VEG111485: A QTc Study of Pazopanib

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00861029
First received: March 12, 2009
Last updated: January 22, 2011
Last verified: November 2010
  Purpose

This is a Phase I, randomized, double-blind, placebo-controlled, study to estimate the effects of daily oral dosing of 800 mg pazopanib on electrocardiographic parameters (QTc interval duration) as compared with placebo in subjects with solid tumors. Moxifloxacin, will serve as a positive control.


Condition Intervention Phase
Carcinoma, Renal Cell
Solid Tumors
Drug: Pazopanib
Other: Placebo for pazopanib
Drug: Moxifloxacin
Other: Placebo for moxifloxacin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: VEG111485: A Phase I, Randomized, Double-Blinded, Placebo-Controlled Study to Evaluate the Effect of Repeat Oral Doses ofPazopanib (GW786034) on Cardiac Conduction in Subjects withSolid Tumors

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change from baseline in QTcF interval at each time point on Study Day 9 (average of at least 3 Holter ECG replicates per time point) as compared with time-matched placebo. [ Time Frame: 11 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • ECG parameters: RR interval, QT, QTcB, heart rate, PR, QRS intervals and morphology. [ Time Frame: 11 days ] [ Designated as safety issue: Yes ]
  • Plasma pazopanib and metabolites (GSK1268992, GSK1268997 and GSK1071306) concentrations and PK parameters AUC(0-t), AUC(0-24), C24 Cmax and tmax as data permit. [ Time Frame: 11 days ] [ Designated as safety issue: No ]
  • Change from baseline in QTcF interval at each time point on Study Day 1 (average of at least 3 Holter ECG replicates per time point) as compared with time-matched placebo. [ Time Frame: 11 days ] [ Designated as safety issue: Yes ]
  • Plasma moxifloxacin concentrations and PK parameters AUC(0-t), AUC(0-∞), Cmax and tmax as data permit. [ Time Frame: 11 days ] [ Designated as safety issue: No ]
  • Safety parameters: AEs, vital signs, ECGs and clinical laboratory assessments. [ Time Frame: 11 days ] [ Designated as safety issue: Yes ]

Enrollment: 96
Study Start Date: March 2009
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pazopanib
Subjects will receive pazopanib during study
Drug: Pazopanib
Subjects treated with pazopanib
Drug: Moxifloxacin
Comparator for pazopanib
Other: Placebo for moxifloxacin
Placebo for moxifloxacin
Placebo
Placebo as a comparator to pazopanib
Other: Placebo for pazopanib
Control for comparison with pazopanib
Drug: Moxifloxacin
Comparator for pazopanib
Other: Placebo for moxifloxacin
Placebo for moxifloxacin

Detailed Description:

This is a Phase I, randomized, double-blind, placebo-controlled, parallel group study designed to estimate the effects of repeated, once daily oral dosing of pazopanib on electrocardiographic parameters with a particular focus on its effect on cardiac repolarization (QTc interval duration) as compared with placebo in subjects with solid tumors. Moxifloxacin, a drug known to cause mild QTc interval prolongation, is included as a positive control to validate the ability of the study to detect a small prolongation in the QTc interval. Digital 12-lead electrocardiograms (ECGs) will be extracted from continuous ECG recordings obtained via a Holter monitor. The effects of pazopanib and moxifloxacin on cardiac repolarization will be compared with placebo.

This study will also assess the pharmacokinetic-pharmacodynamic relationship between plasma concentrations of pazopanib and its metabolites and their effects, if any, on cardiac repolarization, specifically on the QT interval.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female, age 18 years or older, at the time of signing of the informed consent.
  • Has histologically or cytologically confirmed advanced solid tumor malignancy.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
  • Able to swallow and retain oral medication.
  • Adequate organ systems function.
  • Serum potassium level >4 mEq/L, magnesium level >1.7 mg/dL and total serum calcium level within normal limits (if albumin is <4.5 g/dL, albumin-corrected total serum calcium level should be within normal limits [see Appendix 7]). NOTE: Supplementation is permitted in order to meet this criterion. Subject should be retested following supplementation.
  • Subject is a woman of non-childbearing potential or willing to use acceptable contraception.
  • Subject is a man with a female partner of childbearing potential agrees to use contraception.
  • Subject, if sexually active, agrees to continue the recommended contraception method for the duration of treatment and for 28 days following discontinuation of treatment.
  • Capable of giving written informed consent.
  • The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.

Exclusion Criteria:

  • Any of the following ECG findings, QTcF interval >470 msec, PR interval >240 msec or ≤110msec, Bradycardia defined as sinus rate <50 beats per minute
  • Cardiac conduction abnormalities denoted by any of the following: Evidence of second-degree (type II) or third-degree atrioventricular block, Evidence of ventricular pre-excitation, Electrocardiographic evidence of complete left bundle branch block (LBBB), Intraventricular conduction delay with QRS duration >120 msec, Atrial fibrillation, Presence of cardiac pacemaker.
  • History of any one of the following cardiovascular conditions within the past 6 months: Class III or IV congestive heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, symptomatic peripheral vascular disease or other clinically significant cardiac disease.
  • For subjects with a history of myocardial infarction (>6 months ago), congestive heart failure (>6 months ago) or prior anthracycline exposure, left ventricular ejection fraction (LVEF) must be assessed within 28 days prior to the first dose of study drug by one of the following methods: multiple gated acquisition (MUGA) scan or echocardiogram (ECHO). Subjects with a measurement of LVEF <50% are excluded from participation in the study.
  • Personal or family history of long-QT syndrome.
  • History or clinical evidence of CNS metastases or leptomeningeal carcinomatosis, except for individuals who have previously treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 2 months prior to beginning study treatment.
  • Clinically significant gastrointestinal (GI) abnormalities that may affect the absorption of study drug including, but not limited to: malabsorption syndrome, major resection of the stomach or small bowel.
  • Clinically significant GI abnormalities that may increase the risk for GI bleeding including, but not limited to: active peptic ulcer disease, known intra-luminal metastatic lesion(s) with suspected bleeding, inflammatory bowel disease, ulcerative colitis or other GI conditions with increased risk of perforation, history of abdominal fistula, GI perforation or intra-abdominal abscess within 28 days prior to beginning study treatment.
  • Presence of uncontrolled infection.
  • Unable or unwilling to discontinue use of prohibited medications listed in Section 9.2 for at least 14 days prior to the first dose of study drug (see Section 9.2).
  • Poorly controlled hypertension [systolic blood pressure (SBP) >140 mmHg, or diastolic blood pressure (DBP) >90 mmHg].
  • History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
  • Evidence of active bleeding or bleeding diathesis.
  • Hemoptysis within 6 weeks prior to the first dose of study drug.
  • Known endobronchial lesion(s) or involvement of large pulmonary vessel(s) by tumor.
  • History of sensitivity or allergic reaction to moxifloxacin or any member of the quinolone class of antimicrobial agents.
  • Treatment with anti-cancer therapy (including chemotherapy, radiation therapy, immunotherapy, biologic therapy, investigational therapy, hormonal therapy, surgery or tumor embolization) within 14 days prior to the first dose of pazopanib.
  • History or presence of hepatic or renal disease or any other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
  • Prior major surgery or trauma within the past 28 days prior to the first dose of study drug and/or presence of any non-healing wound, fracture or ulcer.
  • Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00861029

Locations
United States, California
GSK Investigational Site
Duarte, California, United States, 91010
GSK Investigational Site
Santa Monica, California, United States, 90404
United States, Michigan
GSK Investigational Site
Detroit, Michigan, United States, 48201
United States, New Hampshire
GSK Investigational Site
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
GSK Investigational Site
New Brunswick, New Jersey, United States, 08901
United States, South Carolina
GSK Investigational Site
Greenville, South Carolina, United States, 29605
United States, Tennessee
GSK Investigational Site
Nashville, Tennessee, United States, 37203
United States, Washington
GSK Investigational Site
Tacoma, Washington, United States, 98405
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: E.D. Derilus; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00861029     History of Changes
Other Study ID Numbers: 111485
Study First Received: March 12, 2009
Last Updated: January 22, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
GW786034, pazopanib, moxifloxacin, ECG intervals and morphology, QTc, Holter monitor, pharmacokinetics, safety, cancer

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 22, 2014