- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01867996
A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Retosiban (GSK221149) When Dosed With Efavirenz (EFZ)
May 10, 2017 updated by: GlaxoSmithKline
To Evaluate the Pharmacokinetics, Safety and Tolerability of Retosiban (GSK221149) Co-administered With EFAVIRENZ
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
18
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Maryland
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Baltimore, Maryland, United States, 21225
- GSK Investigational Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 45 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
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.
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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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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.
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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.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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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.
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Up to 8 Weeks
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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.
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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.
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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.
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 11, 2013
Primary Completion (Actual)
September 26, 2013
Study Completion (Actual)
September 26, 2013
Study Registration Dates
First Submitted
May 30, 2013
First Submitted That Met QC Criteria
May 30, 2013
First Posted (Estimate)
June 4, 2013
Study Record Updates
Last Update Posted (Actual)
May 11, 2017
Last Update Submitted That Met QC Criteria
May 10, 2017
Last Verified
May 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 116073
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD 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.
Study Data/Documents
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Annotated Case Report Form
Information identifier: 116073Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Informed Consent Form
Information identifier: 116073Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Clinical Study Report
Information identifier: 116073Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Individual Participant Data Set
Information identifier: 116073Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Dataset Specification
Information identifier: 116073Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Study Protocol
Information identifier: 116073Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Statistical Analysis Plan
Information identifier: 116073Information comments: For additional information about this study please refer to the GSK Clinical Study Register
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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