NCT01765569

Brief Summary

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
29

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Jul 2013

Geographic Reach
5 countries

13 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 9, 2013

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 10, 2013

Completed
6 months until next milestone

Study Start

First participant enrolled

July 1, 2013

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2014

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

August 10, 2015

Completed
Last Updated

September 23, 2015

Status Verified

August 1, 2015

Enrollment Period

11 months

First QC Date

January 9, 2013

Results QC Date

July 14, 2015

Last Update Submit

August 24, 2015

Conditions

Malignant Melanoma, Neoplasms

Outcome Measures

Primary Outcomes (8)

  • Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of Digoxin

    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

    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

    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

    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

    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

    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

    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

    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

Study Arms (1)

Vemurafenib + Digoxin

EXPERIMENTAL

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.

Drug: DigoxinDrug: Vemurafenib

Interventions

DigoxinDRUG

Participants received single oral dose of digoxin 0.25 mg tablet on Day 1 and Day 29.

Vemurafenib + Digoxin
VemurafenibDRUG

Participants received vemurafenib 960 mg tablet orally BID from Day 8 to Day 35.

Vemurafenib + Digoxin

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (13)

Unknown Facility

Minsk, BU-220013, Belarus

Location

Unknown Facility

Minsk District, 223040, Belarus

Location

Unknown Facility

Vitebsk, BU-210603, Belarus

Location

Unknown Facility

Haifa, 31096, Israel

Location

Unknown Facility

Tel Aviv, 6423906, Israel

Location

Unknown Facility

Tel Litwinsky, 52661, Israel

Location

Unknown Facility

Kazan', 420029, Russia

Location

Unknown Facility

Moscow, 115478, Russia

Location

Unknown Facility

Saint Petersburg, 197758, Russia

Location

Unknown Facility

Johannesburg, 2193, South Africa

Location

Unknown Facility

Daegu, 702-911, South Korea

Location

Unknown Facility

Seoul, 110-774, South Korea

Location

Unknown Facility

Seoul, 135-710, South Korea

Location

MeSH Terms

Conditions

MelanomaNeoplasms

Interventions

DigoxinVemurafenib

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Digitalis GlycosidesCardenolidesCardiac GlycosidesCardanolidesSteroidsFused-Ring CompoundsPolycyclic CompoundsGlycosidesCarbohydratesSulfonamidesAmidesOrganic ChemicalsSulfonesSulfur CompoundsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Results Point of Contact

Title
Medical Communications
Organization
Organization: Hoffmann-LaRoche
genentech@druginfo.com
800-821-8590

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 9, 2013

First Posted

January 10, 2013

Study Start

July 1, 2013

Primary Completion

June 1, 2014

Study Completion

June 1, 2014

Last Updated

September 23, 2015

Results First Posted

August 10, 2015

Record last verified: 2015-08

Locations

IL(3)RU(3)BE(3)ZA(1)KR(3)