HIVPhase 2/3NCT01656122
Abacavir and Lamivudine PK in Children
A Phase 2/3 study testing abacavir and 3TC in people with HIV, run by The HIV Netherlands Australia Thailand Research Collaboration at 1 site in Thailand.
Trial summary
The purpose of this study is to assess the pharmacokinetic parameters for ABC and 3TC in HIV-infected children younger than 18 years old with body weight ≥ 14 kgs. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- HIV
- What is being tested?
- abacavir and 3TC
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteThailand
- Study dates
- Jul 2012to Jul 2015
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Have a diagnosis of HIV infection using age-appropriate testing
- Age < 18 years
- Body weight ≥ 14 kgs
- Currently treated with stable HAART within 30 days prior to enrollment
- HIV RNA < 50 copies/ml
- Have negative HLA B5701 or are currently on ABC-containing HAART and tolerating the regimen well
- Caregivers give written informed consent and children aged 7 years and above who know their HIV status give assent
Who cannot join
- Child/Caretaker refuse to participate in this study
- Has vomiting or diarrhea > grade 3 (DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 1.0 - December 2004, clarification dated August 2009) within 30 days prior to enrollment
- Has the following laboratory toxicities > grade II according to the division of AIDS table for grading the severity of adult and pediatric adverse events within 30 days prior to enrollment:
- SGPT
- Hemoglobin
- Creatinine
Show all 11Show fewer
- Has current active HIV-related infection
- Has significant medical problem that would compromise the study results in the investigator's opinion
- Pregnancy
- Has history of poor adherence to ARV defined by less than 80% by pill count or by history within 30 days prior to enrollment
- Concomitant treatment with drugs known to influence the PK of ABC (ribavirin, ethanol and methadone)
Trial locations and contacts
1 site in 1 country.
Thailand1 site
The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)
Bangkok, 10330
About this study
Official title: Pharmacokinetics of Abacavir Once Daily vs. Twice Daily and Lamivudine Once Daily vs. Twice Daily in HIV-infected Thai Children
The purpose of this study is to assess the pharmacokinetic parameters for ABC and 3TC in HIV-infected children younger than 18 years old with body weight ≥ 14 kgs.
Read the detailed description
Abacavir (ABC) is a nucleoside reverse transcriptase inhibitor (NRTI) and continues to have good efficacy even in patients who have some resistant mutations to NRTIs. ABC is approved for use in children 3 months old and up. It is a preferred NRTI option for second line treatment in children in the World Health Organization guidelines (WHO). In the US and European guidelines, ABC is also recommended for first line treatment. Published studies support the efficacy and safety of twice and once daily ABC. In HIV-infected children < 12 years, ABC is licensed twice-daily only. However, ABC is licensed either twice-daily or once-daily for HIV-infected adults and children >12 years. In addition, ABC can be administered as the fixed dose combination once-daily with lamivudine (3TC), Kivexa, for HIV-infected adults and children >12 years.
Lamivudine (3TC) is a commonly used NRTI that is well tolerated and approved for young infants and children as a component in the first and second-line regimens in guidelines. Both once-daily and twice-daily 3TC are standard practice in many treatment guidelines although once-daily is US FDA-approved for age > 12 years only. The Thai Ministry of Health pediatric HIV treatment guideline recommend either once- or twice-daily as treatment options for children. The WHO currently recommends the twice-daily 3TC dosing only and encourages more pharmacokinetic studies of once-daily 3TC in children.
PK of ABC and 3TC in African and European children showed similar PK parameters for both twice daily and once daily dosing. There are no data on PK of ABC in Asian children and few studies on PK of 3TC in Thai children. Vanprapar et al. reported data in 42 Thai children weighing 6-30 kg participated in a cross-over PK study in which they received twice-daily dosing of generic fixed dose combination tablets of stavudine, 3TC, nevirapine or the liquid formulations of these drugs. The 3TC exposure was significantly higher with the tablet formulation but comparable to historical data in western adults and children taking branded tablets. Chokephaibulkit et al. reported higher 3TC exposure in 41 Thai HIV-infected children with 3TC tablets than 3TC solution.
There is strong evidence indicating that Asian patients, particularly Thais, have higher plasma concentrations for several ARVs compared to Westerners. Genetic differences between ethnicities may be the primary cause for altered drug metabolism, and as a result, different PK parameters. Higher drug concentrations in Thai adults have been shown for zidovudine, nevirapine, efavirenz, indinavir, lopinavir, atazanavir and saquinavir. Such high ARV concentrations were also shown in Thai children for nevirapine, indinavir, lopinavir and saquinavir. There are no data in Thai children for ABC. Only two studies evaluated 3TC concentration in Thai children using twice-daily dosing. It is conceivable that Thai children may have different PK profile of ABC and 3TC particularly once-daily dosing and than those reported in African and European children. In addition, using ABC and 3TC will provide an opportunity for Thai children to benefit from its once-daily dosing and good long-term safety particularly the favorable lipodystrophy and lipid profile.
- Conditions
- HIV
- Being tested
- abacavir, 3TC
- Keywords
- pharmacokinetic paramters, abacavir, lamuvidine, HIV-infected children
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
abacavirDrug
Dosing of ABC will be according to the WHO guidelines by weight band for twice daily dosing. The once daily dosing will use the same mg/day as the twice daily dosing for that weight band
3TCDrug
Dosing of 3TC will be according to the WHO guidelines by weight band for twice daily dosing. The once-daily dosing will use the same mg/day as the twice-daily dosing for that weight band
| Study group | Role | What they receive |
|---|---|---|
| PK | Experimental | PK of abacavir and lamivudine Receives: Drug: abacavir; Drug: 3TC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ctrough and Area under the curve (AUC) of abacavir (ABC) and lamivudine (3TC) at week 2 and 4
assess the Ctrough and Area under the curve (AUC) of abacavir (ABC) and lamivudine (3TC) at week 2 twice daily dose and week 4 once daily dose
Measured: week 96
Secondary outcomes (2)
CD4
assess CD4 at weeks 48 and 96
Measured: 96 weeks
viral load
assess viral load at weeks 48 and 96
Measured: 96 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2012 (estimated)
- Study startJul 2012
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- The HIV Netherlands Australia Thailand Research Collaboration
- Sponsor type
- University, hospital or other
- Collaborators
- Radboud University Medical Center, amfAR, The Foundation for AIDS Research, PHPT/AMS Laboratory, Faculty of Associated Medical Sciences, Chiang Mai University, Chulalongkorn University, ViiV Healthcare
- Responsible party
- Sponsor
- Investigators
- Jintanat Ananworanich, MD, PhD, Principal investigator, The HIV Netherlands Australia Thailand Research Collaboration
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01656122
- Sponsor's protocol ID
- HIV-NAT 167
- Status last verified
- Feb 2016
- First submitted
- 17 Jul 2012
- Last updated
- 22 Feb 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Bunupuradah T, Punyahotra P, Cressey TR, Srimuan A, Thammajaruk N, Sophonphan J, Sriheara C, Burger DM, Puthanakit T, Ananworanich J. Plasma pharmacokinetics of once-daily abacavir- and lamivudine-containing regimens and week 96 efficacy in HIV-infected Thai children. J Virus Erad. 2015 Jul 1;1(3):185-91. doi: 10.1016/S2055-6640(20)30503-3.
PubMed 27482411
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Abacavir Once Daily vs. Twice Daily and Lamivudine Once Daily vs. Twice Daily in HIV-infected Thai Children
- ClinicalTrials.gov ID
- NCT01656122
- Acronym / sponsor ID
- HIV-NAT 167
- Conditions
- HIV
- Keywords
- pharmacokinetic paramters, abacavir, lamuvidine, HIV-infected children
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- The HIV Netherlands Australia Thailand Research CollaborationUniversity, hospital or other
- Collaborators
- Radboud University Medical Center, amfAR, The Foundation for AIDS Research, PHPT/AMS Laboratory, Faculty of Associated Medical Sciences, Chiang Mai University, Chulalongkorn University, ViiV Healthcare
- Study start
- Jul 2012
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 2 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the pharmacokinetic parameters for ABC and 3TC in HIV-infected children younger than 18 years old with body weight ≥ 14 kgs.
Detailed description
Abacavir (ABC) is a nucleoside reverse transcriptase inhibitor (NRTI) and continues to have good efficacy even in patients who have some resistant mutations to NRTIs. ABC is approved for use in children 3 months old and up. It is a preferred NRTI option for second line treatment in children in the World Health Organization guidelines (WHO). In the US and European guidelines, ABC is also recommended for first line treatment. Published studies support the efficacy and safety of twice and once daily ABC. In HIV-infected children < 12 years, ABC is licensed twice-daily only. However, ABC is licensed either twice-daily or once-daily for HIV-infected adults and children >12 years. In addition, ABC can be administered as the fixed dose combination once-daily with lamivudine (3TC), Kivexa, for HIV-infected adults and children >12 years.
Lamivudine (3TC) is a commonly used NRTI that is well tolerated and approved for young infants and children as a component in the first and second-line regimens in guidelines. Both once-daily and twice-daily 3TC are standard practice in many treatment guidelines although once-daily is US FDA-approved for age > 12 years only. The Thai Ministry of Health pediatric HIV treatment guideline recommend either once- or twice-daily as treatment options for children. The WHO currently recommends the twice-daily 3TC dosing only and encourages more pharmacokinetic studies of once-daily 3TC in children.
PK of ABC and 3TC in African and European children showed similar PK parameters for both twice daily and once daily dosing. There are no data on PK of ABC in Asian children and few studies on PK of 3TC in Thai children. Vanprapar et al. reported data in 42 Thai children weighing 6-30 kg participated in a cross-over PK study in which they received twice-daily dosing of generic fixed dose combination tablets of stavudine, 3TC, nevirapine or the liquid formulations of these drugs. The 3TC exposure was significantly higher with the tablet formulation but comparable to historical data in western adults and children taking branded tablets. Chokephaibulkit et al. reported higher 3TC exposure in 41 Thai HIV-infected children with 3TC tablets than 3TC solution.
There is strong evidence indicating that Asian patients, particularly Thais, have higher plasma concentrations for several ARVs compared to Westerners. Genetic differences between ethnicities may be the primary cause for altered drug metabolism, and as a result, different PK parameters. Higher drug concentrations in Thai adults have been shown for zidovudine, nevirapine, efavirenz, indinavir, lopinavir, atazanavir and saquinavir. Such high ARV concentrations were also shown in Thai children for nevirapine, indinavir, lopinavir and saquinavir. There are no data in Thai children for ABC. Only two studies evaluated 3TC concentration in Thai children using twice-daily dosing. It is conceivable that Thai children may have different PK profile of ABC and 3TC particularly once-daily dosing and than those reported in African and European children. In addition, using ABC and 3TC will provide an opportunity for Thai children to benefit from its once-daily dosing and good long-term safety particularly the favorable lipodystrophy and lipid profile.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PK | Experimental | Drug: abacavir, Drug: 3TCPK of abacavir and lamivudine |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Have a diagnosis of HIV infection using age-appropriate testing
- Age < 18 years
- Body weight ≥ 14 kgs
- Currently treated with stable HAART within 30 days prior to enrollment
- HIV RNA < 50 copies/ml
Key exclusion criteria (11 listed)
- Child/Caretaker refuse to participate in this study
- Has vomiting or diarrhea > grade 3 (DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 1.0 - December 2004, clarification dated August 2009) within 30 days prior to enrollment
- Has the following laboratory toxicities > grade II according to the division of AIDS table for grading the severity of adult and pediatric adverse events within 30 days prior to enrollment:
- Has current active HIV-related infection
- Has significant medical problem that would compromise the study results in the investigator's opinion
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| abacavirDosing of ABC will be according to the WHO guidelines by weight band for twice daily dosing. The once daily dosing will use the same mg/day as the twice daily dosing for that weight band | Drug | PK |
| 3TCDosing of 3TC will be according to the WHO guidelines by weight band for twice daily dosing. The once-daily dosing will use the same mg/day as the twice-daily dosing for that weight band | Drug | PK |
Primary outcome
Ctrough and Area under the curve (AUC) of abacavir (ABC) and lamivudine (3TC) at week 2 and 4
Time frame: week 96
assess the Ctrough and Area under the curve (AUC) of abacavir (ABC) and lamivudine (3TC) at week 2 twice daily dose and week 4 once daily dose
2 secondary outcomes
CD4
Time frame: 96 weeks
viral load
Time frame: 96 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2016.
- Results publication: PubMed 27482411Bunupuradah T, Punyahotra P, Cressey TR, Srimuan A, Thammajaruk N, Sophonphan J, Sriheara C, Burger DM, Puthanakit T, Ananworanich J. Plasma pharmacokinetics of once-daily abacavir- and lamivudine-containing regimens and week 96 efficacy in HIV-infected Thai children. J Virus Erad. 2015 Jul 1;1(3):185-91. doi: 10.1016/S2055-6640(20)30503-3.
- HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jintanat Ananworanich, MD, PhD principal investigator
The HIV Netherlands Australia Thailand Research Collaboration
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing abacavir and 3TC in people with HIV, run by The HIV Netherlands Australia Thailand Research Collaboration at 1 site in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ctrough and Area under the curve (AUC) of abacavir (ABC) and lamivudine (3TC) at week 2 and 4 (time frame: week 96). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01656122, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2016.