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Phase 1 Study of Vorinostat and Bortezomib in Multiple Myeloma (MK-0683-015 EXT 1 (AM1))

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00111813
Recruitment Status : Completed
First Posted : May 26, 2005
Results First Posted : April 6, 2011
Last Update Posted : May 21, 2015
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Myeloma
Interventions Drug: vorinostat
Drug: bortezomib
Enrollment 34
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Vorinostat 200 mg + Bortezomib 0.7 mg/m^2 Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 Vorinostat 400 mg + Bortezomib 1.3 mg/m^2
Hide Arm/Group Description

Vorinostat capsules given twice daily (b.i.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).

Vorinostat capsules given b.i.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).

Vorinostat capsules given once daily (q.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Period Title: Overall Study
Started 3 3 10 6 6 6
Completed 0 0 0 1 0 0
Not Completed 3 3 10 5 6 6
Reason Not Completed
Adverse Event             1             2             4             2             2             2
Progressive disease             2             1             5             3             4             3
Lack of Efficacy             0             0             0             0             0             1
Not specified             0             0             1             0             0             0
Arm/Group Title All Participants
Hide Arm/Group Description

Vorinostat capsules given 200 mg b.i.d., 300 mg q.d., or 400 mg q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib 0.7 mg/m^2, 0.9 mg/m^2, 1.1 mg/m^2, or 1.3 mg/m^2 twice weekly on Days 1, 4, 8, and 11 or on Days 4, 8, 11, and 15 of each cycle, depending on dose level.

Overall Number of Baseline Participants 34
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 34 participants
60.6  (8.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants
Female
13
  38.2%
Male
21
  61.8%
1.Primary Outcome
Title Mean Duration of Treatment With Vorinostat
Hide Description

Event causing discontinuation from the study was defined as (1) progressive disease OR (2) intolerable toxicity.

Progressive disease was defined as:

  • >25% increase in the level of serum monoclonal paraprotein.
  • 25% increase in 24-hour urinary light chain excretion.
  • >25% increase in plasma cells in a bone marrow aspirate or on trephine

biopsy.

  • Development of new bone lesions or soft tissue plasmacytomas.
  • Development of hypercalcemia.

Intolerable toxicity was based on the clinical judgment of the investigator.

Time Frame Day 1 to an event causing discontinuation from the study, assessed up to 29 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Participants
Hide Arm/Group Description:

Vorinostat capsules given 200 mg b.i.d., 300 mg q.d., or 400 mg q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib 0.7 mg/m^2, 0.9 mg/m^2, 1.1 mg/m^2, or 1.3 mg/m^2 twice weekly on Days 1, 4, 8, and 11 or on Days 4, 8, 11, and 15 of each cycle, depending on dose level.

Overall Number of Participants Analyzed 34
Mean (Full Range)
Unit of Measure: Days
200 mg
4.6
(1 to 15)
300 mg
72.6
(28 to 210)
400 mg
107.1
(11 to 496)
2.Secondary Outcome
Title Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug
Hide Description An adverse experience (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience.
Time Frame Day 1 to disease progression, toxicity, or death, assessed up to 29 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vorinostat 200 mg + Bortezomib 0.7 mg/m^2 Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 Vorinostat 400 mg + Bortezomib 1.3 mg/m^2
Hide Arm/Group Description:

Vorinostat capsules given twice daily (b.i.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).

Vorinostat capsules given b.i.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).

Vorinostat capsules given once daily (q.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Overall Number of Participants Analyzed 3 3 10 6 6 6
Measure Type: Number
Unit of Measure: Participants
No dose modification 3 3 8 4 3 3
One dose modification 0 0 2 2 1 0
Two or more dose modifications 0 0 0 0 2 3
3.Secondary Outcome
Title Mean Time to First AE Resulting in a Dose Modification in Either Vorinostat or Bortezomib
Hide Description An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience.
Time Frame Day 1 to disease progression, toxicity, or death, assessed up to 29 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vorinostat 200 mg + Bortezomib 0.7 mg/m^2 Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 Vorinostat 400 mg + Bortezomib 1.3 mg/m^2
Hide Arm/Group Description:

Vorinostat capsules given twice daily (b.i.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).

Vorinostat capsules given b.i.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).

Vorinostat capsules given once daily (q.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Overall Number of Participants Analyzed 3 3 10 6 6 6
Mean (Standard Deviation)
Unit of Measure: Days
NA [1]   (NA) NA [1]   (NA) 58  (39) 58  (11) 128  (148) 32  (5)
[1]
No participants had a dose modification at this dose.
4.Secondary Outcome
Title Clinical AE Summary
Hide Description

An AE was defined as any unfavorable/unintended change in the structure/function/chemistry of the body temporally associated with the use of study drug, or any worsening of a preexisting condition.

A serious AE (SAE) was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a new cancer, or was an overdose.

Time Frame Day 1 up to disease progression, toxicity, or death, assessed up to 30 days after end of treatment (up to 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vorinostat 200 mg + Bortezomib 0.7 mg/m^2 Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 Vorinostat 400 mg + Bortezomib 1.3 mg/m^2
Hide Arm/Group Description:

Vorinostat capsules given twice daily (b.i.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).

Vorinostat capsules given b.i.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).

Vorinostat capsules given once daily (q.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Overall Number of Participants Analyzed 3 3 10 6 6 6
Measure Type: Number
Unit of Measure: Participants
With one or more AEs 3 3 10 6 6 6
With no AEs 0 0 0 0 0 0
With drug-related AEs 2 3 10 6 6 6
With Serious AEs (SAEs) 0 1 2 4 4 2
With drug-related SAEs 0 0 1 4 2 1
Who died 0 0 0 0 0 0
Who discontinued due to AEs 1 2 4 2 1 2
Who discontinued due to drug-related AEs 0 2 3 2 1 1
Who discontinued due to SAEs 0 0 1 2 0 1
Who discontinued due to drug-related SAEs 0 0 1 2 0 0
5.Secondary Outcome
Title Laboratory AE Summary
Hide Description

An AE was defined as any unfavorable/unintended change in the structure/function/chemistry of the body temporally associated with the use of study drug, or any worsening of a preexisting condition.

A SAE was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a new cancer, or was an overdose.

A lab (S)AE was any lab value considered clinically significant in the investigator's judgment.

Time Frame Day 1 up to disease progression, toxicity, or death, assessed up to 29 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vorinostat 200 mg + Bortezomib 0.7 mg/m^2 Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 Vorinostat 400 mg + Bortezomib 1.3 mg/m^2
Hide Arm/Group Description:

Vorinostat capsules given twice daily (b.i.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).

Vorinostat capsules given b.i.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).

Vorinostat capsules given once daily (q.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Overall Number of Participants Analyzed 3 3 10 6 6 6
Measure Type: Number
Unit of Measure: Participants
With one or more laboratory AEs 1 1 3 0 2 3
With no laboratory AEs 2 2 7 6 4 3
With drug-related laboratory AEs 1 0 2 0 1 3
With laboratory Serious AEs (SAEs) 0 0 0 0 0 0
With drug-related laboratory SAEs 0 0 0 0 0 0
Who died 0 0 0 0 0 0
Who discontinued due to laboratory AEs 0 0 0 0 0 0
Who discontinued due to drug-related lab AEs 0 0 0 0 0 0
Who discontinued due to laboratory SAEs 0 0 0 0 0 0
Who discontinued due to drug-related lab SAEs 0 0 0 0 0 0
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Vorinostat 200 mg + Bortezomib 0.7 mg/m^2 Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 Vorinostat 400 mg + Bortezomib 1.3 mg/m^2
Hide Arm/Group Description

Vorinostat capsules given twice daily (b.i.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).

Vorinostat capsules given b.i.d. Treatment in 21 day cycles

(participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).

Vorinostat capsules given once daily (q.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Vorinostat capsules given q.d. Treatment in 21 day cycles

(participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Vorinostat capsules given q.d. Treatment in 21 day cycles

(participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Vorinostat capsules given q.d. Treatment in 21 day cycles

(participants received vorinostat for 14 days followed by a 7 day break).

Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

All-Cause Mortality
Vorinostat 200 mg + Bortezomib 0.7 mg/m^2 Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 Vorinostat 400 mg + Bortezomib 1.3 mg/m^2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Vorinostat 200 mg + Bortezomib 0.7 mg/m^2 Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 Vorinostat 400 mg + Bortezomib 1.3 mg/m^2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/3 (0.00%)      1/3 (33.33%)      2/10 (20.00%)      4/6 (66.67%)      4/6 (66.67%)      2/6 (33.33%)    
Blood and lymphatic system disorders             
Neutropenia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Thrombocytopenia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 2/6 (33.33%)  3 0/6 (0.00%)  0
Gastrointestinal disorders             
Diarrhoea  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  3 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Nausea  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Vomiting  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
General disorders             
Chest pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Pyrexia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Infections and infestations             
Diverticulitis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0
Pneumonia  1  0/3 (0.00%)  0 1/3 (33.33%)  1 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Investigations             
Brain natriuretic peptide increased  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Metabolism and nutrition disorders             
Hypermagnesaemia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Musculoskeletal and connective tissue disorders             
Arthralgia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Pain in extremity  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Basal cell carcinoma  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0
Squamous cell carcinoma  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Nervous system disorders             
Amnesia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Headache  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Neuropathy peripheral  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Tremor  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Haemothorax  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vorinostat 200 mg + Bortezomib 0.7 mg/m^2 Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 Vorinostat 400 mg + Bortezomib 1.3 mg/m^2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      3/3 (100.00%)      10/10 (100.00%)      6/6 (100.00%)      6/6 (100.00%)      6/6 (100.00%)    
Blood and lymphatic system disorders             
Anaemia  1  0/3 (0.00%)  0 1/3 (33.33%)  2 3/10 (30.00%)  4 1/6 (16.67%)  1 1/6 (16.67%)  1 2/6 (33.33%)  4
Leukocytosis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Leukopenia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 2/6 (33.33%)  5 0/6 (0.00%)  0
Neutropenia  1  1/3 (33.33%)  2 1/3 (33.33%)  1 1/10 (10.00%)  1 0/6 (0.00%)  0 2/6 (33.33%)  4 1/6 (16.67%)  3
Thrombocytopenia  1  0/3 (0.00%)  0 3/3 (100.00%)  6 5/10 (50.00%)  12 2/6 (33.33%)  3 5/6 (83.33%)  19 4/6 (66.67%)  7
Cardiac disorders             
Palpitations  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Ear and labyrinth disorders             
Ear haemorrhage  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Middle ear effusion  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Eye disorders             
Conjunctivitis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1
Diplopia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Dry eye  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 2/6 (33.33%)  2 2/6 (33.33%)  3 0/6 (0.00%)  0
Eye irritation  1  0/3 (0.00%)  0 1/3 (33.33%)  2 0/10 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 1/6 (16.67%)  1
Eye oedema  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Eye pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1
Eye pruritus  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Lacrimation increased  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 3/6 (50.00%)  15 2/6 (33.33%)  3 2/6 (33.33%)  4
Ocular hyperaemia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  3 1/6 (16.67%)  3
Scintillating scotoma  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Vision blurred  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  3 1/6 (16.67%)  2 1/6 (16.67%)  1 1/6 (16.67%)  1
Gastrointestinal disorders             
Abdominal discomfort  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Abdominal distension  1  2/3 (66.67%)  6 1/3 (33.33%)  2 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Abdominal pain  1  1/3 (33.33%)  1 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Constipation  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 2/6 (33.33%)  3 4/6 (66.67%)  7 3/6 (50.00%)  11
Diarrhoea  1  0/3 (0.00%)  0 1/3 (33.33%)  5 8/10 (80.00%)  13 4/6 (66.67%)  18 6/6 (100.00%)  36 6/6 (100.00%)  17
Dry mouth  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/6 (33.33%)  2
Dyspepsia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 2/6 (33.33%)  2 1/6 (16.67%)  1
Flatulence  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  4
Gastritis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Gastrooesophageal reflux disease  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  2
Glossodynia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Haematochezia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Haemorrhoids  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Hiatus hernia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Lip blister  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Lip swelling  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Nausea  1  2/3 (66.67%)  2 3/3 (100.00%)  12 6/10 (60.00%)  13 5/6 (83.33%)  24 3/6 (50.00%)  19 6/6 (100.00%)  24
Oral discomfort  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Stomatitis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Toothache  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Vomiting  1  1/3 (33.33%)  1 2/3 (66.67%)  2 6/10 (60.00%)  7 3/6 (50.00%)  7 3/6 (50.00%)  4 5/6 (83.33%)  8
General disorders             
Asthenia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0
Chest discomfort  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 2/6 (33.33%)  3 0/6 (0.00%)  0 0/6 (0.00%)  0
Chest pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 2/6 (33.33%)  2
Chills  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Early satiety  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Face oedema  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Fatigue  1  2/3 (66.67%)  2 3/3 (100.00%)  6 5/10 (50.00%)  12 6/6 (100.00%)  20 2/6 (33.33%)  11 5/6 (83.33%)  33
Feeling of body temperature change  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Infusion site erythema  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Infusion site pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Injection site reaction  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Malaise  1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/10 (20.00%)  2 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Metaplasia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Mucosal inflammation  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Oedema  1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/10 (20.00%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Oedema peripheral  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 1/6 (16.67%)  2 1/6 (16.67%)  1 1/6 (16.67%)  5
Pain  1  1/3 (33.33%)  2 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Pyrexia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 5/10 (50.00%)  7 0/6 (0.00%)  0 2/6 (33.33%)  2 2/6 (33.33%)  2
Ulcer  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Infections and infestations             
Anogenital warts  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Candidiasis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Chest wall abscess  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Ear infection  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Eye infection  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Helicobacter infection  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Herpes simplex  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Herpes zoster  1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/10 (20.00%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Infection  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Localised infection  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Nasopharyngitis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 3/10 (30.00%)  3 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Oral herpes  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 2/6 (33.33%)  2
Pneumonia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Staphylococcal infection  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Tooth abscess  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Upper respiratory tract infection  1  0/3 (0.00%)  0 1/3 (33.33%)  1 2/10 (20.00%)  2 2/6 (33.33%)  6 2/6 (33.33%)  5 1/6 (16.67%)  1
Urinary tract infection  1  0/3 (0.00%)  0 0/3 (0.00%)  0 3/10 (30.00%)  4 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Vaginal infection  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Injury, poisoning and procedural complications             
Rib fracture  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Transfusion reaction  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Investigations             
Alanine aminotransferase increased  1  1/3 (33.33%)  2 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Aspartate aminotransferase increased  1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Blood alkaline phosphatase increased  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Blood bicarbonate decreased  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  3 0/6 (0.00%)  0
Blood creatinine increased  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/10 (0.00%)  0 0/6 (0.00%)  0 2/6 (33.33%)  5 0/6 (0.00%)  0
Blood glucose increased  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Blood lactate dehydrogenase increased  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Blood phosphorus increased  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Blood sodium decreased  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Heart rate increased  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Neutrophil count decreased  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1
Platelet count decreased  1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/10 (20.00%)  9 0/6 (0.00%)  0 0/6 (0.00%)  0 2/6 (33.33%)  4
Weight decreased  1  1/3 (33.33%)  1 2/3 (66.67%)  2 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1
Metabolism and nutrition disorders             
Decreased appetite  1  0/3 (0.00%)  0 1/3 (33.33%)  1 1/10 (10.00%)  1 0/6 (0.00%)  0 2/6 (33.33%)  2 4/6 (66.67%)  5
Dehydration  1  0/3 (0.00%)  0 2/3 (66.67%)  3 1/10 (10.00%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Hypercalcaemia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0
Hyperglycaemia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 2/6 (33.33%)  3 0/6 (0.00%)  0
Hyperkalaemia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0
Hyperlipidaemia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Hyperphosphataemia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  3 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Hypoalbuminaemia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Hypocalcaemia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Hypokalaemia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/10 (20.00%)  2 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Hypophosphataemia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Hypouricaemia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Type 2 diabetes mellitus  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Arthralgia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  2 1/6 (16.67%)  1 0/6 (0.00%)  0
Back pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 1/6 (16.67%)  2 2/6 (33.33%)  3 2/6 (33.33%)  2
Joint stiffness  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Muscle spasms  1  0/3 (0.00%)  0 0/3 (0.00%)  0 4/10 (40.00%)  4 2/6 (33.33%)  3 1/6 (16.67%)  1 1/6 (16.67%)  1
Muscular weakness  1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/10 (20.00%)  2 0/6 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0
Musculoskeletal chest pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Musculoskeletal pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Myalgia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 3/6 (50.00%)  3 0/6 (0.00%)  0 1/6 (16.67%)  9
Pain in extremity  1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/10 (20.00%)  2 0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Colon adenoma  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Squamous cell carcinoma  1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Nervous system disorders             
Dizziness  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  2 1/6 (16.67%)  6 1/6 (16.67%)  7 2/6 (33.33%)  6
Dysgeusia  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/6 (33.33%)  3
Dyskinesia  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Headache  1  0/3 (0.00%)  0 1/3 (33.33%)  1 2/10 (20.00%)  2 1/6 (16.67%)  1 1/6 (16.67%)  8 1/6 (16.67%)  1
Hypogeusia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Memory impairment  1  0/3 (0.00%)  0 1/3 (33.33%)  3 1/10 (10.00%)  1 3/6 (50.00%)  6 0/6 (0.00%)  0 1/6 (16.67%)  1
Neuralgia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Neuropathy peripheral  1  0/3 (0.00%)  0 1/3 (33.33%)  2 5/10 (50.00%)  8 2/6 (33.33%)  3 1/6 (16.67%)  2 1/6 (16.67%)  2
Paraesthesia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Somnolence  1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0
Tremor  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0
Psychiatric disorders             
Anxiety  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 2/6 (33.33%)  2 0/6 (0.00%)  0
Confusional state  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Depression  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Insomnia  1  1/3 (33.33%)  2 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  2 1/6 (16.67%)  1
Mental status changes  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Nightmare  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0
Renal and urinary disorders             
Bladder irritation  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Incontinence  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Cough  1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/10 (20.00%)  2 1/6 (16.67%)  1 2/6 (33.33%)  2 1/6 (16.67%)  2
Dysphonia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Dyspnoea  1  0/3 (0.00%)  0 0/3 (0.00%)  0 3/10 (30.00%)  4 3/6 (50.00%)  4 2/6 (33.33%)  5 0/6 (0.00%)  0
Dyspnoea exertional  1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/10 (20.00%)  2 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Epistaxis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Hiccups  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Nasal congestion  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Oropharyngeal pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 3/10 (30.00%)  3 1/6 (16.67%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0
Productive cough  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/10 (10.00%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1
Rhinorrhoea  1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/10 (20.00%)  2 0/6 (0.00%)  0 2/6 (33.33%)  2 1/6 (16.67%)  4
Sinus congestion  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Skin and subcutaneous tissue disorders             
Actinic keratosis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Alopecia  1  1/3 (33.33%)  1 1/3 (33.33%)  1 1/10 (10.00%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Dermatitis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Dry skin  1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/10 (20.00%)  2 1/6 (16.67%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0
Eczema  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Night sweats  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  5
Periorbital oedema  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  2 1/6 (16.67%)  2
Pruritus  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Rash macular  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Skin disorder  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Vascular disorders             
Flushing  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0
Hypertension  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/6 (33.33%)  2
Orthostatic hypotension  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/10 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
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 SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as

confidential must be deleted prior to submission. SPONSOR review can be expedited to meet publication guidelines.

Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00111813     History of Changes
Other Study ID Numbers: 0683-015
2005_018
First Submitted: May 25, 2005
First Posted: May 26, 2005
Results First Submitted: March 10, 2011
Results First Posted: April 6, 2011
Last Update Posted: May 21, 2015