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Trial record 2 of 9 for:    retosiban

A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Retosiban (GSK221149) When Dosed With Efavirenz (EFZ)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01867996
Recruitment Status : Completed
First Posted : June 4, 2013
Last Update Posted : May 11, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE May 30, 2013
First Posted Date  ICMJE June 4, 2013
Last Update Posted Date May 11, 2017
Actual Study Start Date  ICMJE June 11, 2013
Actual Primary Completion Date September 26, 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 30, 2013)
Plasma GSK221149 (parent) and GSK2847065 (metabolite) PK parameters of AUC, Cmax and CL. [ Time Frame: 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, and 24 hours (hrs) after the start of the infusion on Day 1 and Day 18. ]
The following PK parameters will be determined after administration of GSK221149 with and without EFZ 600 mg: Area under the plasma concentration-time curve (AUC)- from time zero to time t [AUC(0-t)] and from time zero extrapolated to infinite time [AUC(0-infinity)], maximum observed plasma concentration (Cmax) and clearance (CL). CL will be calculated for parent only.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 30, 2013)
  • Safety and tolerability of administration of GSK221149 with and without EFZ 600 mg as assessed by adverse event, concurrent medication review, clinical laboratory tests, ECG, and vital signs measurements. [ Time Frame: Up to 8 Weeks ]
    Clinical laboratory tests will include hematology, clinical chemistry and urinalysis parameters. Triplicate 12-lead ECGs will be obtained at the screening visit. Single 12-lead ECGs will be obtained at other time points during the study. Vital sign measurements will include systolic and diastolic blood pressure and pulse rate.
  • Plasma GSK221149 and GSK2847065 PK parameters of tmax, tlag and t1/2. [ Time Frame: 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, and 24 hours (hrs) after the start of the infusion on Day 1 and Day 18. ]
    The following PK parameters will be determined after administration of GSK221149 with and without EFZ 600 mg: time to Cmax (tmax), lag time (tlag), and terminal phase half-life (t1/2). The terminal half-life (t1/2) is defined as the time required for the plasma concentration of drug to reach half of its original concentration.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Retosiban (GSK221149) When Dosed With Efavirenz (EFZ)
Official Title  ICMJE To Evaluate the Pharmacokinetics, Safety and Tolerability of Retosiban (GSK221149) Co-administered With EFAVIRENZ
Brief Summary This will be a randomized single sequence open label study. This study is designed to determine if chronic dosing with efavirenz (EFZ) will have an effect on the pharmacokinetics (PK) of intravenously-administered retosiban in healthy volunteers. The study consists of screening (28 days), treatment (1 dosing session) and follow-up (7 to 14 days) period, and the total duration of study participation for each subject will be approximately 8 weeks. During the treatment period, subjects will be admitted to the clinical research unit the day before dosing (Day 1) and will remain until completion of the last assessment on Day 20. All subjects will receive on Day 1, a 6 milligrams (mg) bolus of retosiban for 5 minutes (min), followed by a 6 mg/hour (hr) infusion for 12 hrs. On Day 2, a washout day will occur. On Days 3-17, subjects will receive EFZ 600 mg once daily in the evening. On Day 18, subjects will receive a 6 mg bolus of retosiban for 5 mins, followed by a 6 mg/hr infusion for 12 hrs plus a 600 mg dose of EFZ.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Obstetric Labour, Premature
Intervention  ICMJE
  • Drug: Retosiban
    Retosiban will be supplied as clear colorless solution for infusion (300 mg in 20 mL via). Subject will receive loading dose of 6 mg over 5 min infusion followed by 6 mg/hour infusion for 12 hrs on Day 1 and Day 18.
  • Drug: EFZ 600 mg
    EZF 600 mg will be supplied as a yellow, capsular-shaped, film-coated tablet. Subjects will receive EFZ 600mg OD in the evening from Day 3 till Day 18.
Study Arms  ICMJE Experimental: Retosiban and EFZ
All subjects will receive on Day 1, a 6 mg bolus of retosiban for 5 min, followed by a 6 mg/hr infusion for 12 hrs. On Day 2 a washout day will occur. On Days 3-17, subjects will receive EFZ 600 mg OD dose of in the evening. On Day 18, subjects will receive a 6 mg bolus of retosiban for 5 mins, followed by a 6 mg/hr infusion for 12 hrs plus a 600 mg dose of EFZ.
Interventions:
  • Drug: Retosiban
  • Drug: EFZ 600 mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 9, 2014)
18
Original Estimated Enrollment  ICMJE
 (submitted: May 30, 2013)
16
Actual Study Completion Date  ICMJE September 26, 2013
Actual Primary Completion Date September 26, 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male/females aged between 18 and 45 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, 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 in consultation with the GlaxoSmithKline (GSK) Medical Monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Body weight >=50 kilogram (kg) and body mass index within the range 19-29.9 kg/m^2.
  • A female subject is eligible to participate if she is of: Child-bearing potential with negative pregnancy test as determined by serum human chorionic gonadotrophin (hCG) test at screening or prior to dosing; AND Agrees to use 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 the follow-up visit; OR has only same-sex partners, when this is her preferred and usual lifestyle.
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
  • Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5 x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Based on averaged corrected QT interval (QTc) values of triplicate electrocardiograms obtained over a brief recording period: QTc < 450 milliseconds (msec); or QTc < 480 msec in subjects with Bundle Branch Block.

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: For United States (US) sites: an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 gram of alcohol: 12 ounces (360 milliliter [mL]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
  • 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.
  • Has active suicidal plan/intent or has had active suicidal thoughts in the past 6 months. Has history of suicide attempt in the last 2 years or more than 1 lifetime suicide attempt.
  • Subjects with a history of seizures will be excluded from this trial.
  • Subjects with a history of severe or serious psychiatric disease requiring hospitalization, history of social ideation or attempt, or on ongoing psychiatric treatment will be excluded from this study.
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
  • 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.
  • A positive test for Human Immunodeficiency Virus (HIV) antibody.
  • Pregnant females as determined by positive serum hCG test at screening or prior to dosing.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • Lactating females.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01867996
Other Study ID Numbers  ICMJE 116073
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Current Responsible Party GlaxoSmithKline
Original Responsible Party Same as current
Current Study Sponsor  ICMJE GlaxoSmithKline
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP