Phase 1
Completed N=33
A Food-effect Study of the Pediatric Dispersible Tablet Formulations of TRIUMEQ® and DOVATO® in Healthy Adult Participants
Source: ClinicalTrials.gov NCT04827134 ↗Enrolled (actual)
33
Serious AEs
0.0%
Results posted
Jun 2023
Primary outcomePrimary: Cohort 1: Area Under the Plasma Concentration-time Curve (AUC) From Time Zero Extrapolated to Infinity (AUC [0-inf]) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions — 59140; 67210; 8565; 9986 Hours*nanogram per milliliter
Summary
This study will assess the effect of food on the pharmacokinetics (PK) of pediatric formulations of TRIUMEQ (dolutegravir [DTG] 5 milligrams [mg]/abacavir [ABC] 60 mg/lamivudine [3TC] 30 mg) dispersible tablets and DOVATO (DTG 5 mg/3TC 30 mg) dispersible tablets in healthy adult participants. Additionally, safety and tolerability of these formulations will also be assessed. TRIUMEQ and DOVATO are registered trademarks of GlaxoSmithKline group of companies.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cohort 1: Area Under the Plasma Concentration-time Curve (AUC) From Time Zero Extrapolated to Infinity (AUC [0-inf]) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions |
59140; 67210; 8565; 9986; 6508; 7295 | — |
| PRIMARY Cohort 1: AUC From Time Zero to Time of Last Observed Quantifiable Concentration (AUC [0-t]) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions |
55770; 63790; 8501; 9923; 6319; 7182 | — |
| PRIMARY Cohort 1: Maximum Observed Concentration (Cmax) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions |
2359; 3322; 1837; 4080; 886.9; 1392 | — |
| PRIMARY Cohort 2: AUC (0-inf) of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions |
47830; 51800; 6975; 7864 | — |
| PRIMARY Cohort 2: AUC (0-t) of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions |
46060; 49690; 6799; 7762 | — |
| PRIMARY Cohort 2: Cmax of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions |
2331; 3131; 1084; 2066 | — |
| SECONDARY Cohort 1: Lag Time for Absorption (Tlag) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions |
0.000; 0.000; 0.000; 0.000; 0.000; 0.000 | — |
| SECONDARY Cohort 1: Terminal Elimination Phase Half-life (t1/2) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions |
16.18; 16.10; 2.291; 1.958; 17.35; 15.23 | — |
| SECONDARY Cohort 1: AUC From Time Zero to 24 Hours (AUC[0-24]) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions |
36380; 43870; 8553; 9980; 5817; 6707 | — |
| SECONDARY Cohort 1: Last Quantifiable Concentration (Ct) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions |
122.2; 128.6; 10.61; 17.51; 5.280; 4.621 | — |
| SECONDARY Cohort 1: Concentration at 24 Hours Post-dose (C24) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions |
958.6; 996.3; 4.833; 3.814; 23.40; 21.74 | — |
| SECONDARY Cohort 1: Time of Maximum Observed Concentration (Tmax) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions |
5.000; 1.250; 2.750; 0.500; 3.500; 1.508 | — |
| SECONDARY Cohort 2: Tlag of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions |
0.000; 0.000; 0.000; 0.000 | — |
| SECONDARY Cohort 2: t1/2 of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions |
14.43; 15.12; 18.47; 18.36 | — |
| SECONDARY Cohort 2: AUC(0-24) of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions |
32620; 35360; 6339; 7339 | — |
| SECONDARY Cohort 2: Ct of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions |
82.37; 79.73; 4.078; 3.622 | — |
| SECONDARY Cohort 2: C24 of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions |
764.7; 715.4; 22.56; 20.38 | — |
| SECONDARY Cohort 2: Tmax of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions |
4.000; 0.875; 3.000; 0.750 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
1; 3; 1; 1; 0; 0 | — |
| SECONDARY Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count and Neutrophil |
-0.002; -0.004; -0.003; 0.001; -0.002; 0.015 | — |
| SECONDARY Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count |
0.008; -0.006; 0.024; 0.018 | — |
| SECONDARY Change From Baseline in Hematology Parameters: Hemoglobin |
0.3; -1.1; 1.2; -0.1 | — |
| SECONDARY Change From Baseline in Hematology Parameters: Hematocrit |
-0.0001; 0.0003; 0.0006; 0.0010 | — |
| SECONDARY Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Volume |
-0.09; 0.12; -0.28; -0.14 | — |
| SECONDARY Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Hemoglobin |
-0.03; -0.24; 0.13; -0.09 | — |
| SECONDARY Absolute Values of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count and Neutrophil |
0.040; 0.043; 0.042; 0.041; 0.038; 0.039 | — |
| SECONDARY Absolute Values of Hematology Parameters: RBC Count |
4.648; 4.684; 4.765; 4.848; 4.656; 4.678 | — |
| SECONDARY Absolute Values of Hematology Parameters: Hemoglobin |
133.5; 134.4; 142.0; 144.5; 133.8; 133.3 | — |
| SECONDARY Absolute Values of Hematology Parameters: Hematocrit |
0.3957; 0.3976; 0.4163; 0.4227; 0.3956; 0.3979 | — |
| SECONDARY Absolute Values of Hematology Parameters: Erythrocytes Mean Corpuscular Volume |
85.11; 84.92; 87.64; 87.45; 85.02; 85.04 | — |
| SECONDARY Absolute Values of Hematology Parameters: Erythrocytes Mean Corpuscular Hemoglobin |
28.74; 28.71; 29.89; 29.89; 28.71; 28.48 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Parameters: Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Amino Transferase (AST) |
4.0; -5.1; -0.4; -3.6; -2.6; -3.0 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN) |
-0.003; -0.034; 0.029; 0.038; -0.037; -0.169 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Parameters: Creatinine, Direct Bilirubin and Total Bilirubin |
9.18; 10.76; 1.83; 2.11; 0.16; 0.05 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Parameters: Creatine Kinase |
-17.8; -51.9; -33.9; -29.5 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Parameters: Albumin and Total Protein |
0.2; -0.9; 0.9; 1.1; 0.9; -0.2 | — |
| SECONDARY Absolute Values of Clinical Chemistry Parameters: ALT, ALP and AST |
19.7; 24.3; 23.4; 24.8; 23.7; 19.3 | — |
| SECONDARY Absolute Values of Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and BUN |
2.350; 2.376; 2.339; 2.333; 2.347; 2.342 | — |
| SECONDARY Absolute Values of Clinical Chemistry Parameters: Creatinine, Direct Bilirubin and Total Bilirubin |
74.38; 75.10; 80.18; 82.54; 83.55; 85.86 | — |
| SECONDARY Absolute Values of Clinical Chemistry Parameters: Creatine Kinase |
111.5; 143.8; 119.7; 124.6; 93.7; 91.8 | — |
| SECONDARY Absolute Values of Clinical Chemistry Parameters: Albumin and Total Protein |
44.0; 44.5; 43.0; 42.9; 44.2; 43.6 | — |
| SECONDARY Change From Baseline in Urinalysis Parameter: Specific Gravity |
0.0034; 0.0013; 0.0029; 0.0019 | — |
| SECONDARY Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH) by Dipstick |
-0.34; -0.22; -0.13; -0.44 | — |
| SECONDARY Absolute Values of Urinalysis Parameter: Specific Gravity |
1.0128; 1.0134; 1.0151; 1.0163; 1.0162; 1.0147 | — |
| SECONDARY Absolute Values of Urinalysis Parameter: Potential of Hydrogen (pH) by Dipstick |
6.38; 6.22; 6.41; 6.50; 6.03; 6.00 | — |
| SECONDARY Number of Participants With Abnormal Values on Urinalysis by Dipstick |
16; 16; 17; 16; 16; 16 | — |
| SECONDARY Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval and Corrected QT Interval According to Fridericia's Formula (QTcF) |
2.2; -0.7; -2.7; 4.0; -1.2; -2.9 | — |
| SECONDARY Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF |
163.4; 161.6; 174.6; 176.1; 165.6; 160.9 | — |
| SECONDARY Change From Baseline in Vital Signs Measurements: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
-1.1; -4.2; 1.9; 0.6; 0.0; 0.3 | — |
| SECONDARY Absolute Values of Vital Signs Measurements: SBP and DBP |
110.6; 113.0; 112.5; 113.5; 109.5; 108.8 | — |
| SECONDARY Change From Baseline in Vital Signs Measurements: Pulse Rate |
3.0; -0.3; 1.1; -0.1 | — |
| SECONDARY Absolute Values of Vital Signs Measurements: Pulse Rate |
59.9; 62.3; 59.9; 60.1; 62.9; 62.0 | — |
Eligibility Criteria
Inclusion Criteria
- Participant must be 18 to 50 years of age inclusive, at the time of signing the informed consent.
- Participants who are healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (history and ECG).
- Body weight >=50.0 kilograms (kg) (110 pounds [lbs.]) for males and >=45 kg (99 lbs.) for females and body mass index within the range 18.5 to 31.0 kilogram per meter square (kg/m^2, inclusive).
- A male participant is eligible to participate if they agree to use contraceptive methods.
- A female participant is eligible to participate if she is not pregnant (, not lactating or breastfeeding, and at least 1 of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and using a non-hormonal contraceptive method that is highly effective
- Capable of giving signed informed consent
- Documentation that the participant is negative for the human leukocyte antigen (HLA) B*5701 allele.
Exclusion Criteria
- Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Medical history of cardiac arrhythmias, prior myocardial infarction in the past 3 months, or cardiac disease or a family or personal history of long QT syndrome.
- A pre-existing condition interfering with normal gastrointestinal anatomy or motility (e.g., gastroesophageal reflux disease, gastric ulcers, gastritis), hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study intervention.
- QT interval corrected for heart rate according to Fridericia's formula (QTcF) >450 milliseconds (msec).
- A participant with known or suspected active coronavirus disease (COVID-19) infection OR contact with an individual with known COVID-19, within 14 days of study enrollment.
- Presence of hepatitis B surface antigen at screening or within 3 months prior to starting study intervention.
- Positive hepatitis C antibody test result at screening or within 3 months prior to starting study intervention AND positive on reflex to hepatitis C ribonucleic acid (RNA).
- Positive human immunodeficiency virus (HIV)-1 and -2 antigen/antibody immunoassay at screening.
- Alanine aminotransferase (ALT) >1.5 × upper limit of normal (ULN). A single repeat of ALT is allowed within a single screening period to determine eligibility.
- Bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin 14 units for males or >7 drinks for females.
- Unable to refrain from tobacco or nicotine-containing products within 1 month prior to screening.
- History of sensitivity, prior intolerance or hypersensitivity to any of the study interventions, or components thereof, or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.
Data sourced from ClinicalTrials.gov (NCT04827134). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.