Phase 1
Completed N=18
To Assess the Relative Bioavailability (BA) of TRIUMEQ® and Dolutegravir and Lamivudine (DTG/3TC) Pediatric Dispersible Tablet Formulations in Healthy Volunteers
Source: ClinicalTrials.gov NCT03441984 ↗Enrolled (actual)
18
Serious AEs
0.0%
Results posted
Dec 2019
Primary outcomePrimary: Area Under the Plasma Concentration-time Curve (AUC) From Time of Dose Extrapolated to Infinity (AUC[0-inf]) in Part 1 of DTG — 59.761; 101.125; 77.742 Hours*microgram per milliliter
Summary
This is a 2-part, single-dose, open label, randomized 3-way cross-over study to compare BA of pediatric study drugs TRIUMEQ and (DTG/3TC) in healthy volunteers under fasted conditions. Study will be conducted in 2-parts. Each part 1 and part 2 will comprise of 3-treatment periods (TP) where Part 1, will assess BA, of pediatric TRIUMEQ dispersible tablets with an adult TRIUMEQ conventional tablet formulation and Part 2, will assess BA, of pediatric DTG/3TC dispersible tablets with adult DTG and 3TC conventional tablets formulation. Total duration of study is 9-weeks and will be conducted in approximately 36 subjects. The 2-parts, may be run in parallel as they are independent of each other. TRIUMEQ is a registered trademark of GlaxoSmithKline group of companies.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Concentration-time Curve (AUC) From Time of Dose Extrapolated to Infinity (AUC[0-inf]) in Part 1 of DTG |
59.761; 101.125; 77.742 | — |
| PRIMARY AUC From Time of Dose to Last Measurable Concentration (AUC[0-t]) in Part 1 of DTG |
57.571; 97.746; 75.086 | — |
| PRIMARY Maximum Observed Concentration (Cmax) in Part 1 of DTG in Plasma |
3.093; 5.373; 4.134 | — |
| PRIMARY AUC(0-inf) in Part 1 of ABC |
16.636; 17.321; 16.756 | — |
| PRIMARY AUC(0-t) in Part 1 of ABC |
16.609; 17.298; 16.735 | — |
| PRIMARY Cmax in Part 1 of ABC in Plasma |
5.084; 5.351; 4.891 | — |
| PRIMARY AUC(0-inf) in Part 1 of 3TC |
13.087; 13.062; 12.155 | — |
| PRIMARY AUC (0-t) in Part 1 of 3TC |
12.857; 12.829; 11.893 | — |
| PRIMARY Cmax in Part 1 of 3TC |
2.194; 2.053; 1.947 | — |
| PRIMARY AUC(0-inf) in Part 2 of DTG in Plasma |
53.942; 88.676; 68.496 | — |
| PRIMARY AUC(0-t) in Part 2 of DTG |
51.477; 85.340; 65.657 | — |
| PRIMARY Cmax in Part 2 of DTG in Plasma |
2.764; 5.461; 3.558 | — |
| PRIMARY AUC(0-inf) in Part 2 of 3TC |
12.245; 12.149; 11.910 | — |
| PRIMARY AUC(0-t) in Part 2 of 3TC |
11.991; 11.788; 11.633 | — |
| PRIMARY Cmax in Part 2 of 3TC |
2.276; 2.071; 2.093 | — |
| SECONDARY AUC From Time of Dose to 24 Hours (AUC[0-24]) of DTG in Part 1 |
40.264; 69.745; 53.250 | — |
| SECONDARY Time to Maximum Concentration (Tmax) of DTG in Plasma in Part 1 |
3.00; 2.50; 3.00 | — |
| SECONDARY Time of Last Quantifiable Concentration (Tlast) of DTG in Part 1 |
72.00; 72.00; 72.00 | — |
| SECONDARY Apparent Oral Clearance (CL/F) of DTG in Plasma in Part 1 |
0.8367; 0.4944; 0.6432 | — |
| SECONDARY Apparent Volume of Distribution (Vz/F) of DTG in Part 1 |
17.260; 10.074; 12.998 | — |
| SECONDARY Observed Concentration at 24 Hours Postdose (C24) of DTG in Plasma in Part 1 |
925.303; 1523.534; 1198.948 | — |
| SECONDARY Last Observed Quantifiable Concentration (Ct) of DTG in Plasma in Part 1 |
84.968; 138.258; 106.140 | — |
| SECONDARY Terminal Elimination Phase Half-life (t½) of DTG in Plasma in Part 1 |
14.300; 14.123; 14.008 | — |
| SECONDARY Lag Time for Absorption (Tlag) of DTG in Part 1 |
0.00; 0.00; 0.00 | — |
| SECONDARY AUC(0-24) of ABC in Plasma in Part 1 |
16.619; 17.300; 16.743 | — |
| SECONDARY Tmax of ABC in Plasma in Part 1 |
1.50; 1.00; 1.00 | — |
| SECONDARY Tlast of ABC in Part 1 |
24.00; 24.00; 24.00 | — |
| SECONDARY CL/F of ABC in Plasma in Part 1 |
36.0658; 34.6391; 35.8073 | — |
| SECONDARY Vz/F of ABC in Part 1 |
120.412; 126.171; 123.076 | — |
| SECONDARY C24 of ABC in Plasma in Part 1 |
4.862; 4.491; 4.274 | — |
| SECONDARY Ct of ABC in Plasma in Part 1 |
6.852; 4.788; 5.466 | — |
| SECONDARY T½ of ABC in Plasma in Part 1 |
2.314; 2.525; 2.382 | — |
| SECONDARY AUC(0-24) of 3TC in Plasma in Part 1 |
11.968; 11.927; 10.952 | — |
| SECONDARY Tmax of 3TC in Part 1 |
2.50; 2.50; 2.50 | — |
| SECONDARY Tlast of 3TC in Plasma in Part 1 |
72.00; 72.00; 72.00 | — |
| SECONDARY CL/F of 3TC in Plasma in Part 1 |
22.9237; 22.9679; 24.6802 | — |
| SECONDARY Vz/F of 3TC in Plasma in Part 1 |
594.270; 591.102; 642.945 | — |
| SECONDARY C24 of 3TC in Plasma in Part 1 |
37.963; 40.913; 42.434 | — |
| SECONDARY Ct of 3TC in Plasma in Part 1 |
6.552; 6.798; 7.251 | — |
| SECONDARY T½ of 3TC in Plasma in Part 1 |
17.969; 17.839; 18.057 | — |
| SECONDARY AUC (0-24) of DTG in Plasma in Part 2 |
35.742; 61.220; 46.205 | — |
| SECONDARY Tmax of DTG in Plasma in Part 2 |
2.77; 0.77; 1.79 | — |
| SECONDARY Tlast of DTG in Plasma in Part 2 |
72.00; 72.00; 72.00 | — |
| SECONDARY CL/F of DTG in Plasma in Part 2 |
0.9269; 0.5639; 0.7300 | — |
| SECONDARY Vz/F of DTG in Plasma in Part 2 |
20.378; 11.950; 15.524 | — |
| SECONDARY C24 of DTG in Plasma in Part 2 |
825.313; 1289.044; 1034.078 | — |
| SECONDARY Ct of DTG in Plasma in Part 2 |
95.829; 131.216; 107.749 | — |
| SECONDARY T½ of DTG in Plasma in Part 2 |
15.238; 14.690; 14.741 | — |
| SECONDARY Tlag of DTG in Plasma in Part 2 |
0.00; 0.00; 0.00 | — |
| SECONDARY AUC (0-24) of 3TC in Plasma in Part 2 |
11.070; 10.802; 10.673 | — |
| SECONDARY Tmax of 3TC in Plasma in Part 2 |
1.00; 1.50; 1.50 | — |
| SECONDARY Tlast of 3TC in Plasma in Part 2 |
72.00; 72.00; 72.00 | — |
| SECONDARY CL/F of 3TC in Plasma in Part 2 |
24.4998; 24.6933; 25.1888 | — |
| SECONDARY Vz/F of 3TC in Plasma in Part 2 |
730.859; 758.790; 711.280 | — |
| SECONDARY C24 of 3TC in Plasma in Part 2 |
35.808; 38.475; 38.336 | — |
| SECONDARY Ct of 3TC in Plasma in Part 2 |
7.735; 8.417; 7.480 | — |
| SECONDARY T½ of 3TC in Plasma in Part 2 |
20.677; 21.299; 19.573 | — |
| SECONDARY Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) in Part 1 |
1; 1; 2; 0; 0; 0 | — |
| SECONDARY Number of Participants With AEs and Serious Adverse Events SAEs in Part 2 |
1; 0; 1; 0; 0; 0 | — |
| SECONDARY Absolute Values for Clinical Chemistry Parameters Measured in Part 1: Glucose, Calcium, Potassium, Sodium and Urea |
5.031; 4.931; 4.933; 2.377; 2.371; 2.384 | — |
| SECONDARY Absolute Values for Clinical Chemistry Parameters Measured in Part 1: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotranferase (AST) and Creatinine Phosphokinase (CPK) |
15.3; 14.8; 15.3; 54.4; 55.1; 54.4 | — |
| SECONDARY Absolute Values for Clinical Chemistry Parameters Measured in Part 1: Albumin and Protein |
43.2; 42.9; 43.8; 70.7; 70.8; 71.9 | — |
| SECONDARY Absolute Values for Clinical Chemistry Parameters Measured in Part 1: Bilirubin, Creatinine and Direct Bilirubin |
9.58; 9.88; 9.99; 81.47; 82.73; 83.36 | — |
| SECONDARY Absolute Values for Clinical Chemistry Parameters Measured in Part 2: Glucose, Calcium, Potassium, Sodium and Urea |
4.938; 4.941; 4.959; 2.378; 2.367; 2.366 | — |
| SECONDARY Absolute Values for Clinical Chemistry Parameters Measured in Part 2: ALT, ALP, AST and CPK |
16.1; 15.6; 14.9; 60.0; 58.8; 58.9 | — |
| SECONDARY Absolute Values for Clinical Chemistry Parameters Measured in Part 2: Albumin and Protein |
43.9; 43.1; 43.1; 72.1; 70.9; 71.2 | — |
| SECONDARY Absolute Values for Clinical Chemistry Parameters Measured in Part 2: Bilirubin, Creatinine and Direct Bilirubin |
10.71; 10.60; 10.58; 87.66; 87.97; 87.11 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Parameters Measured in Part 1: Glucose, Calcium, Potassium, Sodium and Urea |
0.045; -0.068; -0.115; 0.023; 0.026; 0.026 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Parameters Measured in Part 1: ALT, ALP, AST and CPK |
-0.3; -0.1; -0.9; -2.6; -0.5; -0.2 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Parameters Measured in Part 1: Albumin and Protein |
0.4; -0.3; 0.4; 1.9; 1.6; 2.1 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Parameters Measured in Part 1: Bilirubin, Creatinine and Direct Bilirubin |
1.95; 2.20; 1.63; 13.61; 13.06; 13.62 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: Glucose, Calcium, Potassium, Sodium and Urea |
-0.128; -0.107; -0.175; 0.016; 0.019; -0.004 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: ALT, ALP, AST and CPK |
-1.2; -2.0; -0.9; -1.7; -3.4; -0.7 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: Albumin and Protein |
-0.1; -0.1; -0.6; 1.1; 1.1; 0.6 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: Bilirubin, Creatinine and Direct Bilirubin |
1.84; 1.56; 1.91; 10.08; 10.32; 10.83 | — |
| SECONDARY Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 1 |
0.042; 0.042; 0.037; 0.152; 0.145; 0.144 | — |
| SECONDARY Absolute Values for Erythrocyte Mean Corpuscular Hemoglobin in Part 1 |
83.92; 83.84; 83.97 | — |
| SECONDARY Absolute Values for Erythrocytes in Part 1 |
4.905; 4.884; 4.914 | — |
| SECONDARY Absolute Values for Hemocrit in Part 1 |
0.4101; 0.4076; 0.4114 | — |
| SECONDARY Absolute Values for Hemoglobin in Part 1 |
137.2; 135.9; 138.1 | — |
| SECONDARY Absolute Values for Hematology Parameters Including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 2 |
0.042; 0.044; 0.039; 0.099; 0.099; 0.100 | — |
| SECONDARY Absolute Values for Erythrocyte Mean Corpuscular Hemoglobin in Part 2 |
29.78; 29.79; 29.81 | — |
| SECONDARY Absolute Values for Erythrocyte Mean Corpuscular Volume in Part 2 |
88.43; 88.28; 88.34 | — |
| SECONDARY Absolute Values for Erythrocytes in Part 2 |
4.812; 4.794; 4.776 | — |
| SECONDARY Absolute Values for Hemocrit in Part 2 |
0.4243; 0.4219; 0.4206 | — |
| SECONDARY Absolute Values for Hemoglobin in Part 2 |
143.0; 142.3; 141.8 | — |
| SECONDARY Change From Baseline Values for Hematology Parameters Including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 1 |
-0.009; -0.009; -0.011; -0.013; -0.008; -0.014 | — |
| SECONDARY Change From Baseline Values for Erythrocyte Mean Corpuscular Hemoglobin in Part 1 |
0.16; 0.18; 0.19 | — |
| SECONDARY Change From Baseline Values for Erythrocyte Mean Corpuscular Volume in Part 1 |
0.09; 0.09; -0.01 | — |
| SECONDARY Change From Baseline Values for Erythrocytes in Part 1 |
0.191; 0.121; 0.221 | — |
| SECONDARY Change From Baseline Values for Hemocrit in Part 1 |
0.0164; 0.0099; 0.0188 | — |
| SECONDARY Change From Baseline Values for Hemoglobin in Part 1 |
6.1; 4.0; 7.2 | — |
| SECONDARY Change From Baseline Values for Hematology Parameters Including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 2 |
-0.004; -0.004; -0.008; 0.005; -0.006; 0.004 | — |
| SECONDARY Change From Baseline Values for Erythrocyte Mean Corpuscular Hemoglobin in Part 2 |
0.16; 0.07; -0.04 | — |
| SECONDARY Change From Baseline Values for Erythrocyte Mean Corpuscular Volume in Part 2 |
0.35; -0.01; 0.08 | — |
| SECONDARY Change From Baseline Values for Erythrocytes in Part 2 |
0.201; 0.224; 0.179 | — |
| SECONDARY Change From Baseline Values for Hemocrit in Part 2 |
0.0193; 0.0195; 0.0159 | — |
| SECONDARY Change From Baseline Values for Hemoglobin in Part 2 |
6.9; 6.8; 5.1 | — |
| SECONDARY Number of Participants With Abnormal Urinalysis Parameter in Part 1 |
17; 17; 18; 0; 0; 0 | — |
| SECONDARY Number of Participants With Urine Potential of Hydrogen (pH)-Part 1 |
14; 14; 15; 3; 3; 3 | — |
| SECONDARY Number of Participants With Abnormal Urinalysis Parameter in Part 2 |
18; 18; 18; 0; 0; 0 | — |
| SECONDARY Number of Participants With Urine Potential of Hydrogen (pH)-Part 2 |
11; 16; 13; 7; 2; 5 | — |
| SECONDARY Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Part 1 |
1; 0; 1; 0; 0; 0 | — |
| SECONDARY Number of Participants With Abnormal ECG Findings in Part 2 |
1; 1; 2; 0; 0; 0 | — |
| SECONDARY Absolute Values for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Part 1 |
117.5; 120.7; 118.9; 114.0; 115.2; 115.7 | — |
| SECONDARY Absolute Values for Pulse Rate in Part 1 |
59.5; 61.6; 59.7; 63.5; 66.6; 67.4 | — |
| SECONDARY Absolute Values for Temperature in Part 1 |
36.46; 36.44; 36.51; 36.41; 36.71; 36.66 | — |
| SECONDARY Absolute Values for SBP and DBP of Part 2 |
116.2; 118.9; 119.1; 116.0; 115.5; 113.2 | — |
| SECONDARY Absolute Values for Pulse Rate in Part 2 |
63.9; 62.6; 63.3; 67.7; 64.9; 66.5 | — |
| SECONDARY Absolute Values for Temperature in Part 2 |
36.31; 36.28; 36.39; 36.33; 36.35; 36.45 | — |
| SECONDARY Change From Baseline in SBP and DBP of Part 1 |
0.1; 3.9; 3.1; -3.4; -1.6; -0.2 | — |
| SECONDARY Change From Baseline in Pulse Rate of Part 1 |
-5.5; -4.4; -7.8; -1.5; 0.5; -0.1 | — |
| SECONDARY Change From Baseline in Temperature of Part 1 |
0.14; 0.02; 0.21; 0.09; 0.28; 0.36 | — |
| SECONDARY Change From Baseline in SBP and DBP of Part 2 |
-4.4; 0.9; -2.4; -4.6; -2.5; -8.3 | — |
| SECONDARY Change From Baseline in Pulse Rate in Part 2 |
-4.7; -5.7; -8.6; -0.9; -3.3; -5.4 | — |
| SECONDARY Change From Baseline in Temperature in Part 2 |
-0.01; 0.05; -0.02; 0.02; 0.12; 0.03 | — |
Eligibility Criteria
Inclusion Criteria
- Between 18 and 65 years of age, inclusive, at the time of signing the informed consent.
- Healthy subjects as determined by the investigator or medically qualified designee based on a medical evaluation, including medical history, physical examination, laboratory tests, and cardiac evaluation (history and ECG).
- Body weight >=50 kilogram (kg) for males and >=45 kg for females and body mass index (BMI) within the range 18.5 - 31.0 kilogram per square meter (kg/m^2) (inclusive).
- Male and female subjects where the male subjects must agree to use contraception during the TP and for at least 2 weeks plus an additional 90 days (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period. For the female subjects, female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin [hCG] test), not lactating, and at least 1 of the following conditions applies: Female with non-reproductive potential, defined as Premenopausal females with one of the following like documented tubal ligation, documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, documented hysterectomy, documented bilateral oophorectomy, the Postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT), and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment; Females with reproductive potential and agrees to follow one of the options for avoiding pregnancy in females of reproductive potential, from 30 days prior to the first dose of study medication and until 2 weeks after dosing with study medication and completion of the follow-up visit; the investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception; All female subjects participating in the study should be counselled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g., male condom) and on the risk of human immune virus (HIV) transmission to an uninfected partner.
- Subjects capable of giving signed informed consent.
- For participation in Part 1, documentation that the subject is negative for the human leukocyte antigen (HLA)-B*5701 allele.
Exclusion Criteria
- The medical conditions included where ALT and bilirubin >1.5 × upper limit of normal (ULN) (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin 100 beats per minute (bpm) and that for females be 100 bpm; the PR interval for both be 220 millisecond (msec); the QRS interval be 120 msec and the corrected Q-T interval (QTc) obtained using the Fridericia's formula (QTcF) be >450 msec ; ECG with evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization; any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular block [2nd degree or higher], Wolf-Parkinson-White syndrome); Sinus pauses > 3 seconds; any significant arrhythmia which, in the opinion of the principal investigator or ViiV/GlaxoSmithKline (GSK) medical monitor, will interfere with the safety of the individual subject; non-sustained or sustained ventricular tachycardia (3 consecutive ventricular ectopic beats).
- Subjects with use of prior or concomitant therapy who are unable to refrain from the use of prescription (e.g., dofetilide) or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's wort) within 7 days (or 14 days if the d
Data sourced from ClinicalTrials.gov (NCT03441984). 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.