- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT02000765
A Study to Investigate the Recovery, Excretion and Pharmacokinetics of [14C]-GSK2140944 Administered as a Single Intravenous and Single Oral Dose to Healthy Adult Male Subjects
10. Juli 2017 aktualisiert von: GlaxoSmithKline
An Open-Label, Non-Randomized, Two-Period, Cross-Over, Mass Balance Study to Investigate the Recovery, Excretion and Pharmacokinetics of 14C-GSK2140944 Administered as a Single Intravenous and Single Oral Dose to Healthy Adult Male Subjects (BTZ115774)
This is an open-label, non-randomized, two-period, cross-over, mass balance study that will evaluate the recovery, excretion, and pharmacokinetics of a single intravenous (IV) dose of [14C]-GSK2140944 (Period 1) and a single oral dose of [14C]-GSK2140944 ( Period 2) in 6 healthy male subjects.
The results from this study will aid in the design of future clinical pharmacology studies such as the thorough corrected QT interval study, special population studies (renal, hepatic, critically ill patients), potential drug interaction studies, and will help to establish safe and efficacious intravenous and oral dosing regimens.
Studienübersicht
Status
Abgeschlossen
Bedingungen
Intervention / Behandlung
Studientyp
Interventionell
Einschreibung (Tatsächlich)
6
Phase
- Phase 1
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
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London, Vereinigtes Königreich, NW10 7NS
- GSK Investigational Site
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Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
30 Jahre bis 55 Jahre (Erwachsene)
Akzeptiert gesunde Freiwillige
Ja
Studienberechtigte Geschlechter
Männlich
Beschreibung
Inclusion Criteria:
- A subject will be eligible for inclusion in this study only if all of the following criteria apply:
- Male aged between 30 and 55 years of age inclusive, at the time of signing the informed consent.
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests and cardiac monitoring.
- A subject with a clinical abnormality or laboratory parameter outside the reference range for the population being studied may be included only if the Investigator feels and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Body weight >=50 kilogram and Body Mass Index within the range 19- 31 kilogram per square meter (inclusive).
- Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and bilirubin <=1.5xupper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- A history of regular bowel movements (averaging one or more bowel movements per day).
- Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in Protocol. This criterion must be followed from the time of the first dose of study medication until four months after the last dose.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Exclusion Criteria:
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >21 units for males. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 ml) of beer, 1 glass (125 milliliter [mL]) of wine or 1 (25 mL) measure of spirits.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- 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.
- 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 must be excluded.
- History of sensitivity to quinolones including photosensitivity and tendon rupture.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening or positive test for Human Immunodeficiency Virus (HIV) antibody.
- A screening or Day -1 urinalysis positive for protein or glucose (greater than "1+" findings of protein or glucose).
- A serum creatinine value between screening and Day -1 visit that is increased by more than 0.2 milligrams per decilitre (or 15.25 micromole per liter) changes.
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- A positive pre-study drug/alcohol screen.
- Exclusion criteria for screening and baseline ECG (a single repeat is allowed for eligibility determination): Heart rate <40 and >100 beats per minute; PR Interval <120 and >220 milliseconds (msec); QRS duration <70 and >100 msec; QT duration corrected for heart rate by Bazett's formula (QTcB) or QT duration corrected for heart rate by Fridericia's formula (QTcF) interval >450 msec; Evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization); Any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular block [second degree or higher], Wolf Parkinson White [WPW] syndrome), sinus pauses> 3 seconds, non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats) or any significant arrhythmia which, in the opinion of the principal investigator and GSK medical monitor, will interfere with the safety of the individual subject.
- Where participation in the study would result in donation of blood or blood products in excess of 500 millilitre (mL) within a 56 day period.
- 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).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
Subjects who have received a total body radiation dose of greater than 5.0 millisievert (upper limit of World Health Organization category II) or exposure to significant radiation (e.g. serial x-ray or CT scans, barium meal etc) in the 12 months prior to this study.
- Any condition that could interfere with the accurate assessment and recovery of radioactivity [14C].
- Participation in a clinical trial involving administration of 14C-labelled compound(s) within the last 12 months.
- Unwillingness to commit to avoid excessive exposure to sunlight (or exposure whilst on a tanning bed) which would cause a sunburn reaction from first dose up to and including discharge.
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Nicht randomisiert
- Interventionsmodell: Crossover-Aufgabe
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
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Experimental: GSK2140944 for Injection and Capsule
Each subject will receive a single 1000 milligram (mg) IV dose of GSK2140944 containing [14C]-GSK2140944 of approximately 22.5 microcurie [μCi] (approximately 0.8 megabecquerel [MBq]) of radioactivity given as a 2 hour infusion on Day 1 of treatment period 1 and 2000 mg oral dose of GSK2140944 containing [14C]-GSK2140944 of approximately 45 μCi (approximately 1.7 MBq) of radioactivity on Day 1 of treatment period 2. Each treatment period will be followed with washout of atleast 8 Days.
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GSK2140944 (1 gram) for Injection will be supplied as powder for injection containing [14C] GSK2140944.
Non sterile powder is to be dissolved aseptically in sterile water for injection to a concentration of 4 mg/mL free base equivalent.
IV solution is prepared by sterile filtration.
250 mL of IV solution, equivalent to 1000 mg GSK2140944, is then administered intravenously.
GSK2140944 Capsule (2 gram) will be supplied as powder in capsule containing [14C] GSK2140944.
Powder is to be filled in empty capsule to achieve 200-400 mg strength per capsules as free base equivalent.
Sufficient capsules are administered to provide the required total dose of 2 gram as free base.
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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GSK2140944 PK parameters following single IV or oral doses of [14C]-GSK2140944
Zeitfenster: Pre-dose and post dose(0 minute [min], 15 min, 30 min, 60 min, 120 min, 2.5 hour[hr], 3 hr, 4 hr, 6 hr, 6.5 hr, 8 hr, 12 hr, 16 hr, 24 hr, 48 hr, 72hr, 96 hr, 120hr, 144 hr, 168 hr, 48 hr, 72 hr, 96 hr, 120 hr, 144 hr and 168 hr) of each treatment period
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From the plasma concentration-time and blood/plasma radioactivity concentration-time data, the following pharmacokinetic parameters will be determined, as data permit: maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve [AUC(0-t) and AUC(0-∞)], and apparent terminal phase half-life (t1/2).
Systemic clearance (CL) and volume of distribution (Vdss) of GSK2140944 may be calculated for IV regimen only.
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Pre-dose and post dose(0 minute [min], 15 min, 30 min, 60 min, 120 min, 2.5 hour[hr], 3 hr, 4 hr, 6 hr, 6.5 hr, 8 hr, 12 hr, 16 hr, 24 hr, 48 hr, 72hr, 96 hr, 120hr, 144 hr, 168 hr, 48 hr, 72 hr, 96 hr, 120 hr, 144 hr and 168 hr) of each treatment period
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Total recovery of radioactivity in urine and feces following separate single IV and oral doses of [14C]-GSK2140944
Zeitfenster: Pre-dose and post dose(0-6 hr, 6 12 hr, 12 24 hr, 48 hr, 72 hr, 96 hr, 120 hr, 144 hr, 168 hr, 48 hr, 72 hr, 96 hr, 120 hr, 144 hr and 168 hr) of each treatment period
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Total recovery of radioactivity in urine and feces is defined as a percentage of total radioactive dose in each interval and cumulatively.
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Pre-dose and post dose(0-6 hr, 6 12 hr, 12 24 hr, 48 hr, 72 hr, 96 hr, 120 hr, 144 hr, 168 hr, 48 hr, 72 hr, 96 hr, 120 hr, 144 hr and 168 hr) of each treatment period
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Number of subjects with adverse events (AE)
Zeitfenster: Up to 7 weeks
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Up to 7 weeks
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Safety and tolerability of GSK2140944 after single IV and oral doses as assessed by concomitant medications review
Zeitfenster: Up to 7 weeks
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Up to 7 weeks
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Safety and tolerability of GSK2140944 after single IV and oral doses as assessed by clinical laboratory tests
Zeitfenster: Day 1 and Day 8 of each treatment period
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clinical laboratory tests includes hematology, clinical chemistry, urinalysis
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Day 1 and Day 8 of each treatment period
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Safety and tolerability of GSK2140944 after single IV and oral doses as assessed by electrocardiogram (ECG)
Zeitfenster: Day 1 (Pre dose and 1 hr, 2 hr, 4 hr and 8 hr post dose)and Day 8 of each treatment period
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Single 12-lead ECGs will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT interval (QTc) intervals.
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Day 1 (Pre dose and 1 hr, 2 hr, 4 hr and 8 hr post dose)and Day 8 of each treatment period
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Safety and tolerability of GSK2140944 after single IV and oral doses as assessed by vital signs
Zeitfenster: Day 1 (Pre dose and 1 hr, 2 hr, 4 hr and 8 hr post dose)and Day 8 of each treatment period
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Vital sign measurements to be measurement include systolic and diastolic blood pressure, pulse rate and temperature.
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Day 1 (Pre dose and 1 hr, 2 hr, 4 hr and 8 hr post dose)and Day 8 of each treatment period
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Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Sponsor
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn (Tatsächlich)
8. November 2013
Primärer Abschluss (Tatsächlich)
30. November 2013
Studienabschluss (Tatsächlich)
30. November 2013
Studienanmeldedaten
Zuerst eingereicht
7. November 2013
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
27. November 2013
Zuerst gepostet (Schätzen)
4. Dezember 2013
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
13. Juli 2017
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
10. Juli 2017
Zuletzt verifiziert
1. Juli 2017
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- 115774
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
JA
Beschreibung des IPD-Plans
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Studiendaten/Dokumente
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Kommentiertes Fallberichtsformular
Informationskennung: 115774Informationskommentare: For additional information about this study please refer to the GSK Clinical Study Register
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Klinischer Studienbericht
Informationskennung: 115774Informationskommentare: For additional information about this study please refer to the GSK Clinical Study Register
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Einzelner Teilnehmerdatensatz
Informationskennung: 115774Informationskommentare: For additional information about this study please refer to the GSK Clinical Study Register
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Statistischer Analyseplan
Informationskennung: 115774Informationskommentare: For additional information about this study please refer to the GSK Clinical Study Register
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Einwilligungserklärung
Informationskennung: 115774Informationskommentare: For additional information about this study please refer to the GSK Clinical Study Register
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Studienprotokoll
Informationskennung: 115774Informationskommentare: For additional information about this study please refer to the GSK Clinical Study Register
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Datensatzspezifikation
Informationskennung: 115774Informationskommentare: For additional information about this study please refer to the GSK Clinical Study Register
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .