Infection, Human Immunodeficiency Virus
Conditions
Keywords
healthy volunteers, drug interaction, carbamazepine, Dolutegravir, pharmacokinetics
Brief summary
This study will be a phase I, open label, three period, fixed sequence crossover study to evaluate the effect of Carbamazepine (CBZ) on the steady-state pharmacokinetics of Dolutegravir (DTG) and on the safety and tolerability of DTG. Subjects will have a screening visit within 30 days prior to the first dose of study drug, three treatment periods, and a follow-up visit 7-14 days after the last dose of study drug. There is no washout between treatment periods.
Interventions
Sponsors
GlaxoSmithKline
ViiV Healthcare
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy as determined by a responsible and experienced physician, based on a medical evaluation including \[medical history, physical examination, laboratory tests and cardiac monitoring\]. 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 agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Male/females aged between 18 and 65 years of age inclusive, at the time of signing the informed consent. * A female subject is eligible to participate if she is of: non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, bilateral oophorectomy or hysterectomy \[for this definition, documented refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records\]; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \>40 milli international units per milliliter (MIU/mL) and estradiol \<40 picograms (pg)/mL (\<147 picomole per liter (pmol/L) is confirmatory\]; Child-bearing potential with negative pregnancy test as determined by \[serum or urine\] human chorionic gonadotropin (hCG) test at screening or prior to dosing AND Agrees to use one of the contraception methods for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 5 days post-last dose. OR has only same-sex partners, when this is her preferred and usual lifestyle. * Body weight \>=50 kilograms (Kg) for males and \>=45 Kg for females and body mass index (BMI) within the range 18.5 - 31.0 Kg/m\^2 (square meters) (inclusive). * Alanine aminotransferase, alkaline phosphatase and bilirubin \<= 1.5x Upper Limit of Normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). A single repeat is allowed for eligibility determination. * Based on single corrected QT interval (QTc) value: QT duration corrected for heart rate by Bazett's formula (QTcB) \<450 millisecond (msec); or QTc \<480 msec in subjects with Bundle Branch Block. * A negative HLA-B\*1502 allele screening assessment for subjects of Asian ethnicity only. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Steady state plasma DTG pharmacokinetics (PK) parameters | Day 5 and Day 26 | PK parameters will include: Steady state plasma DTG concentration at the end of the dosing interval (Ctau), maximum concentration (Cmax), area under the time-concentration curve over the dosing interval \[AUC(0-tau)\], apparent clearance following oral dosing (CL/F), terminal phase half life (t1/2), concentration at time zero (C0) and minimum concentration (Cmin) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in 12-lead electrocardiogram (ECG) | Up to 40 days | Single 12-lead ECGs will be obtained at each timepoint |
| Change from baseline in vital signs | Up to 40 days | Vital signs will include systolic and diastolic blood pressure and pulse rate |
| Number of subjects with adverse events (AEs) | Up to 40 days | AEs will be assessed throughout the study |
| Toxicity grading of clinical laboratory tests | Up to 40 days | Laboratory assessments will include haematology, clinical chemistry and urinalysis parameters |
Countries
United States
Outcome results
None listed