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

NCT01867996 | Completed Phase 1 DMC

• 1 other identifier: 116073
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Obstetric Labour, Premature

Keywords

Retosiban, Efavirenz, Induction

Outcome Measures

Primary Outcomes (1)

• Plasma GSK221149 (parent) and GSK2847065 (metabolite) PK parameters of AUC, Cmax and CL.

  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.

  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.

Secondary Outcomes (2)

• 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.

  Up to 8 Weeks

• Plasma GSK221149 and GSK2847065 PK parameters of tmax, tlag and t1/2.

  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.

Study Arms (1)

Retosiban and EFZ

EXPERIMENTAL

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.

Drug: Retosiban; Drug: EFZ 600 mg

Interventions

Retosiban DRUG

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.

Retosiban and EFZ

EFZ 600 mg DRUG

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.

Retosiban and EFZ

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male/females aged between 18 and 45 years of age inclusive, at the time of signing the informed consent.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Location

Related Links

• Results for study 116073 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Premature Birth

Interventions

GSK221149A

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2013
• First Posted: June 4, 2013
• Study Start: June 11, 2013
• Primary Completion: September 26, 2013
• Study Completion: September 26, 2013
• Last Updated: May 11, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)