (confirmed) at any of week 4, 8, 12, 24, 36 or 48
2. Area under curve (AUC), Cmin and Cmax values of lopinavir after twice-daily dosing compared to historical adult and paediatric data
3. AUC, Cmin and Cmax values of lopinavir after once-daily and twice-daily dosing (in the same children)

Secondary outcome measures

1. HIV-1 RNA less than 400/less than 50 copies/ml at 24 and 48 weeks
2. HIV-1 RNA greater than or equal to 50 and less than 400 copies/ml at any of week 4, 8, 12, 24, 36 or 48
3. Number of HIV mutations present at week 4, 8, 12, 24, 36 or 48 conferring resistance to drugs taken at randomisation or during the trial
4. Change in CD4 (absolute and percentage) from baseline to 24 and 48 weeks
5. Change in ART (defined as any change from the ART regimen at randomisation)
6. ART-related grade 3 or 4 clinical and laboratory adverse events
7. New Centers for Disease Control and Prevention (CDC) stage C diagnosis or death
8. Cchild and family acceptability of and adherence to twice-daily lopinavir/ritonavir 100/25 mg tablets dosed on body weight, over 48 weeks as assessed by patient/carer completed questionnaires
9. Child and family acceptability of and adherence to once-daily compared to twice-daily dosing of lopinavir/ritonavir tablets, over 48 weeks as assessed by patient/carer completed questionnaires

Overall trial start date

30/09/2009

Overall trial end date

01/10/2012

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged less than 18 years (up to 18th birthday) with confirmed HIV-1 infection, either sex
2. Weight greater than or equal to 15 kg
3. Able to swallow tablets
4. Stable (i.e. CD4 not declining) on a combination antiretroviral regimen that has included lopinavir/ritonavir for at least 24 weeks, and expected to stay on the same regimen for the next 48 weeks
5. Taking lopinavir/ritonavir dosed twice-daily and be willing at the screening visit to change to tablet formulation (if not currently taking tablets) and to change the lopinavir/ritonavir dose to follow the recommended FDA dosing plan based on body weight bands as necessary; if participating in the PK study, be willing at the screening visit to change to lopinavir/ritonavir half strength formulation tablets (100/25 mg) only, dosed twice-daily and change the lopinavir/ritonavir dose to follow the recommended FDA dosing plan based on body weight bands as necessary
6. Viral suppression (HIV-1 ribonucleic acid [RNA] less than 50 copies/ml) for at least the prior 24 weeks (minimum of two measurements)
7. Children and caregivers willing to participate in the PK study if they are among a minimum of the first 16 children enrolled in each body weight band in the trial, including a second PK assessment if randomised to switch to once-daily lopinavir/ritonavir
8. Parents/carers and children, where applicable, give informed written consent

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

160

Participant exclusion criteria

1. Children on an antiretroviral regimen that includes a non-nucleoside reverse transcriptase inhibitor (NNRTI), fosamprenavir or nelfinavir
2. Children who have previously failed virologically on a protease inhibitor (PI)-containing regimen (where virological failure is defined as two successive HIV-1 ribonucleic acid [RNA] results greater than 1000 copies/ml [confirmed] more than 24 weeks after starting highly active anti-retroviral therapy [HAART], i.e changes for toxicity are not counted as failure)
3. Intercurrent illness
4. Abnormal renal or liver function (grade 3 or above)
5. Receiving concomitant therapy except prophylactic antibiotics
6. Pregnancy or risk of pregnancy in females of child-bearing potential

Recruitment start date

30/09/2009

Recruitment end date

01/10/2012

Locations

Countries of recruitment

Austria, Belgium, Brazil, Denmark, Germany, Ireland, Italy, Netherlands, Poland, Spain, Sweden, Thailand, United Kingdom

Trial participating centre

St Mary's Hospital
London
W2 1NY
United Kingdom

Sponsor information

Organisation

The PENTA Foundation (Italy)

Sponsor details

c/o Dr Carlo Giaquinto
Clinica Pediatrica
Universita di Padova
Via Gustiniani 3
Padova
31528
Italy
-
carlog@pediatria.unipd.it

Sponsor type

Charity

Website

http://www.ctu.mrc.ac.uk/penta

Funders

Funder type

Charity

Funder name

The PENTA Foundation (Italy)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24356253

Publication citations

Additional files

Editorial Notes