- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01765569
A Pharmacokinetics Study to Investigate the Effect of Vemurafenib on Digoxin in Patients With BRAFV600 Mutation-Positive Metastatic Melanoma
August 24, 2015 updated by: Hoffmann-La Roche
A Phase I, Open-Label, Multicenter, 3-Period, Fixed-Sequence Study To Investigate The Effect Of Vemurafenib On The Pharmacokinetics Of A Single Dose Of Digoxin In Patients With BRAFV600 Mutation-Positive Metastatic Malignancy
This open-label, multi-center, three-period, one sequence study will investigate the effect of vemurafenib on the pharmacokinetics of digoxin in patients with unresectable BRAFV600-mutation positive metastatic melanoma or other malignant tumor type that harbors a V600-activating mutation of BRAF without acceptable standard treatment options.
Patients will receive multiple doses of vemurafenib in Periods B and C and a single dose of digoxin in Periods A and C. Eligible patients will have the option to continue treatment with vemurafenib as part of an extension study (NCT01739764).
The anticipated time on study treatment is approximately 36 days.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
29
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Minsk, Belarus, BU-220013
-
Minsk District, Belarus, 223040
-
Vitebsk, Belarus, BU-210603
-
-
-
-
-
Haifa, Israel, 31096
-
Tel Aviv, Israel, 6423906
-
Tel Hashomer, Israel, 52661
-
-
-
-
-
Daegu, Korea, Republic of, 702-911
-
Seoul, Korea, Republic of, 135-710
-
Seoul, Korea, Republic of, 110-774
-
-
-
-
-
Kazan, Russian Federation, 420029
-
Moscow, Russian Federation, 115478
-
St. Petersburg, Russian Federation, 197758
-
-
-
-
-
Johannesburg, South Africa, 2193
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male or female patients >= 18 years old
- Patients with either unresectable Stage IIIc or Stage IV metastatic melanoma positive for the BRAFV600 mutation or other malignant tumor type that harbors a V600-activating mutation of BRAF, as determined by results of cobas® 4800 BRAF V600 mutation test or a DNA sequencing method, and who have no acceptable standard treatment options
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- Life expectancy >= 12 weeks
- Full recovery from the effects of any major surgery or significant traumatic injury within 14 days prior to the first dose of study treatment
- Adequate hematologic and end organ function
- Female patients of childbearing potential and male patients with partners of childbearing potential must agree to always use two effective methods of contraception
- Negative serum pregnancy test within 7 days prior to commencement of dosing in women of childbearing potential
Exclusion Criteria:
- Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of first dose of study drug
- Prior anti-cancer therapy within 28 days before the first dose of study drug
- History of clinically significant cardiac or pulmonary dysfunction
- History of symptomatic congestive heart failure of any New York Heart Association class or serious cardiac arrhythmia requiring treatment
- History of myocardial infarction within 6 months prior to first dose of study drug
- Current dyspnea at rest, owing to complications of advanced malignancy or any requirement for supplemental oxygen to perform activities of daily living
- History of congenital long QT syndrome or QTc > 450 ms
- Current digoxin therapy or anticipated requirement to take digoxin therapy during the study
- Active central nervous system lesions
- Uncontrolled or poorly controlled diabetes
- Current severe, uncontrolled systemic disease
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Vemurafenib + Digoxin
Single oral dose of digoxin 0.25 mg tablet on Day 1 in Period A, followed by vemurafenib 960 mg tablet orally BID from Day 8 to Day 28 in Period B, and then single oral dose of digoxin 0.25 mg on Day 29, and vemurafenib 960 mg orally BID from Day 29 to Day 35 in Period C.
|
Participants received single oral dose of digoxin 0.25 mg tablet on Day 1 and Day 29.
Participants received vemurafenib 960 mg tablet orally BID from Day 8 to Day 35.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of Digoxin
Time Frame: Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
|
AUClast = Area under the plasma-concentration time curve from time zero to the last measurable plasma concentration which is presented in hour*nanogram per milliliter (hour*ng/mL).
Hour 0 (H0) signified pre-dose sampling.
|
Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
|
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Digoxin
Time Frame: Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
|
Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
|
|
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC24) of Digoxin
Time Frame: Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
|
Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
|
|
Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC168) of Digoxin
Time Frame: Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
|
Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
|
|
Maximum Plasma Concentration (Cmax) of Digoxin
Time Frame: Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
|
Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
|
|
Time to Maximum Plasma Concentration (Tmax) of Digoxin
Time Frame: Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
|
Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
|
|
Terminal Half-Life (t1/2) of Digoxin
Time Frame: Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
|
Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
|
|
Apparent Clearance (CL/F) of Digoxin
Time Frame: Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
|
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Clearance was estimated from population PK modeling.
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
|
Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
July 1, 2013
Primary Completion (Actual)
June 1, 2014
Study Completion (Actual)
June 1, 2014
Study Registration Dates
First Submitted
January 9, 2013
First Submitted That Met QC Criteria
January 9, 2013
First Posted (Estimate)
January 10, 2013
Study Record Updates
Last Update Posted (Estimate)
September 23, 2015
Last Update Submitted That Met QC Criteria
August 24, 2015
Last Verified
August 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Melanoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Protective Agents
- Cardiotonic Agents
- Protein Kinase Inhibitors
- Digoxin
- Vemurafenib
Other Study ID Numbers
- GO28394
- 2012-003459-13 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Malignant Melanoma, Neoplasms
-
Grupo Español Multidisciplinar de MelanomaGlaxoSmithKlineCompletedMalignant Melanoma Stage IV | Malignant Melanoma Stage IIIcSpain
-
Centre Hospitalier Universitaire de NiceUnknownMalignant Melanoma Stage III | Malignant Melanoma Stage IV
-
National Cancer Institute (NCI)TerminatedRecurrent Melanoma | Stage IV Melanoma | Acral Lentiginous Malignant Melanoma | Lentigo Maligna Malignant Melanoma | Nodular Malignant Melanoma | Solar Radiation-related Skin Melanoma | Superficial Spreading Malignant MelanomaUnited States
-
Hoffmann-La RocheCompletedMalignant Melanoma, NeoplasmsUnited States, South Africa, Croatia, Brazil, Egypt
-
Hoffmann-La RocheCompletedMalignant Melanoma, NeoplasmsBelgium, Spain, Germany, Netherlands, Finland
-
Hoffmann-La RocheCompletedMalignant Melanoma, CancerHungary
-
Lynn E. Spitler, MDGenentech, Inc.; Celgene CorporationCompletedMetastatic Malignant MelanomaUnited States
-
Hoffmann-La RocheCompletedMalignant Melanoma, NeoplasmsKorea, Republic of, Brazil, United States, Canada, Cyprus
-
Hoffmann-La RocheCompletedMalignant Melanoma, NeoplasmsSpain, New Zealand, Hungary, Serbia, Germany, Portugal, Netherlands, Greece, Australia
-
Steinar AamdalTerminatedMetastatic Malignant MelanomaNorway
Clinical Trials on Digoxin
-
University of California, Los AngelesCompleted
-
Hospital Ana NeryUnknownHeart FailureBrazil
-
Cairo UniversityCompletedAtrial Fibrillation
-
Genzyme, a Sanofi CompanyCompletedHealthy VolunteerUnited States
-
White, Katharine O'Connell, M.D., M.P.H.Society of Family PlanningCompleted
-
GlaxoSmithKlineCompleted
-
Assistance Publique - Hôpitaux de ParisUnknownKaposi' s Sarcoma | Classic Kaposi' s Sarcoma | Endemic Kaposi' s Sarcoma | Lymph Angio ProliferationsFrance
-
University of MonastirCompleted
-
Hoffmann-La RocheCompletedHealthy VolunteerUnited Kingdom
-
PfizerMedivation, Inc.CompletedAlzheimer Disease | Huntington DiseaseUnited States