Observational Pharmacokinetic Study Of GW679769 In Subjects With Renal Impairment

An Open-Label, Non-Randomized, Pharmacokinetic and Safety Study of Multiple Oral Doses of GW679769 in Subjects With Renal Impairment

The purpose of the study is to evaluate how subjects with mild or moderate kidney problems process or breakdown the study drug GW679769 in their bodies as compared to healthy subjects.

Study Overview

• Status: Completed
• Conditions: Vomiting
• Intervention / Treatment: Drug: Casopitant

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miramar, Florida, United States, 33025
      • GSK Investigational Site
    • Orlando, Florida, United States, 32809
      • GSK Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Healthy or have mild or moderate renal impairment.
• Females must be of non-childbearing potential(hysterectomy, bilateral oophorectomy, post-menopausal) OR childbearing and must have a negative pregnancy test and meet/comply with one of the following: abstinence, double-barrier contraception, vasectomized partner).
• Be negative for Hepatitis B and C.
• Have negative results on drug, alcohol and HIV tests.
• Have stable renal function.

Exclusion criteria:

• Have a peptic ulcer.
• Abuse drugs or alcohol.
• Are pregnant or lactating.
• Have heart failure.
• Have uncontrolled emesis.
• Have an infection.
• Have taken or received inducers or inhibitors of CYP3A4 or CYP3A5 within 14 days of study start.
• Active peptic ulcer disease.
• Digoxin use.
• Laboratory results that show low iron or pepsinogen levels, AST and CK level >1,5 ULN, or that show stool is positive for occult blood.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subjects receiving casopitant; Eligible subjects will receive a 100 milligrams oral dose of casopitant once daily for five consecutive days.	Drug: Casopitant; Casopitant oral tablets will be available with a dose of 50 milligrams.; Other Names: GW679769

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma drug concentration versus time curve from 0 to 24 hours (AUC[0-24]) of casopitant and GSK525060	Blood samples will be collected at the indicated time points for pharmacokinetic analysis.	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 16 hours on Day 1; pre-dose on Day 2, Day 3 and Day 4; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours on Day 5
Maximum observed concentration (Cmax) of casopitant and GSK525060	Blood samples will be collected at the indicated time points for pharmacokinetic analysis.	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 16 hours on Day 1; pre-dose on Day 2, Day 3 and Day 4; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours on Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to maximum observed plasma drug concentration (Tmax) of casopitant and GSK525060	Blood samples will be collected at the indicated time points for pharmacokinetic analysis.	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 16 hours on Day 1; pre-dose on Day 2, Day 3 and Day 4; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours on Day 5
Half-life of casopitant and GSK525060	Blood samples will be collected at the indicated time points for pharmacokinetic analysis.	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 16 hours on Day 1; pre-dose on Day 2, Day 3 and Day 4; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours on Day 5
Free fraction (percent unbound) of casopitant and GSK525060	Blood samples will be collected for assessment of protein binding of casopitant and GSK525060.	1,2,4 and 24 hours post-dose on Day 1; pre-dose,1,2,4 and 24 hours post-dose on Day 5
Number of subjects with adverse events (AEs) and serious adverse events (SAEs)	An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.	Up to Day 22
Number of subjects with abnormal values for blood pressure	Systolic (SBP) and diastolic blood pressure (DBP) will be measured.	Up to Day 22
Number of subjects with abnormal values for heart rate	Heart rate will be measured.	Up to Day 22
Number of subjects with abnormal findings after weight measurement	Weight evaluation will be performed as measure of safety.	Up to Day 22
Number of subjects having abnormal hematology laboratory parameters as a measure of safety	Hematology parameters will be analyzed as a measure of safety.	Up to Day 22
Number of subjects having abnormal clinical Chemistry laboratory parameters as a measure of safety	Clinical chemistry parameters will be analyzed as a measure of safety.	Up to Day 22
Number of subjects having abnormal values for urinalysis as a measure of safety	Urinalysis will be carried out as a measure of safety.	Up to Day 22
Number of subjects with abnormal findings after serological tests	Serological tests will be performed as a measure of safety.	Up to Day 22

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2006
• Primary Completion (Actual): August 22, 2008
• Study Completion (Actual): August 22, 2008

Study Registration Dates

• First Submitted: July 28, 2006
• First Submitted That Met QC Criteria: July 28, 2006
• First Posted (Estimate): August 1, 2006

Study Record Updates

• Last Update Posted (Actual): August 4, 2017
• Last Update Submitted That Met QC Criteria: August 3, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: renal impairment; emesis; GW679769; kidney problems
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Signs and Symptoms, Digestive; Vomiting; Renal Insufficiency; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Neurokinin-1 Receptor Antagonists; Casopitant
• Other Study ID Numbers: NKT102783

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

1. Annotated Case Report Form
   Information identifier: NKT102783
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: NKT102783
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Clinical Study Report
   Information identifier: NKT102783
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Study Protocol
   Information identifier: NKT102783
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: NKT102783
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: NKT102783
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: NKT102783
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register