A Drug Interaction Study Evaluating Plasma GSK2248761 and GSK1349572 Pharmacokinetics in Healthy Adult Subjects.
A Phase 1, Open Label, Single Sequence, Two-Way Drug Interaction Study Evaluating Plasma GSK2248761 and GSK1379572 Pharmacokinetics in Healthy Adult Subjects
Studienübersicht
Status
Status
Bedingungen
Bedingungen
Intervention / Behandlung
Intervention / Behandlung
Detaillierte Beschreibung
Studientyp
Studientyp
Phase
Phase
- Phase 1
Kontakte und Standorte
Studienorte
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New York
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Buffalo, New York, Vereinigte Staaten, 14202
- GSK Investigational Site
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Teilnahmekriterien
Zulassungskriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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).
- Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Subjects with a history of cholecystectomy should be excluded.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. In addition, if heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
Note: this does not include plasma donation.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- A positive test for HIV antibody.
- AST, ALT, alkaline phosphatase and bilirubin greater than or equal to 1.5xULN (isolated bilirubin >1.5x upper limit of normal (ULN) is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Pregnant females as determined by positive serum pregnancy test at screening or prior to dosing.
- Lactating females.
- The subject's systolic blood pressure is outside the range of 90-140 miligrams of mercury (mmHg), or diastolic blood pressure is outside the range of 45-90 mmHg or heart rate is outside the range of 50-100 beats per minute (bpm) for female subjects or 45-100 bpm for male subjects at Screening and predose Day 1.
- Cardiac conduction abnormalities denoted by any of the following on a single 12-lead ECG at screening or predose Day 1 (a single repeat is allowed for eligibility determination).
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Zuteilung: Zufällig
- Interventionsmodell: Crossover-Aufgabe
- Maskierung: Keine (Offenes Etikett)
Anzahl der Arme
Waffen und Interventionen
Teilnehmergruppe / ArmTeilnehmergruppe / Arm |
Intervention / BehandlungIntervention / Behandlung |
|---|---|
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Experimental: Treatment A
GSK1349572 50mg q24h x 7 days
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50mg once every 24 hours for 7 days
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Experimental: Treatment B
GSK2248761 200mg q24h x 7 days
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200 mg once every 24 hours for 7 days
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Experimental: Treatment C
GSK1349572 50mg q24h x 7 days + GSK2248761 200mg q24h x 7 days
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50mg once every 24 hours for 7 days
200 mg once every 24 hours for 7 days
|
Was misst die Studie?
Primäre Ergebnismessungen
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
|---|---|
|
Plasma GSK1349572 steady state area under the curve (AUC) 0-tau following 50 mg q24h administration with and without GSK2248761 200 mg q24h
Zeitfenster: 21 days
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21 days
|
|
Plasma GSK1349572 steady state maximum observed concentration (Cmax) following 50 mg q24h administration with and without GSK2248761 200 mg q24h
Zeitfenster: 21 days
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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
Zeitfenster: 21 days
|
21 days
|
|
Plasma GSK1349572 steady state predose concentration (C0) following 50 mg q24h administration with and without GSK2248761 200 mg q24h
Zeitfenster: 21 days
|
21 days
|
|
Plasma GSK1349572 steady state minimum concentration (Cmin) following 50 mg q24h administration with and without GSK2248761 200 mg q24h
Zeitfenster: 21 days
|
21 days
|
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Plasma GSK2248761 steady state steady state AUC 0-tau following 200 mg q24h administration with and without GSK1349572 50 mg q24h
Zeitfenster: 21 days
|
21 days
|
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Plasma GSK2248761 steady state Cmax following 200 mg q24h administration with and without GSK1349572 50 mg q24h
Zeitfenster: 21 days
|
21 days
|
|
Plasma GSK2248761 steady state Ctau following 200 mg q24h administration with and without GSK1349572 50 mg q24h
Zeitfenster: 21 days
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21 days
|
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Plasma GSK2248761 steady state Cmin following 200 mg q24h administration with and without GSK1349572 50 mg q24h
Zeitfenster: 21 days
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21 days
|
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Plasma GSK2248761 steady state C0 following 200 mg q24h administration with and without GSK1349572 50 mg q24h
Zeitfenster: 21 days
|
21 days
|
Sekundäre Ergebnismessungen
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
|---|---|
|
Safety and tolerability parameters, including the number of subjects with adverse events
Zeitfenster: approximately 42 days
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approximately 42 days
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Safety and tolerability parameters, including the number of subjects receiving concurrent medications
Zeitfenster: approximately 42 days
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approximately 42 days
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Safety and tolerability parameters, including change from baseline for clinical laboratory safety assessments
Zeitfenster: approximately 42 days
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approximately 42 days
|
|
Safety and tolerability parameters, including change from baseline for electrocardiogram (ECG) assessments
Zeitfenster: approximately 42 days
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approximately 42 days
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Safety and tolerability parameters, including change from baseline for vital sign (blood pressure and heart rate) assessments
Zeitfenster: approximately 42 days
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approximately 42 days
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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)
Zeitfenster: approximately 28 days
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approximately 28 days
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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)
Zeitfenster: 21 days
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21 days
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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)
Zeitfenster: 21 days
|
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)
Zeitfenster: 21 days
|
21 days
|
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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)
Zeitfenster: 21 days
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21 days
|
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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).
Zeitfenster: 21 days
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21 days
|
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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).
Zeitfenster: 21 days
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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).
Zeitfenster: 21 days
|
21 days
|
|
GSK1349572 and GSK2248761 Ctau values on Days 4-7 for each Period
Zeitfenster: 21 days
|
21 days
|
Mitarbeiter und Ermittler
Sponsor
Sponsor
Mitarbeiter
Mitarbeiter
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Studienbeginn
Primärer Abschluss (Tatsächlich)
Primärer Abschluss
Studienabschluss (Voraussichtlich)
Studienabschluss
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Zuerst gepostet
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Schätzen)
Letztes Update gepostet
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- RNA-Virusinfektionen
- Viruserkrankungen
- Infektionen
- Durch Blut übertragene Infektionen
- Übertragbare Krankheiten
- Sexuell übertragbare Krankheiten, viral
- Sexuell übertragbare Krankheiten
- Lentivirus-Infektionen
- Retroviridae-Infektionen
- Immunologische Mangelsyndrome
- Erkrankungen des Immunsystems
- Langsame Viruserkrankungen
- HIV-Infektionen
- Erworbenes Immunschwächesyndrom
- Molekulare Mechanismen der pharmakologischen Wirkung
- Antiinfektiva
- Antivirale Mittel
- Enzym-Inhibitoren
- Anti-HIV-Agenten
- Antiretrovirale Mittel
- HIV-Integrase-Inhibitoren
- Integrase-Inhibitoren
- Dolutegravir
Andere Studien-ID-Nummern
Andere Studien-ID-Nummern
- 114122
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