A Phase 1, Open Label, Single Sequence, Two-Way Drug Interaction Study Evaluating Plasma GSK2248761 and GSK1379572 Pharmacokinetics in Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- GSK2248761
- Conditions
- Infection, Human Immunodeficiency Virus I
- Sponsor
- ViiV Healthcare
- Locations
- 1
- Primary Endpoint
- Plasma GSK1349572 steady state area under the curve (AUC) 0-tau following 50 mg q24h administration with and without GSK2248761 200 mg q24h
- Status
- Withdrawn
- Last Updated
- 11 years ago
Overview
Brief Summary
This is a single-center, open-label, three-period, fixed-sequence cross over study in healthy adult subjects. A total of approximately 16 healthy subjects will be enrolled to provide data from 12 evaluable subjects. 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 will be a washout period between Period 1 and Period 2 but no washout between Period 2 and Period 3. Day 1 of Period 3 will be the day after Day 5 of Period 2.
Detailed Description
ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests, and electrocardiograms (ECGs).
- •A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- •Male or female between 18 and 55 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 (i.e., physiologically incapable of becoming pregnant) including any female who: Is pre-menopausal with a documented bilateral tubal ligation, bilateral oophorectomy (removal of the ovaries) or hysterectomy, or is post-menopausal defined as 12 months of spontaneous amenorrhea. A follicle stimulating hormone (FSH) level will be performed to confirm a post-menopausal status. For this study, FSH levels \> 40 MlU/ml is confirmatory.
- •Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until the follow-up visit.
- •Body weight less than or equal to 50 kg for men and less than or equal to 45 kg for women and body mass index (BMI) within the range 18.5-31.0 kg/m2 (inclusive).
- •Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
Exclusion Criteria
- •As a result of the medical interview, physical examination, or screening investigations, the Investigator considers the subject unfit for the study.
- •The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
- •Unwilling to refrain from the use of illicit drugs and adhere to other protocol-stated restrictions while participating in the study.
- •History of regular alcohol consumption within 6 months of the study.
- •Unwilling to abstain from alcohol for 48 hours prior to the start of dosing until collection of the final pharmacokinetic sample during each treatment period.
- •History or regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
- •History/evidence of symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PCTA) or any clinically significant cardiac disease.
- •History/evidence of clinically significant pulmonary disease.
- •History/evidence of pancreatitis.
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Arms & Interventions
Treatment B
GSK2248761 200mg q24h x 7 days
Intervention: GSK2248761
Treatment A
GSK1349572 50mg q24h x 7 days
Intervention: GSK1349572
Treatment C
GSK1349572 50mg q24h x 7 days + GSK2248761 200mg q24h x 7 days
Intervention: GSK1349572
Treatment C
GSK1349572 50mg q24h x 7 days + GSK2248761 200mg q24h x 7 days
Intervention: GSK2248761
Outcomes
Primary Outcomes
Plasma GSK1349572 steady state area under the curve (AUC) 0-tau following 50 mg q24h administration with and without GSK2248761 200 mg q24h
Time Frame: 21 days
Plasma GSK2248761 steady state Cmax following 200 mg q24h administration with and without GSK1349572 50 mg q24h
Time Frame: 21 days
Plasma GSK2248761 steady state C0 following 200 mg q24h administration with and without GSK1349572 50 mg q24h
Time Frame: 21 days
Plasma GSK1349572 steady state Pre-dose trough concentration at the end of the dosing interval (Ctau) following 50 mg q24h administration with and without GSK2248761 200 mg q24h
Time Frame: 21 days
Plasma GSK2248761 steady state steady state AUC 0-tau following 200 mg q24h administration with and without GSK1349572 50 mg q24h
Time Frame: 21 days
Plasma GSK2248761 steady state Cmin following 200 mg q24h administration with and without GSK1349572 50 mg q24h
Time Frame: 21 days
Plasma GSK1349572 steady state maximum observed concentration (Cmax) following 50 mg q24h administration with and without GSK2248761 200 mg q24h
Time Frame: 21 days
Plasma GSK1349572 steady state predose concentration (C0) following 50 mg q24h administration with and without GSK2248761 200 mg q24h
Time Frame: 21 days
Plasma GSK1349572 steady state minimum concentration (Cmin) following 50 mg q24h administration with and without GSK2248761 200 mg q24h
Time Frame: 21 days
Plasma GSK2248761 steady state Ctau following 200 mg q24h administration with and without GSK1349572 50 mg q24h
Time Frame: 21 days
Secondary Outcomes
- GSK2248761 PK parameters tmax following administration of GSK2248761 200 mg q24h with and without co-administration of GSK1349572 50 mg q24h (Day 7 in Period 2 and Day 7 in Period 3)(21 days)
- GSK2248761 PK parameters CL/F following administration of GSK2248761 200 mg q24h with and without co-administration of GSK1349572 50 mg q24h (Day 7 in Period 2 and Day 7 in Period 3).(21 days)
- Safety and tolerability parameters, including change from baseline for vital sign (blood pressure and heart rate) assessments(approximately 42 days)
- GSK1349572 PK parameters including apparent clearance following oral dosing (CL/F) of GSK1349572 50 mg q24h with and without co-administration of GSK2248761 200 mg q24h (Day 7 in Period 1, Period 3)(21 days)
- Safety and tolerability parameters, including change from baseline for clinical laboratory safety assessments(approximately 42 days)
- Safety and tolerability parameters, including the number of subjects with adverse events(approximately 42 days)
- Safety and tolerability parameters, including the number of subjects receiving concurrent medications(approximately 42 days)
- Safety and tolerability parameters, including change from baseline for electrocardiogram (ECG) assessments(approximately 42 days)
- GSK1349572 PK parameters including time of occurrence of maximum concentration (tmax) following administration of GSK1349572 50 mg q24h with and without co-administration of GSK2248761 200 mg q24h (Day 7 in Period 1, Period 3)(approximately 28 days)
- GSK1349572 PK parameters including time of occurrence of minimum concentration (Tmin) following administration of GSK1349572 50 mg q24h with and without co-administration of GSK2248761 200 mg q24h (Day 7 in Period 1, Period 3)(21 days)
- GSK1349572 PK parameters including terminal half life (t½) following administration of GSK1349572 50 mg q24h with and without co-administration of GSK2248761 200 mg q24h (Day 7 in Period 1, Period 3)(21 days)
- GSK2248761 PK parameters tmin following administration of GSK2248761 200 mg q24h with and without co-administration of GSK1349572 50 mg q24h (Day 7 in Period 2 and Day 7 in Period 3).(21 days)
- GSK2248761 PK parameters t½ following administration of GSK2248761 200 mg q24h with and without co-administration of GSK1349572 50 mg q24h (Day 7 in Period 2 and Day 7 in Period 3).(21 days)
- GSK1349572 and GSK2248761 Ctau values on Days 4-7 for each Period(21 days)