Infection, Human Immunodeficiency Virus
Conditions
Keywords
dolutegravir, abacavir, relative bioavailability, palatability, GSK2619619, palatability questionnaire, lamivudine, pediatric, calcium, dispersible tablet
Brief summary
This is an open-label, randomized, crossover study in healthy adult subjects with 5 treatment groups over 5 dosing periods. This study will evaluate pharmacokinetic parameters and relative bioavailability of a dispersible, fixed-dose combination (FDC) tablet of TRIUMEQ™ (\[abacavir, ABC\]/\[dolutegravir, DTG\]/\[lamivudine, 3TC\]) when dispersed and consumed under four different dosing conditions in comparison to an oral dose of TIVICAY™ (DTG) + EPZICOM™ (ABC/3TC) non-dispersible tablets administered in the fasted state. Approximately 20 subjects will be randomized, each to one of 5 treatment groups. The total duration of participation of a subject in this study will be approximately 10-11 weeks. It will include a screening visit within 30 days prior to the first dose of study drug, five treatment periods each with a single dose of study drug per treatment period and a follow up visit within 7 10 days after the last dose. There will also be a washout of at least 7 days between doses in each treatment period. TRIUMEQ, EPZICOM, and TIVICAY are trademarks of the GlaxoSmithKline group of companies.
Interventions
DRUGDTG/ABC/3TC FDC DISPERSIBLE TABLET
DTG/ABC/3TC FDC dispersible tablet
DRUGEPZICOM (ABC/3TC)
EPZICOM will be available as orange, film coated, modified capsule shaped tablets, debossed with GS FC2 on one side.
DRUGTIVICAY (DTG)
TIVICAY will be available as white, round, biconvex tablets
Sponsors
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female aged between 18 and 65 years of age inclusive, at the time of signing the informed consent. * Healthy 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). A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included only if the investigator agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body weight \>=50 kilogram (kg) for males and \>=45 kg for females and body mass index (BMI) within the range 18.5-31.0 kg/m\^2 (inclusive). * Male or female * Females of non-reproductive potential defined as pre-menopausal females with documented tubal ligation, documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, hysterectomy, documented bilateral oophorectomy, postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone \[FSH\] 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. * Female of reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) 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. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. * Documentation that the subject is negative for the human leukocyte antigen (HLA)-B\*5701 allele.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the plasma concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinity]) of DTG, ABC, and 3TC | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose | Blood samples will be collected at pre-dose and at specific post-dose time points for calculating AUC \[0- infinity\] |
| Maximum observed plasma concentration (Cmax) of DTG, ABC, and 3TC | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose | Blood samples will be collected at pre-dose and at specific post dose time points for calculating Cmax |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the plasma concentration-time curve from time zero (pre-dose) to 24 hours (h) AUC(0-24) of DTG, ABC, and 3TC | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24h post dose in each of the 5 treatment periods. | AUC(0-24) is defined as the area under the concentration-time curve from time zero (pre-dose) to 24 h post-dose. |
| Area under the plasma concentration-time curve from time zero (pre-dose) to time of last measurable concentration (AUC[0 t]) of DTG, ABC, and 3TC | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose in each of the 5 treatment periods. | Blood samples will be collected at pre-dose and at specific post dose time points for calculating AUC \[0-t\] |
| Time to maximum plasma concentration (Tmax) of DTG, ABC, and 3TC | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose in each of the 5 treatment periods. | Blood samples will be collected at pre-dose and at specific post-dose time points for calculating Tmax |
| Apparent clearance following oral dosing (CL/F) of DTG, ABC, and 3TC | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose in each of the 5 treatment periods. | Blood samples will be collected at pre-dose and at specific post-dose time points for calculating CL/F |
| Concentration at 24 h after dose administration (C24) of DTG, ABC, and 3TC | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24h post dose in each of the 5 treatment periods. | Blood samples will be collected at pre-dose and at specific post-dose time points for calculating C24 |
| Terminal phase half-time (t1/2) of DTG, ABC, and 3TC | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose in each of the 5 treatment periods. | Blood samples will be collected at pre-dose and at specific post-dose time points for calculating t1/2 |
| Absorption lag time (Tlag) of DTG | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose in each of the 5 treatment periods. | Absorption lag time is defined as the time taken for a drug to appear in the systemic circulation following administration |
| Number of subjects with adverse event (AE) and serious adverse event (SAE). | Approximately 11 weeks | AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE. |
| Blood pressure assessment as a safety measure | Approximately 11 weeks | Systolic and diastolic blood pressure will be measured in supine or semi-supine position after 5 minutes rest at Day -1, pre-dose, 4h, 24h, 48 h, 72h post-dose, and at follow up |
| Measurement of pulse rate as a safety measure | Approximately 11 weeks | Heart rate will be measured at supine or semi-supine position after 5 minutes rest at Day -1, pre-dose, 4h, 24h, 48 h, 72h post-dose, and at follow up |
| Body temperature assessment as a safety measure | Approximately 11 weeks | Temperature will be recorded at supine or semi-supine position after 5 minutes rest at Day -1, pre-dose, 4h, 24h, 48 h, 72h post-dose, and at follow up |
| Electrocardiogram (ECG) assessment as a measure of safety | Approximately 11 weeks | Single 12-lead ECGs will be obtained in a supine or semi-supine position having rested in this position for at least 10 minutes beforehand at Day -1 of each of 5 treatment periods |
| Number of subjects having abnormal clinical laboratory parameters as a measure of safety | Approximately 11 weeks | Blood samples will be collected (at Day -1, and 24 h post-dose and at follow-up if needed) to analyze blood urea nitrogen, creatinine, glucose, creatine phosphokinase (CPK), sodium, potassium, calcium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, direct bilirubin, total protein, albumin |
| Number of subjects having abnormal hematology laboratory parameters as a measure of safety | Approximately 11 weeks | Blood samples will be collected (at Day -1 and 24h post-dose and at follow-up if needed) to analyze platelet count, Red Blood Cells (RBC) count, hemoglobin, hematocrit, mean corpuscular volume ( MCV), mean corpuscular hemoglobin (MCH) White Blood Cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, and basophils |
| Number of subjects having abnormal urinalysis as a measure of safety | Approximately 11 weeks | Urine samples will be collected (at Day -1, and 24 h post-dose and at follow-up if needed) to analyze specific gravity, pH, glucose, protein, blood and ketones by dipstick, and for microscopic examination |
Countries
United States
Outcome results
None listed