Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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 TRIUMEQâ„¢ ([abacavir, ABC]/[dolutegravir, DTG]/[lamivudine, 3TC]) when dispersed and consumed under four different dosing conditions in comparison to an oral dose of TIVICAYâ„¢ (DTG) + EPZICOMâ„¢ (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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SEQUENCE ABCDE | Experimental | Participants will receive treatment A in period 1, treatment B in period 2, treatment C in period 3, treatment D in period 4 and treatment E in period 5 (one treatment per period). Where A=EPZICOM (ABC 600 milligrams (mg)/3TC 300 mg) plus four TIVICAY (DTG 10 mg) tablets with zero mineral content (ZMC) water. B=Four TRIUMEQ (ABC 150mg/DTG 10 mg/3TC 75 mg) tablets dispersed in 40 milliliter (mL) stock solution 1 and consumed immediately. C=Four TRIUMEQ tablets dispersed in 40 mL stock solution 1, held for 30 minutes(mins), re-dispersed, and then consumed. D=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2 and consumed immediately. E=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2, held for 30 mins, re-dispersed, and then consumed. |
|
| SEQUENCE BCDEA | Experimental | Participants will receive treatment B in period 1, treatment C in period 2, treatment D in period 3, treatment E in period 4 and treatment A in period 5 (one treatment per period). Where A= EPZICOM (ABC 600 milligrams (mg)/3TC 300 mg) plus four TIVICAY (DTG 10 mg) tablets with ZMC water. B=Four TRIUMEQ (ABC 150mg/DTG 10 mg/3TC 75 mg) tablets dispersed in 40 mL stock solution 1 and consumed immediately. C=Four TRIUMEQ tablets dispersed in 40 mL stock solution 1, held for 30 mins, re-dispersed, and then consumed. D=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2 and consumed immediately. E=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2, held for 30 mins, re-dispersed, and then consumed. |
|
| SEQUENCE CDEAB | Experimental | Participants will receive treatment C in period 1, treatment D in period 2, treatment E in period 3, treatment A in period 4 and treatment B in period 5 (one treatment per period). Where A=EPZICOM (ABC 600 milligrams (mg)/3TC 300 mg) plus four TIVICAY (DTG 10 mg) tablets with ZMC water. B=Four TRIUMEQ (ABC 150mg/DTG 10 mg/3TC 75 mg) tablets dispersed in 40 mL stock solution 1 and consumed immediately. C=Four TRIUMEQ tablets dispersed in 40 mL stock solution 1, held for 30 mins, re-dispersed, and then consumed. D=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2 and consumed immediately. E=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2, held for 30 mins, re-dispersed, and then consumed. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DTG/ABC/3TC FDC DISPERSIBLE TABLET | Drug | DTG/ABC/3TC FDC dispersible tablet |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area under the plasma concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinity]) of DTG, ABC, and 3TC | Blood samples will be collected at pre-dose and at specific post-dose time points for calculating AUC [0- infinity] | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose |
| Maximum observed plasma concentration (Cmax) of DTG, ABC, and 3TC | Blood samples will be collected at pre-dose and at specific post dose time points for calculating Cmax | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose |
| Measure | Description | Time Frame |
|---|---|---|
| Area under the plasma concentration-time curve from time zero (pre-dose) to 24 hours (h) AUC(0-24) of DTG, ABC, and 3TC | AUC(0-24) is defined as the area under the concentration-time curve from time zero (pre-dose) to 24 h post-dose. | 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. |
Not provided
Inclusion Criteria
Exclusion Criteria
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | ViiV Healthcare | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Overland Park | Kansas | 66211 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30239425 | Derived | Singh RP, Shaik JSB, Skoura N, Joshi S, Shreeves T, Casillas L, Buchanan AM. Effects of Low- and High-Mineral Content Water on the Relative Bioavailability of a Coformulated Abacavir/Dolutegravir/Lamivudine Dispersible Tablet in Healthy Adults. J Acquir Immune Defic Syndr. 2018 Dec 15;79(5):631-638. doi: 10.1097/QAI.0000000000001859. |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D007239 | Infections |
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D015229 | Sexually Transmitted Diseases, Viral |
Not provided
Not provided
| ID | Term |
|---|---|
| C492871 | abacavir, lamivudine drug combination |
| C562325 | dolutegravir |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| SEQUENCE DEABC | Experimental | Participants will receive treatment D in period 1, treatment E in period 2, treatment A in period 3, treatment B in period 4 and treatment C in period 5 (one treatment per period). Where A=EPZICOM (ABC 600 milligrams (mg)/3TC 300 mg) plus four TIVICAY (DTG 10 mg) tablets with ZMC water. B=Four TRIUMEQ (ABC 150mg/DTG 10 mg/3TC 75 mg) tablets dispersed in 40 mL stock solution 1 and consumed immediately. C=Four TRIUMEQ tablets dispersed in 40 mL stock solution 1, held for 30 mins, re-dispersed, and then consumed. D=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2 and consumed immediately. E=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2, held for 30 mins, re-dispersed, and then consumed. |
|
| SEQUENCE EABCD | Experimental | Participants will receive treatment E in period 1, treatment A in period 2, treatment B in period 3, treatment C in period 4 and treatment D in period 5 (one treatment per period). Where A=EPZICOM (ABC 600 milligrams (mg)/3TC 300 mg) plus four TIVICAY (DTG 10 mg) tablets with ZMC water. B=Four TRIUMEQ (ABC 150mg/DTG 10 mg/3TC 75 mg) tablets dispersed in 40 mL stock solution 1 and consumed immediately. C=Four TRIUMEQ tablets dispersed in 40 mL stock solution 1, held for 30 mins, re-dispersed, and then consumed. D=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2 and consumed immediately. E=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2, held for 30 mins, re-dispersed, and then consumed. |
|
| EPZICOM (ABC/3TC) | Drug | EPZICOM will be available as orange, film coated, modified capsule shaped tablets, debossed with "GS FC2" on one side. |
|
| TIVICAY (DTG) | Drug | TIVICAY will be available as white, round, biconvex tablets |
|
| 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 |
Blood samples will be collected at pre-dose and at specific post dose time points for calculating AUC [0-t] |
| 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. |
| Time to maximum plasma concentration (Tmax) of DTG, ABC, and 3TC | Blood samples will be collected at pre-dose and at specific post-dose time points for calculating Tmax | 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. |
| Apparent clearance following oral dosing (CL/F) of DTG, ABC, and 3TC | Blood samples will be collected at pre-dose and at specific post-dose time points for calculating CL/F | 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. |
| Concentration at 24 h after dose administration (C24) of DTG, ABC, and 3TC | Blood samples will be collected at pre-dose and at specific post-dose time points for calculating C24 | 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. |
| Terminal phase half-time (t1/2) of DTG, ABC, and 3TC | Blood samples will be collected at pre-dose and at specific post-dose time points for calculating t1/2 | 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 (Tlag) of DTG | Absorption lag time is defined as the time taken for a drug to appear in the systemic circulation following administration | 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. |
| Number of subjects with adverse event (AE) and serious adverse event (SAE). | 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. | Approximately 11 weeks |
| Blood pressure assessment as a safety measure | 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 | Approximately 11 weeks |
| Measurement of pulse rate as a safety measure | 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 | Approximately 11 weeks |
| Body temperature assessment as a safety measure | 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 | Approximately 11 weeks |
| Electrocardiogram (ECG) assessment as a measure of safety | 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 | Approximately 11 weeks |
| Number of subjects having abnormal clinical laboratory parameters as a measure of safety | 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 | Approximately 11 weeks |
| Number of subjects having abnormal hematology laboratory parameters as a measure of safety | 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 | Approximately 11 weeks |
| Number of subjects having abnormal urinalysis as a measure of safety | 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 | Approximately 11 weeks |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |