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A Pharmacokinetics Study to Investigate the Effect of Vemurafenib on Digoxin in Patients With BRAFV600 Mutation-Positive Metastatic Melanoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01765569
First received: January 9, 2013
Last updated: August 24, 2015
Last verified: August 2015
Results First Received: July 14, 2015  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Malignant Melanoma, Neoplasms
Interventions: Drug: Digoxin
Drug: Vemurafenib

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Vemurafenib + Digoxin

Single oral dose of digoxin 0.25 mg tablet on Day 1 in Period A, followed by vemurafenib 960 mg 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.

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

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


Participant Flow for 3 periods

Period 1:   Period A
    Vemurafenib + Digoxin  
STARTED     29  
COMPLETED     29  
NOT COMPLETED     0  

Period 2:   Period B
    Vemurafenib + Digoxin  
STARTED     29  
COMPLETED     28  
NOT COMPLETED     1  
Withdrawal by Subject                 1  

Period 3:   Period C
    Vemurafenib + Digoxin  
STARTED     28  
COMPLETED     27  
NOT COMPLETED     1  
Death                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
Vemurafenib + Digoxin

Single oral dose of digoxin 0.25 mg tablet on Day 1 in Period A, followed by vemurafenib 960 mg 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.

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

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


Baseline Measures
    Vemurafenib + Digoxin  
Number of Participants  
[units: participants]
  29  
Age  
[units: years]
Mean (Standard Deviation)
  47.8  (13.7)  
Gender  
[units: participants]
 
Female     16  
Male     13  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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 ]

2.  Primary:   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 ]

3.  Primary:   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 ]

4.  Primary:   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 ]

5.  Primary:   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 ]

6.  Primary:   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 ]

7.  Primary:   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 ]

8.  Primary:   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 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Communications
Organization: Organization: Hoffmann-LaRoche
phone: 800-821-8590
e-mail: genentech@druginfo.com



Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01765569     History of Changes
Other Study ID Numbers: GO28394
2012-003459-13 ( EudraCT Number )
Study First Received: January 9, 2013
Results First Received: July 14, 2015
Last Updated: August 24, 2015
Health Authority: United States: Food and Drug Administration