HIV Infection
Conditions
Keywords
HIV, Abacavir, Lamivudine, Pharmacokinetics
Brief summary
To compare the plasma pharmacokinetic (PK) parameters of q24h versus q12h dosing of abacavir in HIV-1-infected infants and children aged 3 months to 36 months The secondary objectives of PENTA15 were: To compare the plasma PK parameters of q24h versus q12h dosing of lamivudine in HIV-1-infected infants and children aged 3 months to 36 months who were receiving lamivudine in combination with abacavir To compare age-related differences in the PK parameters of q24h versus q12h dosing of abacavir and lamivudine infants and children in 3 age groups (≥3 to \<12 months, ≥12 to \<24 months and ≥24 to \<36 months) To describe child and family acceptability of and adherence to q24h compared to q12h dosage regimens of abacavir and lamivudine
Interventions
OTHERIntervention 1: PK assessment while on Twice Daily Abacavir
Week 0
OTHERIntervention 2: PK assessment while on Once Daily Abacavir
Week 4
Sponsors
PENTA Foundation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Months to 36 Months
Healthy volunteers
No
Inclusion criteria
* Infants and children with confirmed presence of HIV-1 infection * Infants and children aged 3 to \<36 months * Parents/guardians able and willing to give written, informed consent * Currently on combination ART including Abacavir (ABC) oral solution with or without Lamivudine (3TC) oral solution, for at least 12 weeks and expected to stay on this regimen for at least a further 12 weeks. * HIV-1 RNA viral load either; * suppressed HIV-1 RNA viral load (i.e. \<400 copies/ml) * non-suppressed, but low, HIV-1 RNA viral load (i.e. 400-20 000 copies/ml). The non-suppressed children should have had a stable or decreasing HIV-1 RNA viral load prior to study entry and should be considered to be still gaining benefit from the current regimen * Stable or rising CD4+ cell percent prior to study entry and should not be expected to fall within the next 12 weeks.
Exclusion criteria
* Intercurrent illness * Receiving concomitant therapy except prophylactic antibiotics * Abnormal renal or liver function (grade 3 or above)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under Curve (AUC) (0-24) of Abacavir on Twice Daily Dosing | Week 0 | Blood samples were taken at 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 12 hours post-ingestion of medication. |
| Cmax of Abacavir on Twice Daily Dosing | Week 0 | Blood samples were taken at 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 12 hours post-ingestion of medication. |
| AUC(0-24) of Abacavir on Once Daily Dosing | Week 4 | Blood samples were taken at 0 (pre-dose), 1, 2, 3, 4, 6, 8, 12 and 24 hours post-ingestion of medication |
| Cmax of Abacavir on Once Daily Dosing | Week 4 | Blood samples were taken at 0 (pre-dose), 1, 2, 3, 4, 6, 8, 12 and 24 hours post-ingestion of medication. |
Countries
France, Germany, Italy, Spain, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Arm This is a single arm crossover study First intervention: PK assessment while on Twice Daily Abacavir Second intervention: PK assessment while on Once Daily Abacavir | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost samples from one PK Day | 2 |
| Overall Study | PK curve incomplete | 2 |
| Overall Study | Vomiting after commencing once daily | 1 |
Baseline characteristics
| Characteristic | Single Arm |
|---|---|
| Age, Categorical <=18 years | 18 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Race/Ethnicity, Customized Black, African or other | 14 participants |
| Race/Ethnicity, Customized Mixed Black/White | 1 participants |
| Race/Ethnicity, Customized White | 3 participants |
| Region of Enrollment France | 3 participants |
| Region of Enrollment Germany | 3 participants |
| Region of Enrollment Italy | 1 participants |
| Region of Enrollment Spain | 2 participants |
| Region of Enrollment United Kingdom | 9 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 23 |
| serious Total, serious adverse events | 4 / 23 |
Outcome results
Primary
Area Under Curve (AUC) (0-24) of Abacavir on Twice Daily Dosing
Blood samples were taken at 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 12 hours post-ingestion of medication.
Time frame: Week 0
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Single Arm | Area Under Curve (AUC) (0-24) of Abacavir on Twice Daily Dosing | 10.85 h*mg/L |
Primary
AUC(0-24) of Abacavir on Once Daily Dosing
Blood samples were taken at 0 (pre-dose), 1, 2, 3, 4, 6, 8, 12 and 24 hours post-ingestion of medication
Time frame: Week 4
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Single Arm | AUC(0-24) of Abacavir on Once Daily Dosing | 11.57 h*mg/L |
Primary
Cmax of Abacavir on Once Daily Dosing
Blood samples were taken at 0 (pre-dose), 1, 2, 3, 4, 6, 8, 12 and 24 hours post-ingestion of medication.
Time frame: Week 4
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Single Arm | Cmax of Abacavir on Once Daily Dosing | 4.68 mg/L |
Primary
Cmax of Abacavir on Twice Daily Dosing
Blood samples were taken at 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 12 hours post-ingestion of medication.
Time frame: Week 0
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Single Arm | Cmax of Abacavir on Twice Daily Dosing | 2.29 mg/L |