HIV InfectionsPhase 1/2NCT01302847
Safety of and Immune Response to Dolutegravir in HIV-1 Infected Infants, Children, and Adolescents
A Phase 1/2 study testing DTG film-coated tablets, DTG granules for suspension and DTG dispersible tablets in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 33 sites in 8 countries.
Trial summary
Dolutegravir (DTG) is an HIV drug in the integrase inhibitor drug class. This study evaluated the pharmacokinetics (PK), safety, tolerability of and immune response to DTG when used concurrently with optimized background therapy (OBT) in HIV-1 infected infants, children, and adolescents. Read more about this study
- Who is it for?
- Ages 4 weeks to 17 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- DTG film-coated tablets, DTG granules for suspension and DTG dispersible tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 181 participants
- Where
- 33 sitesin 8 countries
- Study dates
- 20 Apr 2011to 18 Oct 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 4 weeks to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Confirmed HIV-1 infection, defined as positive results from two samples collected at different time points (see protocol for more information)
- Participant belonged to one of the ARV exposure groups below:
- ARV-treatment experienced (not including receipt of ARVs as prophylaxis or for prevention of perinatal transmission)
- Previously took ARVs for treatment, but not taking ARVs at study screening.
- Had been off treatment for greater than or equal to 4 weeks prior to screening, OR
- At screening, taking ARVs for treatment but failing.
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- Was on an unchanged, failing therapeutic regimen within the 4 to 12 weeks prior to screening (less than or equal to 1 log drop in HIV-1 RNA within the 4 to 12 weeks prior to screening). OR
- For participants less than 2 years of age, initiated ARVs for treatment less than 4 weeks prior to screening.
- ARV treatment naive (no exposure to ARVs for treatment; could have received ARVs for prophylaxis or prevention of perinatal transmission)
- If an infant had received nevirapine (NVP) as prophylaxis to prevent perinatal transmission, he or she did not receive NVP for at least 14 days prior to enrollment into Stage I or II.
- HIV-1 RNA viral load greater than 1,000 copies/mL of plasma at screening.
- Demonstrated ability or willingness to swallow assigned study medications.
- Parent or legal guardian were able and willing to provide signed informed consent.
- Female participants of reproductive potential, defined as having reached menarche, and who were engaging in sexual activity that could lead to pregnancy, agreed to use two contraceptive methods while on study and for two weeks after stopping study drug.
- Males engaging in sexual activity that could lead to HIV-1 transmission agreed to use a condom.
- Agreed to stay on optimized background therapy (OBT) while on study:
- Participants who at screening were greater than or equal to 2 years of age and ARV-treatment experienced, had at screening at least one fully active drug for the OBT.
- Participants who were greater than or equal to 2 years of age and ARV-treatment naïve, had genotype testing at screening/entry even with results pending.
- Participants less than 2 years of age (either ARV-treatment experienced or ARV treatment naïve), had genotype testing at screening/entry even with results pending.
Who cannot join
- Presence of any active AIDS-defining opportunistic infection
- At enrollment, participant less than 3.0 kg
- Known Grade 3 or greater of any of the following laboratory toxicities within 30 days prior to study entry: neutrophil count, hemoglobin, platelets, aspartate aminotransferase (AST), alanine transaminase (ALT), lipase, serum creatinine and total bilirubin. A single repeat within the 30 days is allowed for eligibility determination. NOTE: Grade 3 total bilirubin was allowable, if the participant was on atazanavir (ATV).
- ANY known Grade 4 laboratory toxicities within 30 days prior to study entry. NOTE: Grade 4 total bilirubin was allowable, if the participant was on ATV.
- The following liver toxicities within 30 days prior to study entry: ALT greater than 3x the upper limit of normal (ULN) AND direct bilirubin was greater than 2x ULN
- Any prior history of malignancy, with the exception of localized malignancies such as squamous cell or basal cell carcinoma of the skin
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- Clinical or symptomatic evidence of pancreatitis, as determined by the clinician
- Use of any disallowed medications at time of screening (see the protocol for a complete list of disallowed medications)
- Known history of exposure to integrase inhibitor treatment by the participant or participant's mother prior to delivery/cessation of breastfeeding
- Known resistance to an integrase inhibitor
- Women who were pregnant or breastfeeding
- At screening/entry, participating in or had participated in a study with a compound or device that was not commercially available within 30 days of signing informed consent, unless permission from both Protocol Teams was granted
- Participant was unlikely to adhere to the study procedures, keep appointments, or was planning to relocate during the study to a non-IMPAACT study site
- Any clinically significant diseases (other than HIV infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator's opinion, would compromise the outcome of this study
- At screening/entry had used, or anticipated using, chronic systemic immunosuppressive agents or systemic interferon (e.g., for treatment of hepatitis C virus [HCV] infection) within 30 days prior to beginning DTG study treatment. Systemic corticosteroids (e.g., prednisone or equivalent up to 2 mg/kg/day) for replacement therapy or short courses (less than or equal to 30 days) were permitted. (See protocol for more information on disallowed medications.)
- Any condition that in the opinion of the site investigator, placed the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol.
- Active tuberculosis (TB) disease and/or requirement for treatment that included rifampin at the time of the screening visit. However, participants who needed rifampin treatment while on DTG were allowed to continue in P1093 provided the DTG dose was adjusted according to the protocol.
Trial locations and contacts
33 sites in 8 countries.
33 sites in 8 countries
United States17 sites
Univ. of Colorado Denver NICHD CRS (Site ID: 5052)
Aurora, Colorado, 80045
Children's Hosp. of Boston NICHD CRS (Site ID: 5009)
Boston, Massachusetts, 02115
Boston Medical Center Ped. HIV Program NICHD CRS (Site ID: 5011)
Boston, Massachusetts, 02118
Rush Univ. Cook County Hosp. Chicago NICHD CRS (Site ID: 5083)
Chicago, Illinois, 60612
Lurie Children's Hospital of Chicago (LCH) CRS (Site ID: 4001)
Chicago, Illinois, 60614-3393
DUMC Ped. CRS (Site ID: 4701)
Durham, North Carolina, 27710
South Florida CDTC Ft Lauderdale NICHD CRS (Site ID: 5055)
Fort Lauderdale, Florida, 33316
University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program (Site ID: 4601)
La Jolla, California, 92093-0672
Miller Children's Hosp. Long Beach CA NICHD CRS (Site ID: 5093)
Long Beach, California, 90806
David Geffen School of Medicine at UCLA NICHD CRS (Site ID: 5112)
Los Angeles, California, 90095-1752
Metropolitan Hosp. NICHD CRS (Site ID: 5003)
New York, New York, 10029
Univ. of California San Francisco NICHD CRS (Site ID: 5091)
San Francisco, California, 94143
Seattle Children's Research Institute CRS (Site ID: 5017)
Seattle, Washington, 98101
USF - Tampa NICHD CRS (Site ID: 5018)
Tampa, Florida, 33606
Bronx-Lebanon Hospital Center NICHD CRS (Site ID: 5114)
The Bronx, New York, 10457
Jacobi Med. Ctr. Bronx NICHD CRS (Site ID: 5013)
The Bronx, New York, 10461
Howard Univ. Washington DC NICHD CRS (Site ID: 5044)
Washington D.C., District of Columbia, 20060
Brazil5 sites
SOM Federal University Minas Gerais Brazil NICHD CRS (Site ID: 5073)
Belo Horizonte, Minas Gerais, 30.130-100
Hospital Federal dos Servidores do Estado NICHD CRS (Site ID: 5072)
Rio de Janeiro, 20221-903
Instituto de Puericultura e Pediatria Martagao Gesteira - UFRJ NICHD CRS (Site ID: 5071)
Rio de Janeiro, 21941-612
Hosp. Geral De Nova Igaucu Brazil NICHD CRS (Site ID: 5097)
Rio de Janeiro, 26030
Univ. of Sao Paulo Brazil NICHD CRS (Site ID: 5074)
São Paulo, 14049-900
South Africa3 sites
Umlazi CRS (Site ID: 30300)
Durban, KwaZulu-Natal, 4001
Wits RHI Shandukani Research Centre CRS (Site ID: 8051)
Johannesburg, Gauteng, 2001
FAMCRU CRS (Site ID: 8950)
Tygerberg, Western Cape, 7505
Thailand3 sites
Siriraj Hospital, Mahidol University NICHD CRS (Site ID: 5115)
Bangkok, Bangkoknoi, 10700
Chiangrai Prachanukroh Hospital NICHD CRS (Site ID: 5116)
Chiang Mai, 50100
Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS (Site ID: 31784)
Chiang Mai, 50200
Botswana2 sites
Gaborone CRS (Site ID: 12701)
Gaborone, South-East District
Molepolole CRS (Site ID: 12702)
Gaborone
Kenya1 site
Kenya Medical Research Institute / Walter Reed Project Clinical Research Center, Kericho CRS (Site ID: 5121)
Kericho, 20200
Tanzania1 site
Kilimanjaro Christian Medical Centre (KCMC) (Site ID: 5118)
Moshi
About this study
Official title: Phase I/II, Multi-Center, Open-Label Pharmacokinetic, Safety, Tolerability and Antiviral Activity of Dolutegravir, a Novel Integrase Inhibitor, in Combination Regimens in HIV-1 Infected Infants, Children and Adolescents
Dolutegravir (DTG) is an HIV drug in the integrase inhibitor drug class. This study evaluated the pharmacokinetics (PK), safety, tolerability of and immune response to DTG when used concurrently with optimized background therapy (OBT) in HIV-1 infected infants, children, and adolescents.
Read the detailed description
DTG is an HIV medicine in the integrase inhibitor drug class. The purpose of this study was to evaluate the pharmacokinetics, safety, tolerability, and antiviral activity of DTG when used concurrently with OBT in HIV-1 infected infants, children, and adolescents.
Participants in this study were evaluated for PK, safety and tolerability through 48 weeks, followed by additional long-term study follow-up that lasted for approximately 144 weeks (3 years), for a total of 192 weeks on study. This study had two stages. Stage I provided pharmacokinetics, short-term tolerability and safety data on DTG on a limited number of participants to permit dose selection for further study in Stage II. Once a Stage I dose was accepted, enrollment to Stage II began to complete enrollment to the cohort. Stage II provided longer-term safety and antiviral activity data among a larger number of participants.
Infants, children and adolescents with HIV-1, aged ≥ 4 weeks to < 18 years enrolled in the age and formulation cohorts specified below:
- Cohort I: Adolescents ≥ 12 to <18 years of age (film-coated tablets)
- Cohort IIA: Children ≥ 6 to <12 years of age (film-coated tablets)
- Cohort IIB: Children ≥ 6 to <12 years of age (granules for suspension)
- Cohort III: Children ≥ 2 to < 6 years of age (granules for suspension)
- Cohort IV: Children ≥ 6 months to < 2 years of age (granules for suspension)
- Cohort III-DT: Children ≥ 2 to < 6 years of age (dispersible tablets)
- Cohort IV-DT: Children ≥ 6 months to < 2 years of age (dispersible tablets)
- Cohort V-DT: Infants ≥ 4 weeks to < 6 months (dispersible tablets)
Cohorts were opened sequentially according by age group (starting with the older age group), DTG formulation, and study stage, i.e. Initial study enrollment was for Cohort I and progressed to Cohort IIA once Cohort I Stage I met the PK and safety criteria, followed by opening of Cohort IIB. Each cohort enrolled in two sequential stages: Stage I and II (the only exception is Cohort IIB, which only enrolled through Stage I). Sequential enrollment for Cohort III and IV proceeded in the same manner. Cohort V never enrolled because of the recommended changes in dosing and inclusion of enrollment weight band in the criteria for dose finding.
Stage I participants had physical examinations and had blood draws for safety assessments at study visits: Day 0; Day 5 (+5 days); and Weeks 4, 8, 12, 16, 24, 32, 40, and 48. Stage I participants also had intensive PK sampling with blood samples collected at time 0 (pre-dose), and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing. Once a Stage I treatment dose was accepted, enrollment to Stage II began to complete enrollment to the cohort. Stage II participants had physical examinations and blood draws for safety assessment at study visits: Day 0; Day 10; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48. Blood, plasma, and urine were collected and tested to measure immune response. Females of childbearing potential underwent pregnancy testing at screening and at every study visit.
After 48 weeks, all Stage I and Stage II participants entered the long-term study follow-up and continued to receive DTG. During this time, participants had safety and/or antiviral activity assessments every 12 weeks for up to 3 years.
The study was able to determine a proposed dose (i.e. optimal dose) for Cohorts I, IIA, III-DT, IV-DT, and V-DT but not for Cohorts IIB, III, and IV. Participants on the proposed dose had intensive PK sampling between days 5 and10 of DTG initiation with blood samples collected at time 0 (pre-dose), and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing.
The study is closed to accrual and study follow-up was completed on Oct 18, 2023.
- Conditions
- HIV Infections
- Being tested
- DTG film-coated tablets, DTG granules for suspension, DTG dispersible tablets
- Keywords
- Integrase Inhibitors, Infant, Child, Adolescent
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DTG film-coated tabletsDrug
DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily. Participants weighing ≥ 35kg received the proposed dose of 50 mg of DTG film-coated tablets.
DTG granules for suspensionDrug
DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.
DTG dispersible tabletsDrug
DTG dispersible tablets initial starting dose of ~0.8 mg/kg with a maximum dose of 30 mg; orally once daily. The proposed weight-band dosing was:
Weight band 3 to <6 kg: 5 mg DTG dispersible tablets; Weight band 6 to <10 kg: 15 mg DTG dispersible tablets; Weight band 10 to <14 kg: 20 mg DTG dispersible tablets; Weight band 14 to <20 kg: 25 mg DTG dispersible tablets; Weight band ≥20 kg: 30 mg DTG dispersible tablets.
DTG dispersible tabletsDrug
DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily. The proposed weight-band dosing was:
Weight band 3 to <6 kg: 5 mg DTG dispersible tablets; Weight band 6 to <10 kg: 15 mg DTG dispersible tablets; Weight band 10 to <14 kg: 20 mg DTG dispersible tablets; Weight band 14 to <20 kg: 25 mg DTG dispersible tablets; Weight band ≥20 kg: 30 mg DTG dispersible tablets.
DTG dispersible tabletsDrug
DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily. The proposed weight-band dosing was:
Weight band 3 to <6 kg: 5 mg DTG dispersible tablets; Weight band 6 to <10 kg: 15 mg DTG dispersible tablets.
| Study group | Role | What they receive |
|---|---|---|
| Cohort I | Experimental | Adolescents 12 to younger than 18 years of age who received DTG film-coated tablets Receives: Drug: DTG film-coated tablets |
| Cohort IIA | Experimental | Children 6 to younger than 12 years of age who received DTG film-coated tablets Receives: Drug: DTG film-coated tablets |
| Cohort IIB | Experimental | Children 6 to younger than 12 years of age who received DTG granules for suspension Receives: Drug: DTG granules for suspension |
| Cohort III | Experimental | Children 2 to younger than 6 years of age who received DTG granules for suspension Receives: Drug: DTG granules for suspension |
| Cohort IV | Experimental | Children 6 months to younger than 2 years of age who received DTG granules for suspension Receives: Drug: DTG granules for suspension |
| Cohort III-DT | Experimental | Children 2 to younger than 6 years of age who received DTG dispersible tablets Receives: Drug: DTG dispersible tablets |
| Cohort IV-DT | Experimental | Children 6 months to younger than 2 years of age who received DTG dispersible tablets Receives: Drug: DTG dispersible tablets |
| Cohort V-DT | Experimental | Infants 4 weeks to younger than 6 months of age who received DTG dispersible tablets Receives: Drug: DTG dispersible tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Grade 3 or Higher Adverse Events (AEs)
All grade 3 or higher signs/symptoms, diagnoses, and laboratory AEs were included.
AE grading was based on DAIDS AE Grading Table, Version 1.0, December 2004 (Clarification, August 2009).
A 2-sided 95% Confidence Interval (CI) was calculated for the percentage using the binominal exact method.
Measured: From treatment initiation through Weeks 24 and 48
Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug
All grade 3 or higher signs/symptoms, diagnoses, and laboratory AEs were included.
AE grading was based on DAIDS AE Grading Table, Version 1.0, December 2004 (Clarification, August 2009).
A 2-sided 95% Confidence Interval (CI) was calculated for the percentage using the binominal exact method.
Measured: From treatment initiation through Weeks 24 and 48
Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug
Number of participants with permanent discontinuation of study drug due to AEs assessed by the site investigator as related to the study drug.
Measured: From treatment initiation through Weeks 24 and 48
Number of Participants Who Died
Number of participants who died were summarized
Measured: From treatment initiation through Weeks 24 and 48
PK Parameter: Area-under-the-curve From 0 to 24 Hours (AUC0-24)
Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). AUC0-24 was determined using linear up-log down estimation in WinNonlin.
Measured: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
Secondary outcomes (25)
Percentage of Participants With Grade 3 or Higher Adverse Events (AEs)
Percentage and exact 95% Confidence Interval (CI) of participants with Grade 3 or higher AEs. AEs were graded based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004, Clarification August 2009 (see References). All grade 3 or higher signs, symptoms, and laboratory toxicities were included.
Measured: From treatment initiation through Week 192. AEs after that time were censored.
Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug
Percentage and exact 95% Confidence Interval (CI) of participants with Grade 3 or higher AEs assessed by the site investigator as related to the study drug.
Measured: From treatment initiation through Week 192. AEs after that time were censored.
Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug
Number of participants with permanent discontinuation of study drug due to AEs assessed by the site investigator as related to the study drug.
Measured: From treatment initiation through Week 192. AEs after that time were censored.
Number of Participants Who Died
Number of participants who died were summarized.
Measured: From treatment initiation through Week 192. AEs after that time were censored.
Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml
Virologic responses were assessed at weeks 24 and 48 as percentages of participants and exact 95% Confidence Interval (CI). The virologic response or virologic failure was defined and calculated according to FDA's Snapshot algorithm.
Measured: Week 24 and Week 48
Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml
Virologic responses were assessed at weeks 24 and 48 as percentages of participants and exact 95% Confidence Interval (CI), The virologic response or virologic failure was defined and calculated according to FDA's Snapshot algorithm.
Measured: Week 24 and Week 48
PK Parameter: Plasma Concentration Observed at End of 24 Hour Dosing Interval (C24h)
Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). C24h was taken directly from the observed concentration-time data or estimated using the elimination rate constant.
Measured: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
PK Parameter: Plasma Concentration Observed Immediately to Dosing of 24 Hour Dosing Interval (C0h)
Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). C0h was taken directly from the observed concentration-time data.
Measured: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
PK Parameter: Minimum Plasma Concentration (Cmin)
Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ) and were performed in real-time. Cmin was taken directly from the observed concentration-time data.
Measured: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
PK Parameter: Maximum Plasma Concentration (Cmax)
Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). Cmax was taken directly from the observed concentration-time data.
Measured: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
PK Parameter: Apparent Clearance (CL/F)
Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). CL/F was calculated as Dose/AUC.
Measured: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
PK Parameter: Apparent Volume of Distribution (Vz/F)
Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). Vz/F was calculated as Dose/(ke x AUC).
Measured: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
PK Parameter: Terminal Half-life (t1/2)
Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). t1/2 was calculated as ln(2)/ke.
Measured: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
Summary of Changes in CD4 Count From Baseline
The median differences between CD4 count at Week 24 and 48 minus at the Day 0 (baseline), and Interquartile Ranges (IQRs) are presented.
Measured: Measured at Day 0, Week 24, and Week 48
Summary of Changes in CD4 Percent From Baseline
The median differences between CD4 percent at Week 24 and 48 minus at the Day 0 (baseline), and Interquartile Ranges (IQRs) are presented.
Measured: Measured at Day 0, Week 24, and Week 48
Summary of Changes in CD8 Count From Baseline
The median differences between CD8 count at Week 24 and 48 minus at the Day 0 (baseline), and Interquartile Ranges (IQRs) are presented.
Measured: Measured at Day 0, Week 24, and Week 48
Summary of Changes in CD8 Percent From Baseline
The median differences between CD8 percent at Week 24 and 48 minus at the Day 0 (baseline), and Interquartile Ranges (IQRs) are presented.
Measured: Measured at Day 0, Week 24, and Week 48
Genotypic Measures of Resistance to Integrase
Genes were sequenced and compared to a reference sequence to identify mutations
Measured: At baseline
Genotypic Measures of Resistance to Integrase
Genes were sequenced and compared to a reference sequence to identify mutations
Measured: at virological failure visit at or prior to Week 192
Genotypic Measures of Resistance to Protease
Genes were sequenced and compared to a reference sequence to identify mutations
Measured: at baseline
Genotypic Measures of Resistance to Protease
Genes were sequenced and compared to a reference sequence to identify mutations
Measured: at virological failures at or prior to Week 192
Genotypic Measures of Resistance to Reverse Transcriptase
Genes were sequenced and compared to a reference sequence to identify mutations
Measured: at baseline
Genotypic Measures of Resistance to Reverse Transcriptase
Genes were sequenced and compared to a reference sequence to identify mutations
Measured: at virologic failure at or prior to Week 192
Phenotypic Measures of Resistance
The participant viral culture is considered to be reduced susceptibility if more DTG is needed to inactivate 50% of the participant viral culture compared to the control viral specimen
Measured: Whenever virological failures took place from baseline to week 192
Worst Case CDC HIV Classification Status
Disease progression as measured by change from baseline to the worst case CDC HIV classification status
Measured: From baseline through Week 192
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2011 (estimated)
- Study start20 Apr 2011
- Primary completion20 Jan 2021
- Study completion18 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 181 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Andrew Wiznia, M.D., Study chair, Jacobi Medical CenterTheodore Ruel, M.D., Study chair, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01302847
- Sponsor's protocol ID
- P1093
- Other IDs
- 11773, 2010-020988-20, IMPAACT P1093
- Status last verified
- Oct 2024
- First submitted
- 15 Feb 2011
- Last updated
- 12 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Bennetto-Hood C, Tabolt G, Savina P, Acosta EP. A sensitive HPLC-MS/MS method for the determination of dolutegravir in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Jan 15;945-946:225-32. doi: 10.1016/j.jchromb.2013.11.054. Epub 2013 Dec 3.
PubMed 24361860Viani RM, Alvero C, Fenton T, Acosta EP, Hazra R, Townley E, Steimers D, Min S, Wiznia A; P1093 Study Team. Safety, Pharmacokinetics and Efficacy of Dolutegravir in Treatment-experienced HIV-1 Infected Adolescents: Forty-eight-week Results from IMPAACT P1093. Pediatr Infect Dis J. 2015 Nov;34(11):1207-13. doi: 10.1097/INF.0000000000000848.
PubMed 26244832Viani RM, Ruel T, Alvero C, Fenton T, Acosta EP, Hazra R, Townley E, Palumbo P, Buchanan AM, Vavro C, Singh R, Graham B, Anthony P, George K, Wiznia A; P1093 Study Team. Long-Term Safety and Efficacy of Dolutegravir in Treatment-Experienced Adolescents With Human Immunodeficiency Virus Infection: Results of the IMPAACT P1093 Study. J Pediatric Infect Dis Soc. 2020 Apr 30;9(2):159-165. doi: 10.1093/jpids/piy139.
PubMed 30951600McKenna M, Lulic Z, Buchanan AM, Brothers C, Tan LK, Wang M, Brummel S, Ziemba L, Ruel T, Flynn PM, Rabie H, Wiznia A. Growth Outcomes After 48 Weeks of Dolutegravir in Children and Adolescents with HIV-1 in IMPAACT P1093 and IMPAACT 2019. J Pediatric Infect Dis Soc. 2026 Sep 12:piag088. doi: 10.1093/jpids/piag088. Online ahead of print.
PubMed 42731017Ruel TD, Acosta EP, Liu JP, Gray KP, George K, Montanez N, Popson S, Buchanan AM, Bartlett M, Dayton D, Anthony P, Brothers C, Vavro C, Singh R, Koech L, Vhembo T, Mmbaga BT, Pinto JA, Dobbels EFM, Archary M, Chokephaibulkit K, Ounchanum P, Deville JG, Hazra R, Townley E, Wiznia A; IMPAACT P1093 team. Pharmacokinetics, safety, tolerability, and antiviral activity of dolutegravir dispersible tablets in infants and children with HIV-1 (IMPAACT P1093): results of an open-label, phase 1-2 trial. Lancet HIV. 2022 May;9(5):e332-e340. doi: 10.1016/S2352-3018(22)00044-3.
PubMed 35489377Singh RP, Adkison KK, Baker M, Parasrampuria R, Wolstenholme A, Davies M, Sewell N, Brothers C, Buchanan AM. Development of Dolutegravir Single-entity and Fixed-dose Combination Formulations for Children. Pediatr Infect Dis J. 2022 Mar 1;41(3):230-237. doi: 10.1097/INF.0000000000003366.
PubMed 34817414Vavro C, Ruel T, Wiznia A, Montanez N, Nangle K, Horton J, Buchanan AM, Stewart EL, Palumbo P. Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Antimicrob Agents Chemother. 2022 Jan 18;66(1):e0164521. doi: 10.1128/AAC.01645-21. Epub 2021 Oct 25.
PubMed 34694878
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II, Multi-Center, Open-Label Pharmacokinetic, Safety, Tolerability and Antiviral Activity of Dolutegravir, a Novel Integrase Inhibitor, in Combination Regimens in HIV-1 Infected Infants, Children and Adolescents
- ClinicalTrials.gov ID
- NCT01302847
- Acronym / sponsor ID
- P1093
- Conditions
- HIV Infections
- Keywords
- Integrase Inhibitors, Infant, Child, Adolescent
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 181 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 20 Apr 2011 (actual)
- Primary completion
- 20 Jan 2021 (actual)
- Study completion
- 18 Oct 2023 (actual)
- First posted
- 24 Feb 2011 (estimated)
- Results
- Posted 22 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Dolutegravir (DTG) is an HIV drug in the integrase inhibitor drug class. This study evaluated the pharmacokinetics (PK), safety, tolerability of and immune response to DTG when used concurrently with optimized background therapy (OBT) in HIV-1 infected infants, children, and adolescents.
Detailed description
DTG is an HIV medicine in the integrase inhibitor drug class. The purpose of this study was to evaluate the pharmacokinetics, safety, tolerability, and antiviral activity of DTG when used concurrently with OBT in HIV-1 infected infants, children, and adolescents.
Participants in this study were evaluated for PK, safety and tolerability through 48 weeks, followed by additional long-term study follow-up that lasted for approximately 144 weeks (3 years), for a total of 192 weeks on study. This study had two stages. Stage I provided pharmacokinetics, short-term tolerability and safety data on DTG on a limited number of participants to permit dose selection for further study in Stage II. Once a Stage I dose was accepted, enrollment to Stage II began to complete enrollment to the cohort. Stage II provided longer-term safety and antiviral activity data among a larger number of participants.
Infants, children and adolescents with HIV-1, aged ≥ 4 weeks to < 18 years enrolled in the age and formulation cohorts specified below:
- Cohort I: Adolescents ≥ 12 to <18 years of age (film-coated tablets)
- Cohort IIA: Children ≥ 6 to <12 years of age (film-coated tablets)
- Cohort IIB: Children ≥ 6 to <12 years of age (granules for suspension)
- Cohort III: Children ≥ 2 to < 6 years of age (granules for suspension)
- Cohort IV: Children ≥ 6 months to < 2 years of age (granules for suspension)
- Cohort III-DT: Children ≥ 2 to < 6 years of age (dispersible tablets)
- Cohort IV-DT: Children ≥ 6 months to < 2 years of age (dispersible tablets)
- Cohort V-DT: Infants ≥ 4 weeks to < 6 months (dispersible tablets)
Cohorts were opened sequentially according by age group (starting with the older age group), DTG formulation, and study stage, i.e. Initial study enrollment was for Cohort I and progressed to Cohort IIA once Cohort I Stage I met the PK and safety criteria, followed by opening of Cohort IIB. Each cohort enrolled in two sequential stages: Stage I and II (the only exception is Cohort IIB, which only enrolled through Stage I). Sequential enrollment for Cohort III and IV proceeded in the same manner. Cohort V never enrolled because of the recommended changes in dosing and inclusion of enrollment weight band in the criteria for dose finding.
Stage I participants had physical examinations and had blood draws for safety assessments at study visits: Day 0; Day 5 (+5 days); and Weeks 4, 8, 12, 16, 24, 32, 40, and 48. Stage I participants also had intensive PK sampling with blood samples collected at time 0 (pre-dose), and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing. Once a Stage I treatment dose was accepted, enrollment to Stage II began to complete enrollment to the cohort. Stage II participants had physical examinations and blood draws for safety assessment at study visits: Day 0; Day 10; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48. Blood, plasma, and urine were collected and tested to measure immune response. Females of childbearing potential underwent pregnancy testing at screening and at every study visit.
After 48 weeks, all Stage I and Stage II participants entered the long-term study follow-up and continued to receive DTG. During this time, participants had safety and/or antiviral activity assessments every 12 weeks for up to 3 years.
The study was able to determine a proposed dose (i.e. optimal dose) for Cohorts I, IIA, III-DT, IV-DT, and V-DT but not for Cohorts IIB, III, and IV. Participants on the proposed dose had intensive PK sampling between days 5 and10 of DTG initiation with blood samples collected at time 0 (pre-dose), and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing.
The study is closed to accrual and study follow-up was completed on Oct 18, 2023.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Cohort I | Experimental | Drug: DTG film-coated tabletsAdolescents 12 to younger than 18 years of age who received DTG film-coated tablets |
| Cohort IIA | Experimental | Drug: DTG film-coated tabletsChildren 6 to younger than 12 years of age who received DTG film-coated tablets |
| Cohort IIB | Experimental | Drug: DTG granules for suspensionChildren 6 to younger than 12 years of age who received DTG granules for suspension |
| Cohort III | Experimental | Drug: DTG granules for suspensionChildren 2 to younger than 6 years of age who received DTG granules for suspension |
| Cohort IV | Experimental | Drug: DTG granules for suspensionChildren 6 months to younger than 2 years of age who received DTG granules for suspension |
| Cohort III-DT | Experimental | Drug: DTG dispersible tabletsChildren 2 to younger than 6 years of age who received DTG dispersible tablets |
| Cohort IV-DT | Experimental | Drug: DTG dispersible tabletsChildren 6 months to younger than 2 years of age who received DTG dispersible tablets |
| Cohort V-DT | Experimental | Drug: DTG dispersible tabletsInfants 4 weeks to younger than 6 months of age who received DTG dispersible tablets |
Who may qualify
- Ages
- 4 weeks to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (19 listed)
- Confirmed HIV-1 infection, defined as positive results from two samples collected at different time points (see protocol for more information)
- Participant belonged to one of the ARV exposure groups below:
- If an infant had received nevirapine (NVP) as prophylaxis to prevent perinatal transmission, he or she did not receive NVP for at least 14 days prior to enrollment into Stage I or II.
- HIV-1 RNA viral load greater than 1,000 copies/mL of plasma at screening.
- Demonstrated ability or willingness to swallow assigned study medications.
Key exclusion criteria (17 listed)
- Presence of any active AIDS-defining opportunistic infection
- At enrollment, participant less than 3.0 kg
- Known Grade 3 or greater of any of the following laboratory toxicities within 30 days prior to study entry: neutrophil count, hemoglobin, platelets, aspartate aminotransferase (AST), alanine transaminase (ALT), lipase, serum creatinine and total bilirubin. A single repeat within the 30 days is allowed for eligibility determination. NOTE: Grade 3 total bilirubin was allowable, if the participant was on atazanavir (ATV).
- ANY known Grade 4 laboratory toxicities within 30 days prior to study entry. NOTE: Grade 4 total bilirubin was allowable, if the participant was on ATV.
- The following liver toxicities within 30 days prior to study entry: ALT greater than 3x the upper limit of normal (ULN) AND direct bilirubin was greater than 2x ULN
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 |
|---|---|---|
| DTG film-coated tabletsDTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily. Participants weighing ≥ 35kg received the proposed dose of 50 mg of DTG film-coated tablets. | Drug | Cohort I, Cohort IIA |
| DTG granules for suspensionDTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily. | Drug | Cohort IIB, Cohort III, Cohort IV |
| DTG dispersible tabletsDTG dispersible tablets initial starting dose of ~0.8 mg/kg with a maximum dose of 30 mg; orally once daily. The proposed weight-band dosing was: Weight band 3 to <6 kg: 5 mg DTG dispersible tablets; Weight band 6 to <10 kg: 15 mg DTG dispersible tablets; Weight band 10 to <14 kg: 20 mg DTG dispersible tablets; Weight band 14 to <20 kg: 25 mg DTG dispersible tablets; Weight band ≥20 kg: 30 mg DTG dispersible tablets. | Drug | Cohort III-DT |
| DTG dispersible tabletsDTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily. The proposed weight-band dosing was: Weight band 3 to <6 kg: 5 mg DTG dispersible tablets; Weight band 6 to <10 kg: 15 mg DTG dispersible tablets; Weight band 10 to <14 kg: 20 mg DTG dispersible tablets; Weight band 14 to <20 kg: 25 mg DTG dispersible tablets; Weight band ≥20 kg: 30 mg DTG dispersible tablets. | Drug | Cohort IV-DT |
| DTG dispersible tabletsDTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily. The proposed weight-band dosing was: Weight band 3 to <6 kg: 5 mg DTG dispersible tablets; Weight band 6 to <10 kg: 15 mg DTG dispersible tablets. | Drug | Cohort V-DT |
Primary outcome
Percentage of Participants With Grade 3 or Higher Adverse Events (AEs)
Time frame: From treatment initiation through Weeks 24 and 48
All grade 3 or higher signs/symptoms, diagnoses, and laboratory AEs were included. AE grading was based on DAIDS AE Grading Table, Version 1.0, December 2004 (Clarification, August 2009). A 2-sided 95% Confidence Interval (CI) was calculated for the percentage using the binominal exact method.
Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug
Time frame: From treatment initiation through Weeks 24 and 48
All grade 3 or higher signs/symptoms, diagnoses, and laboratory AEs were included. AE grading was based on DAIDS AE Grading Table, Version 1.0, December 2004 (Clarification, August 2009). A 2-sided 95% Confidence Interval (CI) was calculated for the percentage using the binominal exact method.
Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug
Time frame: From treatment initiation through Weeks 24 and 48
Number of participants with permanent discontinuation of study drug due to AEs assessed by the site investigator as related to the study drug.
Number of Participants Who Died
Time frame: From treatment initiation through Weeks 24 and 48
Number of participants who died were summarized
PK Parameter: Area-under-the-curve From 0 to 24 Hours (AUC0-24)
Time frame: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). AUC0-24 was determined using linear up-log down estimation in WinNonlin.
25 secondary outcomes
Percentage of Participants With Grade 3 or Higher Adverse Events (AEs)
Time frame: From treatment initiation through Week 192. AEs after that time were censored.
Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug
Time frame: From treatment initiation through Week 192. AEs after that time were censored.
Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug
Time frame: From treatment initiation through Week 192. AEs after that time were censored.
Number of Participants Who Died
Time frame: From treatment initiation through Week 192. AEs after that time were censored.
Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml
Time frame: Week 24 and Week 48
Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml
Time frame: Week 24 and Week 48
PK Parameter: Plasma Concentration Observed at End of 24 Hour Dosing Interval (C24h)
Time frame: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
PK Parameter: Plasma Concentration Observed Immediately to Dosing of 24 Hour Dosing Interval (C0h)
Time frame: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
PK Parameter: Minimum Plasma Concentration (Cmin)
Time frame: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
PK Parameter: Maximum Plasma Concentration (Cmax)
Time frame: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
PK Parameter: Apparent Clearance (CL/F)
Time frame: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
PK Parameter: Apparent Volume of Distribution (Vz/F)
Time frame: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
PK Parameter: Terminal Half-life (t1/2)
Time frame: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
Summary of Changes in CD4 Count From Baseline
Time frame: Measured at Day 0, Week 24, and Week 48
Summary of Changes in CD4 Percent From Baseline
Time frame: Measured at Day 0, Week 24, and Week 48
Summary of Changes in CD8 Count From Baseline
Time frame: Measured at Day 0, Week 24, and Week 48
Summary of Changes in CD8 Percent From Baseline
Time frame: Measured at Day 0, Week 24, and Week 48
Genotypic Measures of Resistance to Integrase
Time frame: At baseline
Genotypic Measures of Resistance to Integrase
Time frame: at virological failure visit at or prior to Week 192
Genotypic Measures of Resistance to Protease
Time frame: at baseline
Genotypic Measures of Resistance to Protease
Time frame: at virological failures at or prior to Week 192
Genotypic Measures of Resistance to Reverse Transcriptase
Time frame: at baseline
Genotypic Measures of Resistance to Reverse Transcriptase
Time frame: at virologic failure at or prior to Week 192
Phenotypic Measures of Resistance
Time frame: Whenever virological failures took place from baseline to week 192
Worst Case CDC HIV Classification Status
Time frame: From baseline through Week 192
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24361860Bennetto-Hood C, Tabolt G, Savina P, Acosta EP. A sensitive HPLC-MS/MS method for the determination of dolutegravir in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Jan 15;945-946:225-32. doi: 10.1016/j.jchromb.2013.11.054. Epub 2013 Dec 3.
- Background: PubMed 26244832Viani RM, Alvero C, Fenton T, Acosta EP, Hazra R, Townley E, Steimers D, Min S, Wiznia A; P1093 Study Team. Safety, Pharmacokinetics and Efficacy of Dolutegravir in Treatment-experienced HIV-1 Infected Adolescents: Forty-eight-week Results from IMPAACT P1093. Pediatr Infect Dis J. 2015 Nov;34(11):1207-13. doi: 10.1097/INF.0000000000000848.
- Background: PubMed 30951600Viani RM, Ruel T, Alvero C, Fenton T, Acosta EP, Hazra R, Townley E, Palumbo P, Buchanan AM, Vavro C, Singh R, Graham B, Anthony P, George K, Wiznia A; P1093 Study Team. Long-Term Safety and Efficacy of Dolutegravir in Treatment-Experienced Adolescents With Human Immunodeficiency Virus Infection: Results of the IMPAACT P1093 Study. J Pediatric Infect Dis Soc. 2020 Apr 30;9(2):159-165. doi: 10.1093/jpids/piy139.
- Derived from this study: PubMed 42731017McKenna M, Lulic Z, Buchanan AM, Brothers C, Tan LK, Wang M, Brummel S, Ziemba L, Ruel T, Flynn PM, Rabie H, Wiznia A. Growth Outcomes After 48 Weeks of Dolutegravir in Children and Adolescents with HIV-1 in IMPAACT P1093 and IMPAACT 2019. J Pediatric Infect Dis Soc. 2026 Sep 12:piag088. doi: 10.1093/jpids/piag088. Online ahead of print.
- Derived from this study: PubMed 35489377Ruel TD, Acosta EP, Liu JP, Gray KP, George K, Montanez N, Popson S, Buchanan AM, Bartlett M, Dayton D, Anthony P, Brothers C, Vavro C, Singh R, Koech L, Vhembo T, Mmbaga BT, Pinto JA, Dobbels EFM, Archary M, Chokephaibulkit K, Ounchanum P, Deville JG, Hazra R, Townley E, Wiznia A; IMPAACT P1093 team. Pharmacokinetics, safety, tolerability, and antiviral activity of dolutegravir dispersible tablets in infants and children with HIV-1 (IMPAACT P1093): results of an open-label, phase 1-2 trial. Lancet HIV. 2022 May;9(5):e332-e340. doi: 10.1016/S2352-3018(22)00044-3.
- Derived from this study: PubMed 34817414Singh RP, Adkison KK, Baker M, Parasrampuria R, Wolstenholme A, Davies M, Sewell N, Brothers C, Buchanan AM. Development of Dolutegravir Single-entity and Fixed-dose Combination Formulations for Children. Pediatr Infect Dis J. 2022 Mar 1;41(3):230-237. doi: 10.1097/INF.0000000000003366.
- Derived from this study: PubMed 34694878Vavro C, Ruel T, Wiznia A, Montanez N, Nangle K, Horton J, Buchanan AM, Stewart EL, Palumbo P. Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Antimicrob Agents Chemother. 2022 Jan 18;66(1):e0164521. doi: 10.1128/AAC.01645-21. Epub 2021 Oct 25.
- The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009).Link provided by the sponsor.
- Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010Link 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.
Andrew Wiznia, M.D. study chair
Jacobi Medical Center
Theodore Ruel, M.D. study chair
University of California, San Francisco
33 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing DTG film-coated tablets, DTG granules for suspension and DTG dispersible tablets in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 33 sites in 8 countries.
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 19 inclusion and 17 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 12 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in United States, Brazil, South Africa, Thailand, Botswana and 3 more countries. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) (time frame: From treatment initiation through Weeks 24 and 48). The study lists 5 primary outcomes in all. 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 NCT01302847, which also lists 7 linked publications.
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 12 Dec 2024.