Pharmacokinetic and Safety of GSK573719 and GW642444 Administered Individually and Concurrently, With Verapamilin in Healthy Subjects

NCT ID: NCT01128634

Last Updated: 2017-06-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-04
• Study Completion Date: 2010-04-26

Brief Summary

The purpose of this study is to see if the Pharmacokinetics and the Safety Profile of GSK573719 and GSK573719/GW642444 are effected by concurrent dosing with the PGP inhibitor verapamil.

Conditions

Pulmonary Disease, Chronic Obstructive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

GSK573719

GSK573719

Group Type: OTHER

GSK573719

Intervention Type: DRUG

13 days dosing with GSK573719, once daily dosing from day 1 to 13, concurrent dosing with verapamil from day 9 to 13.

GSK573719/GW642444

GSK573719/GW642444

Group Type: OTHER

GW573719/GW573719

Intervention Type: DRUG

13 days dosing with GSK573719/GW573719, once daily dosing from day 1 to 13, concurrent dosing with verapamil from day 9 to 13.

Interventions

GSK573719

13 days dosing with GSK573719, once daily dosing from day 1 to 13, concurrent dosing with verapamil from day 9 to 13.

Intervention Type: DRUG

GW573719/GW573719

13 days dosing with GSK573719/GW573719, once daily dosing from day 1 to 13, concurrent dosing with verapamil from day 9 to 13.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• AST, ALT, alkaline phosphatase and bilirubin < 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
• Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
• A female subject is eligible to participate if she is of: non childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy, double oophorectomy or bilateral salpingectomy., or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 40 pg/ml (<140 pmol/L) or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
• Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until completion of the follow up visit.
• Body weight > 45 kg and BMI within the range 18 - 28 kg/m2 (inclusive).
• Capable of giving written informed consent and a signed and dated written informed consent is obtained, which includes compliance with the requirements and restrictions listed in the consent form.
• Normal spirometry (FEV1 ≥ 80% of predicted, FEV1/FVC ≥ 70%).
• Non-smokers (never smoked or not smoking for >6 months with <10 pack years history (Pack years = (cigarettes per day smoked/20) x number of years smoked))
• Available to complete the study

Exclusion Criteria

• Any clinically important abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, ECG (12-lead) or from 24hr Holter monitoring. If the Investigator and the GSK Medical Monitor agree that a finding is unlikely to introduce additional risk factors and will not interfere with the study procedures a subject can be included.
• A mean QTc(B) value at screening >450msec, or an ECG that is not suitable for QT measurements (e.g. LBBB or poorly defined termination of the T wave).
• A history of elevated resting blood pressure or a mean blood pressure higher than 140/90 mmHg at screening.
• A mean heart rate outside the range 40-90 bpm at screening.
• The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates and benzodiazepines. The detection of drugs with a legitimate medical use would not necessarily be an exclusion to study participation. The detection of alcohol would not be an exclusion at screening but would need to be negative pre-dose and during the study.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome).
• A positive test for HIV antibody (if testing required by local SOP's).
• History of regular alcohol consumption within 3months of the study defined as:

an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine.

• 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.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• History of sensitivity to any of the study medications, verapamil or components thereof, known allergy or hypersensitivity to milk protein or the excipients lactose monohydrate and MgSt, or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• The subject is unable to use the novel dry powder inhaler correctly.
• The subject has a known allergy or hypersensitivity to ipratropium bromide, tiotropium, atropine and any of its derivatives.
• Any adverse reaction including immediate or delayed hypersensitivity to any β2 agonist or sympathomimetic drug,.
• Subject is kept under regulatory of judicial order in an institution.
• Subject is mentally or legally incapacitated.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

London, , United Kingdom

Countries

United Kingdom

References

Mehta R, Kelleher D, Preece A, Hughes S, Crater G. Effect of verapamil on systemic exposure and safety of umeclidinium and vilanterol: a randomized and open-label study. Int J Chron Obstruct Pulmon Dis. 2013;8:159-67. doi: 10.2147/COPD.S40859. Epub 2013 Mar 27.

Reference Type: BACKGROUND

PMID: 23569370 (View on PubMed)

Study Documents

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

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

Other Identifiers

113950

Identifier Type: -

Identifier Source: org_study_id