CancerPhase 4NCT01205230
VEG113971: An Open-Label Study of the Effects of Ketoconazole or Esomeprazole on Pazopanib PK
A Phase 4 study testing pazopanib in people with Cancer, run by GlaxoSmithKline at 2 sites in United States.
Trial summary
The purpose of this study is to determine how dosing with ketoconazole (Nizoral) or esomeprazole (Nexium) affects the pharmacokinetics of oral pazopanib. The study will also test for safety of pazopanib when administered with ketoconazole or esomeprazole. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- pazopanib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2010to Aug 2011
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed, written informed consent
- 18 years of age or legal age of consent if greater than 18 years at the time of signing consent
- Histologically confirmed diagnosis of refractory or relapsed advanced solid tumor malignancy after standard therapy OR for which there is no standard therapy OR for which subject opts not to receive standard therapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate baseline organ function
- Subjects may not have had a transfusion within 7 days of screening assessment.
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- Subjects receiving anticoagulant therapy are eligible if their INR is stable and within the protocol recommended range.
- Male OR
- Female of non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had: a hysterectomy, a bilateral oophorectomy (ovariectomy), a bilateral tubal ligation, or is post-menopausal OR
- Non-pregnant Female of childbearing potential, including any female who has had a negative serum pregnancy test within 14 days prior to the first dose of study treatment, agrees to use acceptable contraceptive methods, used consistently and in accordance with both the product label and the instructions of the study physician. OR
- Female, if lactating, agrees to stop nursing prior to first dose until 14 days after last dose of study drug
- Able to swallow and retain orally administered medication
Who cannot join
- History or clinical evidence of central nervous system (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 first dose of study drug
- Clinically significant GI abnormalities that may increase the risk for GI bleeding including, but not limited to: active peptic ulcer disease, known intraluminal metastatic lesion/s with risk of bleeding inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease), 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.
- Clinically significant GI abnormalities that may affect absorption of investigational product including, but not limited to: malabsorption syndrome, major resection of the stomach or small bowel.
- Presence of uncontrolled infection.
- Corrected QT interval (QTc) >480 msec.
- History of any one or more of the following cardiovascular conditions within the past 6 months:
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- cardiac angioplasty or stenting, myocardial infarction,unstable angina,coronary artery bypass graft surgery, symptomatic peripheral vascular disease, Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA).
- Poorly controlled hypertension Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry.
- History of cerebrovascular accident including transient ischemic attack, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible.
- Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major).
- Evidence of active bleeding or bleeding diathesis.
- Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.
- Hemoptysis in excess of 2.5 mL (or one-half teaspoon) within 8 weeks of first dose of study drug.
- Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
- Treatment with any of the following anti-cancer therapies: radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or 5 half-lives of a drug (whichever is longer) prior to the first dose of pazopanib.
- Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 (graded by NCI-CTCAE, version 4.0), at the time of enrollment and/or that is progressing in severity, except alopecia as well as stable (>4 weeks) ≤Grade 2 neuropathy or rash.
- -Unable or unwilling to discontinue use of protocol-prohibited medications for at least 14 days or 5 half- lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study.
- -Use of HRT prior to study enrollment due to the potential for inhibition of cytochrome P450 enzymes that metabolize estrogens and progestins (Arm A female subjects only).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
GSK Investigational Site
Greenville, South Carolina, 29605
GSK Investigational Site
New Brunswick, New Jersey, 08901
About this study
Official title: An Open-Label Study to Evaluate the Effects of Ketoconazole and the Effects of Esomeprazole on the Pharmacokinetics of Orally Administered Repeat Doses of Pazopanib in Subjects With Solid Tumor Malignancies
The purpose of this study is to determine how dosing with ketoconazole (Nizoral) or esomeprazole (Nexium) affects the pharmacokinetics of oral pazopanib. The study will also test for safety of pazopanib when administered with ketoconazole or esomeprazole.
Read the detailed description
The study is a 2-arm, open-label, repeat-dose, single sequence, crossover, study designed to evaluate the effects of ketoconazole (Arm A) and esomeprazole (Arm B) on the pharmacokinetics (PK) of oral pazopanib in subjects with solid tumor malignancies. This study will compare the PK parameters of oral pazopanib and its metabolite concentrations when given alone and when co-administered with either ketoconazole (Arm A) or esomeprazole (Arm B). Safety assessments (physical examinations, vital signs, 12-lead electrocardiograms, Eastern Cooperative Oncology Group performance status, clinical laboratory assessments, and monitoring of adverse events) will also be evaluated during the study.
- Conditions
- Cancer
- Being tested
- pazopanib
- Keywords
- Esomeprazole, Pharmacogenetics, Pharmacokinetics, Ketoconazole, Pazopanib, Drug Interaction, Safety, Solid Tumors
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pazopanibDrug
Also called Votrient
Adenosine triphosphate (ATP)-competitive tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3, platelet derivative growth factor receptor (PDGFR)
| Study group | Role | What they receive |
|---|---|---|
| Pazonib+ketoconazole | Experimental | Administration of oral pazopanib 400mg (2 200-mg tablets) once-daily each morning for at least 7 consecutive doses during Period 1. Then administration of oral ketoconazole 400 mg (2 - 200 mg tablets) followed immediately by pazopanib 400 mg (2 -200 mg tablets) once-daily each morning for a total of 5 consecutive doses during Period 2. Receives: Drug: pazopanib |
| Pazonib+esomeprazole | Experimental | Subjects will receive orally administered pazopanib 800mg (4 - 200mg tablets) once-daily each morning for at least 7 consecutive doses in Period 1. In the evening on the last day of Period 1, subjects will take their initial dose of esomeprazole 40 mg (1 - 40 mg capsule) approximately 3 hours after the evening meal. Subjects will continue to receive pazopanib (each morning) and esomeprazole each evening once-daily for a total of 5 consecutive doses. Receives: Drug: pazopanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Pazopanib Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC[0-24]) of Pazopanib Alone and of Pazopanib in Combination With Ketoconazole and Esomeprazole
Blood samples for pharmacokinetic (PK) analysis of pazopanib were obtained at pre-dose (within 60 minutes prior to pazopanib administration) and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration. From the plasma concentration-time curve, the PK parameter AUC(0-24) was determined by standard non-compartmental analysis using WinNonlin. Plasma AUC(0-24) is a measure of the amount of drug a participant has been exposed to in 24 hours.
Measured: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained within 60 minutes prior to pazopanib administration and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration.
Plasma Maximum Observed Concentration (Cmax) of Pazopanib Alone and of Pazopanib in Combination With Ketoconazole and Esomeprazole
Blood samples for PK analysis of pazopanib were obtained at pre-dose (within 60 minutes prior to pazopanib administration) and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration. From the plasma concentration-time curve, the PK parameter Cmax was determined by standard non-compartmental analysis using WinNonlin. The concentration-time curve is the result of time points of blood sampling and its measured concentration of pazopanib in the plasma.
Measured: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained within 60 minutes prior to pazopanib administration and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration.
Time of Occurrence of Cmax (Tmax) of Pazopanib Alone and of Pazopanib in Combination With Ketoconazole and Esomeprazole
Blood samples for PK analysis of pazopanib were obtained at pre-dose (within 60 minutes prior to pazopanib administration) and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration. From the plasma concentration-time curve, the PK parameter tmax was determined by standard non-compartmental analysis using WinNonlin. Nominal data collection time points (TPs) were defined in the protocol; however, the actual data collection TP often differed slightly from the nominal TP for various reasons. This leads to medians and ranges that don't coincide with planned nominal data collection TPs.
Measured: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained within 60 minutes prior to pazopanib administration and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration.
Secondary outcomes (7)
Plasma Concentration at 24 Hours After Administration (C24) of Pazopanib Alone and of Pazopanib in Combination With Ketoconazole and Esomeprazole
Pazopanib plasma concentration-time data were analyzed by non-compartmental methods with WinNonlin. Calculations were based on the actual sampling times. From the plasma concentration-time data, the PK parameter C24 was determined.
Measured: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained 24 hours after administration of pazopanib.
Plasma AUC(0-24) for the Indicated Metabolites of Pazopanib When Administered Alone or in Combination With Ketoconazole and Ezomeprazole
Blood samples for PK analysis of the metabolites of pazopanib were obtained at pre-dose (within 60 minutes prior to pazopanib administration) and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration. From the plasma concentration-time curve, the PK parameter AUC(0-24) was determined by standard non-compartmental analysis using WinNonlin. Plasma AUC(0-24) is a measure of the amount of drug a participant has been exposed to in 24 hours.
Measured: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained within 60 minutes prior to pazopanib administration and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration.
Plasma Cmax for the Indicated Metabolites of Pazopanib When Administered Alone or in Combination With Ketoconazole and Ezomeprazole
Blood samples for PK analysis of the metabolites of pazopanib were obtained at pre-dose (within 60 minutes prior to pazopanib administration) and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration. From the plasma concentration-time curve, the PK parameter Cmax was determined by standard non-compartmental analysis using WinNonlin. The concentration-time curve is the result of time points of blood sampling and its measured concentration of pazopanib in the plasma.
Measured: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained within 60 minutes prior to pazopanib administration and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration.
Tmax for the Indicated Metabolites of Pazopanib When Administered Alone or in Combination With Ketoconazole and Ezomeprazole
Blood samples for PK analysis of pazopanib were obtained at pre-dose (within 60 minutes prior to pazopanib administration) and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration. From the plasma concentration-time curve, the PK parameter tmax was determined by standard non-compartmental analysis using WinNonlin. Nominal data collection time points (TPs) were defined in the protocol; however, the actual data collection TP often differed slightly from the nominal TP for various reasons. This leads to medians and ranges that don't coincide with planned nominal data collection TPs.
Measured: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained within 60 minutes prior to pazopanib administration and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration.
Plasma Ketoconazole Concentration at the Indicated Time Points
Blood samples for the determination of plasma ketoconazole concentrations were collected before (pre-dose [within 60 minutes prior to pazopanib administration]) and after the final pazopanib and ketoconazole dose (fifth dose) during Period 2 at the indicated time points, relative to pazopanib administration (at 1 and 2 hours after pazopanib administration). Blood samples were obtained via peripheral intravenous cannula or central line. Concentrations of ketoconazole were determined in plasma samples using the currently approved analytical methodology.
Measured: Day 5 of Period 2 (combination therapy). Blood samples were collected within 60 minutes prior to pazopanib administration and 1 and 2 hours after pazopanib administration.
Number of Participants With the Indicated Grade 3 or 4 Adverse Events (AEs)
AEs were graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0. Grades range from 0 (no toxicity) to 4 (life-threatening or disabling). A Grade 3 AE is severe; defined as considerable interference with the participant's daily activities, medical intervention/therapy required, and hospitalization possible. A Grade 4 AE is life-threatening; defined as extreme limitation in activity, significant medical intervention/therapy required, and hospitalization probable.
Measured: From Baseline (Day 1) to a maximum of 4 weeks after the last dose of study drug was administered (on Study Day 12)
Number of Participants With the Indicated Event of Dose Limiting Toxicity (DLT)
The following were considered DLTs only while participants were receiving pazopanib co-administered with either ketoconazole or esomeprazole: Grade 4 hematologic toxicities, excluding lymphopenia; and Grade 3/4 non-hematologic toxicities, excluding alopecia and nausea/vomiting/diarrhea for which adequate supportive therapy had not been instituted. Toxicities observed once co-administration of pazopanib with ketoconazole or esomeprazole was complete (after Day 5 of Period 2) could also be considered DLTs if judged to be relevant by the investigator and the GlaxoSmithKline Medical Monitor.
Measured: From Baseline (Day 1) to a maximum of 4 weeks after the last dose of study drug was administered (on Study Day 12)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2010 (estimated)
- Study startSep 2010
- Primary completionAug 2011
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01205230
- Sponsor's protocol ID
- 113971
- Status last verified
- May 2012
- First submitted
- 12 Aug 2010
- Last updated
- 22 May 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Tan AR, Gibbon DG, Stein MN, Lindquist D, Edenfield JW, Martin JC, Gregory C, Suttle AB, Tada H, Botbyl J, Stephenson JJ. Effects of ketoconazole and esomeprazole on the pharmacokinetics of pazopanib in patients with solid tumors. Cancer Chemother Pharmacol. 2013 Jun;71(6):1635-43. doi: 10.1007/s00280-013-2164-3. Epub 2013 May 1.
PubMed 23636448
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Study to Evaluate the Effects of Ketoconazole and the Effects of Esomeprazole on the Pharmacokinetics of Orally Administered Repeat Doses of Pazopanib in Subjects With Solid Tumor Malignancies
- ClinicalTrials.gov ID
- NCT01205230
- Acronym / sponsor ID
- 113971
- Conditions
- Cancer
- Keywords
- Esomeprazole, Pharmacogenetics, Pharmacokinetics, Ketoconazole, Pazopanib, Drug Interaction, Safety, Solid Tumors
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Sep 2010
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 20 Sep 2010 (estimated)
- Results
- Posted 24 Apr 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine how dosing with ketoconazole (Nizoral) or esomeprazole (Nexium) affects the pharmacokinetics of oral pazopanib. The study will also test for safety of pazopanib when administered with ketoconazole or esomeprazole.
Detailed description
The study is a 2-arm, open-label, repeat-dose, single sequence, crossover, study designed to evaluate the effects of ketoconazole (Arm A) and esomeprazole (Arm B) on the pharmacokinetics (PK) of oral pazopanib in subjects with solid tumor malignancies. This study will compare the PK parameters of oral pazopanib and its metabolite concentrations when given alone and when co-administered with either ketoconazole (Arm A) or esomeprazole (Arm B). Safety assessments (physical examinations, vital signs, 12-lead electrocardiograms, Eastern Cooperative Oncology Group performance status, clinical laboratory assessments, and monitoring of adverse events) will also be evaluated during the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pazonib+ketoconazole | Experimental | Drug: pazopanibAdministration of oral pazopanib 400mg (2 200-mg tablets) once-daily each morning for at least 7 consecutive doses during Period 1. Then administration of oral ketoconazole 400 mg (2 - 200 mg tablets) followed immediately by pazopanib 400 mg (2 -200 mg tablets) once-daily each morning for a total of 5 consecutive doses during Period 2. |
| Pazonib+esomeprazole | Experimental | Drug: pazopanibSubjects will receive orally administered pazopanib 800mg (4 - 200mg tablets) once-daily each morning for at least 7 consecutive doses in Period 1. In the evening on the last day of Period 1, subjects will take their initial dose of esomeprazole 40 mg (1 - 40 mg capsule) approximately 3 hours after the evening meal. Subjects will continue to receive pazopanib (each morning) and esomeprazole each evening once-daily for a total of 5 consecutive doses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Signed, written informed consent
- 18 years of age or legal age of consent if greater than 18 years at the time of signing consent
- Histologically confirmed diagnosis of refractory or relapsed advanced solid tumor malignancy after standard therapy OR for which there is no standard therapy OR for which subject opts not to receive standard therapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate baseline organ function
Key exclusion criteria (18 listed)
- History or clinical evidence of central nervous system (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 first dose of study drug
- Clinically significant GI abnormalities that may increase the risk for GI bleeding including, but not limited to: active peptic ulcer disease, known intraluminal metastatic lesion/s with risk of bleeding inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease), 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.
- Clinically significant GI abnormalities that may affect absorption of investigational product including, but not limited to: malabsorption syndrome, major resection of the stomach or small bowel.
- Presence of uncontrolled infection.
- Corrected QT interval (QTc) >480 msec.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| pazopanibAlso: VotrientAdenosine triphosphate (ATP)-competitive tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3, platelet derivative growth factor receptor (PDGFR) | Drug | Pazonib+esomeprazole, Pazonib+ketoconazole |
Primary outcome
Plasma Pazopanib Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC[0-24]) of Pazopanib Alone and of Pazopanib in Combination With Ketoconazole and Esomeprazole
Time frame: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained within 60 minutes prior to pazopanib administration and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration.
Blood samples for pharmacokinetic (PK) analysis of pazopanib were obtained at pre-dose (within 60 minutes prior to pazopanib administration) and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration. From the plasma concentration-time curve, the PK parameter AUC(0-24) was determined by standard non-compartmental analysis using WinNonlin. Plasma AUC(0-24) is a measure of the amount of drug a participant has been exposed to in 24 hours.
Plasma Maximum Observed Concentration (Cmax) of Pazopanib Alone and of Pazopanib in Combination With Ketoconazole and Esomeprazole
Time frame: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained within 60 minutes prior to pazopanib administration and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration.
Blood samples for PK analysis of pazopanib were obtained at pre-dose (within 60 minutes prior to pazopanib administration) and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration. From the plasma concentration-time curve, the PK parameter Cmax was determined by standard non-compartmental analysis using WinNonlin. The concentration-time curve is the result of time points of blood sampling and its measured concentration of pazopanib in the plasma.
Time of Occurrence of Cmax (Tmax) of Pazopanib Alone and of Pazopanib in Combination With Ketoconazole and Esomeprazole
Time frame: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained within 60 minutes prior to pazopanib administration and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration.
Blood samples for PK analysis of pazopanib were obtained at pre-dose (within 60 minutes prior to pazopanib administration) and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration. From the plasma concentration-time curve, the PK parameter tmax was determined by standard non-compartmental analysis using WinNonlin. Nominal data collection time points (TPs) were defined in the protocol; however, the actual data collection TP often differed slightly from the nominal TP for various reasons. This leads to medians and ranges that don't coincide with planned nominal data collection TPs.
7 secondary outcomes
Plasma Concentration at 24 Hours After Administration (C24) of Pazopanib Alone and of Pazopanib in Combination With Ketoconazole and Esomeprazole
Time frame: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained 24 hours after administration of pazopanib.
Plasma AUC(0-24) for the Indicated Metabolites of Pazopanib When Administered Alone or in Combination With Ketoconazole and Ezomeprazole
Time frame: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained within 60 minutes prior to pazopanib administration and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration.
Plasma Cmax for the Indicated Metabolites of Pazopanib When Administered Alone or in Combination With Ketoconazole and Ezomeprazole
Time frame: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained within 60 minutes prior to pazopanib administration and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration.
Tmax for the Indicated Metabolites of Pazopanib When Administered Alone or in Combination With Ketoconazole and Ezomeprazole
Time frame: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained within 60 minutes prior to pazopanib administration and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration.
Plasma Ketoconazole Concentration at the Indicated Time Points
Time frame: Day 5 of Period 2 (combination therapy). Blood samples were collected within 60 minutes prior to pazopanib administration and 1 and 2 hours after pazopanib administration.
Number of Participants With the Indicated Grade 3 or 4 Adverse Events (AEs)
Time frame: From Baseline (Day 1) to a maximum of 4 weeks after the last dose of study drug was administered (on Study Day 12)
Number of Participants With the Indicated Event of Dose Limiting Toxicity (DLT)
Time frame: From Baseline (Day 1) to a maximum of 4 weeks after the last dose of study drug was administered (on Study Day 12)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23636448Tan AR, Gibbon DG, Stein MN, Lindquist D, Edenfield JW, Martin JC, Gregory C, Suttle AB, Tada H, Botbyl J, Stephenson JJ. Effects of ketoconazole and esomeprazole on the pharmacokinetics of pazopanib in patients with solid tumors. Cancer Chemother Pharmacol. 2013 Jun;71(6):1635-43. doi: 10.1007/s00280-013-2164-3. Epub 2013 May 1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing pazopanib in people with Cancer, run by GlaxoSmithKline at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 May 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Apr 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma Pazopanib Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC[0-24]) of Pazopanib Alone and of Pazopanib in Combination With Ketoconazole and Esomeprazole (time frame: Day 7 of Period 1 (monotherapy) and Day 5 (Study Day 12) of Period 2 (combination therapy). Blood samples were obtained within 60 minutes prior to pazopanib administration and at 1, 2, 3, 4, 6, 8, and 24 hours after pazopanib administration.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01205230, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2012.