VEG111485: A QTc Study of Pazopanib

NCT00861029 | Completed Phase 1

• 1 other identifier: 111485
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Carcinoma, Renal Cell

Keywords

GW786034, pazopanib, moxifloxacin, ECG intervals and morphology, QTc, Holter monitor, pharmacokinetics, safety, cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  11 days

Secondary Outcomes (5)

• ECG parameters: RR interval, QT, QTcB, heart rate, PR, QRS intervals and morphology.

  11 days

• 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.

  11 days

• 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.

  11 days

• Plasma moxifloxacin concentrations and PK parameters AUC(0-t), AUC(0-∞), Cmax and tmax as data permit.

  11 days

• Safety parameters: AEs, vital signs, ECGs and clinical laboratory assessments.

  11 days

Study Arms (2)

Pazopanib

EXPERIMENTAL

Subjects will receive pazopanib during study

Drug: Pazopanib; Drug: Moxifloxacin; Other: Placebo for moxifloxacin

Placebo

OTHER

Placebo as a comparator to pazopanib

Other: Placebo for pazopanib; Drug: Moxifloxacin; Other: Placebo for moxifloxacin

Interventions

Pazopanib DRUG

Subjects treated with pazopanib

Pazopanib

Placebo for pazopanib OTHER

Control for comparison with pazopanib

Placebo

Moxifloxacin DRUG

Comparator for pazopanib

Pazopanib; Placebo

Placebo for moxifloxacin OTHER

Placebo for moxifloxacin

Pazopanib; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (8)

GSK Investigational Site

Duarte, California, 91010, United States

Location

GSK Investigational Site

Santa Monica, California, 90404, United States

Location

GSK Investigational Site

Detroit, Michigan, 48201, United States

Location

GSK Investigational Site

Lebanon, New Hampshire, 03756, United States

Location

GSK Investigational Site

New Brunswick, New Jersey, 08901, United States

Location

GSK Investigational Site

Greenville, South Carolina, 29605, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37203, United States

Location

GSK Investigational Site

Tacoma, Washington, 98405, United States

Location

Related Publications (1)

• Heath EI, Infante J, Lewis LD, Luu T, Stephenson J, Tan AR, Kasubhai S, LoRusso P, Ma B, Suttle AB, Kleha JF, Ball HA, Dar MM. A randomized, double-blind, placebo-controlled study to evaluate the effect of repeated oral doses of pazopanib on cardiac conduction in patients with solid tumors. Cancer Chemother Pharmacol. 2013 Mar;71(3):565-73. doi: 10.1007/s00280-012-2030-8. Epub 2013 Jan 24.

  PMID: 23344712 BACKGROUND

Related Links

• Results for study 111485 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neoplasms

Interventions

pazopanib; Moxifloxacin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2009
• First Posted: March 13, 2009
• Study Start: March 19, 2009
• Primary Completion: February 15, 2010
• Study Completion: February 15, 2010
• Last Updated: November 14, 2017

Record last verified: 2017-11

Locations

US (8)