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Dose Escalation Trial of Dalotuzumab (MK-0646) in Advanced Solid Tumors and Multiple Myeloma (MK-0646-001)

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ClinicalTrials.gov Identifier: NCT00701103
Recruitment Status : Completed
First Posted : June 19, 2008
Results First Posted : March 21, 2017
Last Update Posted : August 8, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Solid Tumor
Multiple Myeloma
Intervention Drug: Dalotuzumab
Enrollment 80
Recruitment Details Participants who were ≥18 years old, had metastatic or locally advanced solid tumors (including multiple myeloma) and failed to respond to standard therapy, or had progressed despite standard therapy, or for whom standard therapy did not exist were recruited for this study.
Pre-assignment Details  
Arm/Group Title Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL) Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL) Dalotuzumab 5 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (20 mg/mL) Dalotuzumab 15 mg/kg Q1W (10 mg/mL) Dalotuzumab 15 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q1W (10 mg/mL) Dalotuzumab 20 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q2W (20 mg/mL) Dalotuzumab 30 mg/kg Q3W (20 mg/mL)
Hide Arm/Group Description Participants received dalotuzumab 1.25 mg/kg (10 mg/mL) intravenous (IV) infusion 1 time every 1 week (Q1W). Participants received dalotuzumab 2.5 mg/kg (10 mg/mL) IV infusion Q1W. Participants received dalotuzumab 5 mg/kg (10 mg/mL) IV infusion Q1W. Participants received dalotuzumab 10 mg/kg (10 mg/mL) IV infusion Q1W. Participants received dalotuzumab 10 mg/kg (20 mg/mL) IV infusion Q1W. Participants received dalotuzumab 15 mg/kg (10 mg/mL) IV infusion Q1W. Participants received dalotuzumab 15 mg/kg (20 mg/ mL) IV infusion Q1W. Participants received dalotuzumab 20 mg/kg (10 mg/mL) IV infusion Q1W. Participants received dalotuzumab 20.0 mg/kg (20 mg/mL) IV infusion Q1W. Participants received dalotuzumab 20 mg/kg (20 mg/mL) IV infusion 1 time every 2 weeks (Q2W). Participants received dalotuzumab 30 mg/kg (20 mg/mL) IV infusion 1 time every 3 weeks (Q3W).
Period Title: Overall Study
Started 5 3 8 6 6 6 8 7 9 11 11
Completed 0 0 0 0 0 0 0 0 0 0 0
Not Completed 5 3 8 6 6 6 8 7 9 11 11
Reason Not Completed
Adverse Event             0             0             1             1             0             1             1             0             0             2             0
Progressive Disease             5             2             6             5             6             5             7             7             8             8             11
Withdrawal by Subject             0             1             1             0             0             0             0             0             0             0             0
Other             0             0             0             0             0             0             0             0             1             1             0
Arm/Group Title Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL) Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL) Dalotuzumab 5 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (20 mg/mL) Dalotuzumab 15 mg/kg Q1W (10 mg/mL) Dalotuzumab 15 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q1W (10 mg/mL) Dalotuzumab 20 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q2W (20 mg/mL) Dalotuzumab 30 mg/kg Q3W (20 mg/mL) Total
Hide Arm/Group Description Participants received dalotuzumab 1.25 mg/kg (10 mg/mL) IV infusion Q1W. Participants received dalotuzumab 2.5 mg/kg (10 mg/mL) IV infusion Q1W. Participants received dalotuzumab 5 mg/kg (10 mg/mL) IV infusion Q1W. Participants received dalotuzumab 10 mg/kg (10 mg/mL) IV infusion Q1W. Participants received dalotuzumab 10 mg/kg (20 mg/mL) IV infusion Q1W. Participants received dalotuzumab 15 mg/kg (10 mg/mL) IV infusion Q1W. Participants received dalotuzumab 15 mg/kg (20 mg/ mL) IV infusion Q1W. Participants received dalotuzumab 20 mg/kg (10 mg/mL) IV infusion Q1W. Participants received dalotuzumab 20.0 mg/kg (20 mg/mL) IV infusion Q1W. Participants received dalotuzumab 20 mg/kg (20 mg/mL) IV infusion Q2W. Participants received dalotuzumab 30 mg/kg (20 mg/mL) IV infusion Q3W. Total of all reporting groups
Overall Number of Baseline Participants 5 3 8 6 6 6 8 7 9 11 11 80
Hide Baseline Analysis Population Description
The population consisted of all participants who received at least one dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 5 participants 3 participants 8 participants 6 participants 6 participants 6 participants 8 participants 7 participants 9 participants 11 participants 11 participants 80 participants
69  (9) 60  (9) 68  (9) 56  (10) 53  (17) 49  (22) 54  (18) 46  (13) 52  (18) 55  (17) 52  (15) 55  (16)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 3 participants 8 participants 6 participants 6 participants 6 participants 8 participants 7 participants 9 participants 11 participants 11 participants 80 participants
Female
1
  20.0%
1
  33.3%
4
  50.0%
6
 100.0%
3
  50.0%
3
  50.0%
4
  50.0%
2
  28.6%
5
  55.6%
5
  45.5%
6
  54.5%
40
  50.0%
Male
4
  80.0%
2
  66.7%
4
  50.0%
0
   0.0%
3
  50.0%
3
  50.0%
4
  50.0%
5
  71.4%
4
  44.4%
6
  54.5%
5
  45.5%
40
  50.0%
1.Primary Outcome
Title Percentage of Participants Who Experienced One or More Dose-limiting Toxicities (DLTs)
Hide Description Toxicity was graded and recorded according to National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events version 3.0 (CTCAE 3.0). A DLT was defined as any Grade 3 or 4 toxicity. A Grade 3 toxicity was defined as severe or medically significant but not immediately life-threatening OR hospitalization or prolongation of hospitalization indicated OR disabling OR limiting self care activities of daily living. A Grade 4 toxicity was defined as: life-threatening consequences OR urgent intervention indicated. Participants were monitored for the occurrence of DLTs during the first 3 weeks of dosing with dalotuzumab.
Time Frame Up to 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The population consisted of all participants who received at least one dose of study drug.
Arm/Group Title Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL) Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL) Dalotuzumab 5 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (20 mg/mL) Dalotuzumab 15 mg/kg Q1W (10 mg/mL) Dalotuzumab 15 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q1W (10 mg/mL) Dalotuzumab 20 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q2W (20 mg/mL) Dalotuzumab 30 mg/kg Q3W (20 mg/mL)
Hide Arm/Group Description:
Participants received dalotuzumab 1.25 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 2.5 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 5 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 10 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 10 mg/kg (20 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 15 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 15 mg/kg (20 mg/ mL) IV infusion Q1W.
Participants received dalotuzumab 20 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 20.0 mg/kg (20 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 20 mg/kg (20 mg/mL) IV infusion Q2W.
Participants received dalotuzumab 30 mg/kg (20 mg/mL) IV infusion Q3W.
Overall Number of Participants Analyzed 5 3 8 6 6 6 8 7 9 11 11
Measure Type: Number
Unit of Measure: Percentage of Participants
0 0 13 0 0 0 0 0 0 0 0
2.Primary Outcome
Title Mean Terminal Half-life (t1/2) of Dalotuzumab
Hide Description Terminal half-life is defined as the time it takes for the blood plasma concentration of a substance to halve (plasma half-life). Blood samples for measurement of serum levels of dalotuzumab were obtained at: pre-dose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post infusion. For infusions >1 hour in duration, an additional sample was obtained at the mid-point of the infusion. Data presented are for the harmonic mean t1/2 for dalotuzumab.
Time Frame Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
The population consisted of all evaluable participants who received >90% of intended drug volume and had t1/2 pharmacokinetic measurements at Baseline and at least once during treatment.
Arm/Group Title Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL) Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL) Dalotuzumab 5 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (20 mg/mL) Dalotuzumab 15 mg/kg Q1W (10 mg/mL) Dalotuzumab 15 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q1W (10 mg/mL) Dalotuzumab 20 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q2W (20 mg/mL) Dalotuzumab 30 mg/kg Q3W (20 mg/mL)
Hide Arm/Group Description:
Participants received dalotuzumab 1.25 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 2.5 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 5 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 10 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 10 mg/kg (20 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 15 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 15 mg/kg (20 mg/ mL) IV infusion Q1W.
Participants received dalotuzumab 20 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 20.0 mg/kg (20 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 20 mg/kg (20 mg/mL) IV infusion Q2W.
Participants received dalotuzumab 30 mg/kg (20 mg/mL) IV infusion Q3W.
Overall Number of Participants Analyzed 5 3 8 6 3 6 8 7 9 11 11
Mean (Full Range)
Unit of Measure: Hours
67
(46 to 121)
79
(53 to 113)
83
(41 to 240)
169
(134 to 265)
100
(81 to 123)
95
(43 to 165)
110
(83 to 215)
129
(74 to 240)
120
(66 to 184)
106
(44 to 134)
142
(73 to 187)
3.Primary Outcome
Title Area Under the Time-concentration Curve From 0 to Infinity Hours (AUC0-∞) of Dalotuzumab
Hide Description AUC0-∞ represents the total drug exposure over time. Blood samples for measurement of serum levels of dalotuzumab were obtained at: Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion. For infusions >1 hour in duration, an additional sample was obtained at the mid-point of the infusion.
Time Frame Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
The population consisted of all evaluable participants who received >90% of intended drug volume and had AUC0-last pharmacokinetic measurements at Baseline and at least once during treatment.
Arm/Group Title Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL) Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL) Dalotuzumab 5 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (20 mg/mL) Dalotuzumab 15 mg/kg Q1W (10 mg/mL) Dalotuzumab 15 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q1W (10 mg/mL) Dalotuzumab 20 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q2W (20 mg/mL) Dalotuzumab 30 mg/kg Q3W (20 mg/mL)
Hide Arm/Group Description:
Participants received dalotuzumab 1.25 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 2.5 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 5 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 10 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 10 mg/kg (20 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 15 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 15 mg/kg (20 mg/ mL) IV infusion Q1W.
Participants received dalotuzumab 20 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 20.0 mg/kg (20 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 20 mg/kg (20 mg/mL) IV infusion Q2W.
Participants received dalotuzumab 30 mg/kg (20 mg/mL) IV infusion Q3W.
Overall Number of Participants Analyzed 5 3 8 6 3 6 8 7 9 11 11
Mean (Standard Deviation)
Unit of Measure: mg*hr/mL
1.6  (0.4) 3.7  (1.1) 12.9  (4.4) 28.9  (10.4) 18.4  (4.1) 39.4  (14.5) 28.8  (8.8) 52.7  (19.2) 44.3  (20.0) 45.9  (14.4) 92.6  (29.8)
4.Primary Outcome
Title Mean Serum Clearance of Dalotuzumab
Hide Description Clearance is defined as the volume of serum from which study drug was completely removed per unit of time. Blood samples for measurement of serum levels of dalotuzumab were obtained at: pre-dose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post infusion. For infusions >1 hour in duration, an additional sample was obtained at the mid-point of the infusion.
Time Frame Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
The population consisted of all evaluable participants who received >90% of intended drug volume and had mean serum clearance pharmacokinetic measurements at Baseline and at least once during treatment.
Arm/Group Title Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL) Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL) Dalotuzumab 5 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (20 mg/mL) Dalotuzumab 15 mg/kg Q1W (10 mg/mL) Dalotuzumab 15 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q1W (10 mg/mL) Dalotuzumab 20 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q2W (20 mg/mL) Dalotuzumab 30 mg/kg Q3W (20 mg/mL)
Hide Arm/Group Description:
Participants received dalotuzumab 1.25 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 2.5 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 5 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 10 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 10 mg/kg (20 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 15 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 15 mg/kg (20 mg/ mL) IV infusion Q1W.
Participants received dalotuzumab 20 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 20.0 mg/kg (20 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 20 mg/kg (20 mg/mL) IV infusion Q2W.
Participants received dalotuzumab 30 mg/kg (20 mg/mL) IV infusion Q3W.
Overall Number of Participants Analyzed 5 3 8 6 3 6 8 7 9 11 11
Mean (Standard Deviation)
Unit of Measure: mL/min/kg
0.013  (0.004) 0.012  (0.003) 0.007  (0.003) 0.006  (0.002) 0.009  (0.002) 0.007  (0.004) 0.010  (0.004) 0.007  (0.003) 0.009  (0.004) 0.008  (0.003) 0.006  (0.003)
5.Primary Outcome
Title Mean Trough Serum Concentration (Ctrough) of Dalotuzumab
Hide Description The lowest (trough) concentration of dalotuzumab prior to the next dose of dalotuzumab was measured.
Time Frame Pre-dose immediately prior to second infusion: 168 hours for Q1W, 336 hours for Q2W and 504 hours for Q3W dosing
Hide Outcome Measure Data
Hide Analysis Population Description
The population consisted of all evaluable participants who received >90% of intended drug volume and had mean trough serum concentration pharmacokinetic measurements at Baseline and at least once during treatment.
Arm/Group Title Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL) Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL) Dalotuzumab 5 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (20 mg/mL) Dalotuzumab 15 mg/kg Q1W (10 mg/mL) Dalotuzumab 15 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q1W (10 mg/mL) Dalotuzumab 20 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q2W (20 mg/mL) Dalotuzumab 30 mg/kg Q3W (20 mg/mL)
Hide Arm/Group Description:
Participants received dalotuzumab 1.25 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 2.5 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 5 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 10 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 10 mg/kg (20 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 15 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 15 mg/kg (20 mg/ mL) IV infusion Q1W.
Participants received dalotuzumab 20 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 20.0 mg/kg (20 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 20 mg/kg (20 mg/mL) IV infusion Q2W.
Participants received dalotuzumab 30 mg/kg (20 mg/mL) IV infusion Q3W.
Overall Number of Participants Analyzed 5 3 8 6 3 6 8 7 9 11 11
Mean (Standard Deviation)
Unit of Measure: ug/mL
2.4  (2.2) 7.2  (3.0) 21.2  (8.3) 54.8  (13.3) 45.2  (17.4) 81.2  (38.6) 59.6  (17.3) 110.5  (46.0) 87.3  (41.5) 57.0  (22.7) 70.4  (34.1)
6.Secondary Outcome
Title Change From Baseline in Insulin-like Growth Factor Receptor Type 1 (IGF-1R) Protein Expression Level H-score in Skin Samples
Hide Description IGF-1R expression was measured in pre- and post-dose skin biopsy samples using an immunohistochemistry (IHC) assay as a function of time and dose. Results were expressed as an IGF-1R membrane H-score which could range from 0 to 300; with a score of 0 representing the absence of IGF-1R expression and an H-score of 300 representing maximum IGF-1R expression. Changes in IGF-1R expression levels from Baseline are summarized for all participants for whom these paired data were available. A post-dose decrease in IGF-1R membrane H-score was an indication of target engagement by dalotuzumab. A larger decrease in H-score correlated with a greater target engagement.
Time Frame Predose in Cycle 1 (Baseline) and predose in Cycle 3 (Week 4)
Hide Outcome Measure Data
Hide Analysis Population Description
The population consisted of all evaluable participants who received >90% of intended drug volume and had skin IGF-1R pharmacodynamics measurements at Baseline and at least once during treatment. No data were available for the Dalotuzumab 30 mg/kg Q3W treatment group.
Arm/Group Title Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL) Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL) Dalotuzumab 5 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (10 mg/mL) Dalotuzumab 15 mg/kg Q1W (10 mg/mL) Dalotuzumab 20 mg/kg Q1W (10 mg/mL) Dalotuzumab 30 mg/kg Q3W (20 mg/mL)
Hide Arm/Group Description:
Participants received dalotuzumab 1.25 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 2.5 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 5 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 10 mg/kg IV infusion Q1W.
Participants received dalotuzumab 15 mg/kg IV infusion Q1W.
Participants received dalotuzumab 20 mg/kg IV infusion Q1W or Q2W.
Participants received dalotuzumab 30 mg/kg (20 mg/mL) IV infusion Q3W.
Overall Number of Participants Analyzed 3 3 7 11 10 15 0
Mean (Standard Deviation)
Unit of Measure: H-score
Baseline 186.7  (35.1) 203.3  (55.1) 218.6  (57.9) 171.8  (40.2) 182.0  (33.9) 146.3  (76.9)
Change from Baseline -1.7  (42.5) -11.7  (48.6) -20.0  (68.6) -2.7  (42.2) -39.0  (36.3) -27.0  (54.1)
7.Secondary Outcome
Title Change From Baseline in IGF-1R Protein Expression Level H-score in Tumor Samples
Hide Description IGF-1R expression was measured in pre- and post-dose tumor biopsy samples using an IHC assay as a function of time and dose. Results were expressed as an IGF-1R membrane H-score which could range from 0 to 300; with a score of 0 representing the absence of IGF-1R expression and an H-score of 300 representing maximum IGF-1R expression. Changes in IGF-1R expression levels from Baseline are summarized for all participants for whom these paired data were available. A post-dose decrease in IGF-1R membrane H-score was an indication of target engagement by dalotuzumab. A larger decrease in H-score correlated with a greater target engagement.
Time Frame Predose in Cycle 1 (Baseline) and predose in Cycle 3 (Week 4)
Hide Outcome Measure Data
Hide Analysis Population Description
The population consisted of all evaluable participants who received >90% of intended drug volume and had IGF-1R tumor pharmacodynamics measurements at Baseline and at least once during treatment. No data were available for the Dalotuzumab 2.5 mg/kg Q1W and Dalotuzumab 30 mg/kg Q3W treatment groups.
Arm/Group Title Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL) Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL) Dalotuzumab 5 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (10 mg/mL) Dalotuzumab 15 mg/kg Q1W (10 mg/mL) Dalotuzumab 20 mg/kg Q1W (10 mg/mL) Dalotuzumab 30 mg/kg Q3W (20 mg/mL)
Hide Arm/Group Description:
Participants received dalotuzumab 1.25 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 2.5 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 5 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 10 mg/kg IV infusion Q1W.
Participants received dalotuzumab 15 mg/kg IV infusion Q1W.
Participants received dalotuzumab 20 mg/kg IV infusion Q1W or Q2W.
Participants received dalotuzumab 30 mg/kg (20 mg/mL) IV infusion Q3W.
Overall Number of Participants Analyzed 2 0 5 4 7 15 0
Mean (Standard Deviation)
Unit of Measure: H-score
Baseline 145.0  (91.9) 84.0  (59.0) 110.0  (46.9) 134.3  (77.0) 152.5  (72.4)
Change from Baseline -80.0  (28.3) -16.0  (27.0) 10.0  (76.2) -30.0  (40.0) -40.8  (108.1)
8.Secondary Outcome
Title Percentage of Participants Who Developed a Serum Human-anti-humanized-antibody (HAHA) Response to Dalotuzumab
Hide Description It is thought that the formation of HAHAs may block efficacy by prematurely clearing dalotuzumab and limit the possibility of future dalotuzumab therapy. Blood samples for the measurement of serum levels of HAHAs were obtained prior to treatment with dalotuzumab, and pre-dose Week 2 (Q1W), pre-dose Week 3 (Q2W), pre-dose Week 4 (QW3), pre-dose Week 5 (Q1W/Q2W), pre-dose Week 7 (Q2W/Q3W), pre-dose Week 9 (Q2W), pre-dose Week 10 (QW3) and pre-dose every 4 subsequent weeks and end of treatment (post-study: 4 weeks after last dose of study drug).
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population consisted of all participants who received >90% of intended drug volume and had measurements at Baseline and at least once during treatment.
Arm/Group Title Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL) Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL) Dalotuzumab 5 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (20 mg/mL) Dalotuzumab 15 mg/kg Q1W (10 mg/mL) Dalotuzumab 15 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q1W (10 mg/mL) Dalotuzumab 20 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q2W (20 mg/mL) Dalotuzumab 30 mg/kg Q3W (20 mg/mL)
Hide Arm/Group Description:
Participants received dalotuzumab 1.25 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 2.5 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 5 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 10 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 10 mg/kg (20 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 15 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 15 mg/kg (20 mg/ mL) IV infusion Q1W.
Participants received dalotuzumab 20 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 20.0 mg/kg (20 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 20 mg/kg (20 mg/mL) IV infusion Q2W.
Participants received dalotuzumab 30 mg/kg (20 mg/mL) IV infusion Q3W.
Overall Number of Participants Analyzed 5 3 8 6 6 6 8 7 9 11 11
Measure Type: Number
Unit of Measure: Percentage of Participants
40 0 0 0 0 0 0 14 0 0 0
9.Secondary Outcome
Title Percentage of Participants Who Experienced a Complete Response (CR) or Partial Response (PR)
Hide Description Tumor responses were measured by using Response Evaluation Criteria in Solid Tumors (RECIST) criteria in participants with solid tumors and using European Group for Blood and Marrow Transplantation (EBMT) criteria in participants with multiple myeloma. RECIST criteria for CR: Disappearance of all target lesions. RECIST criteria for PR: ≥30% decrease in the sum of diameters of target lesions. EBMT criteria for CR: Disappearance of the original mAb protein from the blood and urine AND <5% plasma cells in the bone marrow AND no increase in the size or number of lytic bone lesions AND disappearance of soft tissue plasmacytomas AND normal serum calcium levels. EMBT criteria for PR: ≥50% reduction in the serum mAb protein level AND if a urine M-component is present, a reduction in 24-hour urinary light chain excretion by either ≥90% or to <200 mg AND ≥50% reduction in the size of soft tissue plasmacytomas AND no increase in size or number of lytic bone lesions.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The population consisted of all evaluable participants who received >90% of intended drug volume and had efficacy measurements at Baseline and at least once during treatment.
Arm/Group Title Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL) Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL) Dalotuzumab 5 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (20 mg/mL) Dalotuzumab 15 mg/kg Q1W (10 mg/mL) Dalotuzumab 15 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q1W (10 mg/mL) Dalotuzumab 20 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q2W (20 mg/mL) Dalotuzumab 30 mg/kg Q3W (20 mg/mL)
Hide Arm/Group Description:
Participants received dalotuzumab 1.25 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 2.5 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 5 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 10 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 10 mg/kg (20 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 15 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 15 mg/kg (20 mg/ mL) IV infusion Q1W.
Participants received dalotuzumab 20 mg/kg (10 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 20.0 mg/kg (20 mg/mL) IV infusion Q1W.
Participants received dalotuzumab 20 mg/kg (20 mg/mL) IV infusion Q2W.
Participants received dalotuzumab 30 mg/kg (20 mg/mL) IV infusion Q3W.
Overall Number of Participants Analyzed 5 3 8 6 6 6 8 7 9 11 11
Measure Type: Number
Unit of Measure: Percentage of Participants
0 0 0 0 0 0 0 0 0 0 0
Time Frame Up to 30 days after last dose of study drug (Up to 25 months)
Adverse Event Reporting Description The population consisted of all participants who received at least one dose of study drug.
 
Arm/Group Title Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL) Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL) Dalotuzumab 5 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (20 mg/mL) Dalotuzumab 15 mg/kg Q1W (10 mg/mL) Dalotuzumab 15 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q1W (10 mg/mL) Dalotuzumab 20 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q2W (20 mg/mL) Dalotuzumab 30 mg/kg Q3W (20 mg/mL)
Hide Arm/Group Description Participants received dalotuzumab 1.25 mg/kg (10 mg/mL) IV infusion Q1W. Participants received dalotuzumab 2.5 mg/kg (10 mg/mL) IV infusion Q1W. Participants received dalotuzumab 5 mg/kg (10 mg/mL) IV infusion Q1W. Participants received dalotuzumab 10 mg/kg (10 mg/mL) IV infusion Q1W. Participants received dalotuzumab 10 mg/kg (20 mg/mL) IV infusion Q1W. Participants received dalotuzumab 15 mg/kg (10 mg/mL) IV infusion Q1W. Participants received dalotuzumab 15 mg/kg (20 mg/mL) IV infusion Q1W. Participants received dalotuzumab 20 mg/kg (10 mg/mL) IV infusion Q1W. Participants received dalotuzumab 20 mg/kg (20 mg/mL) IV infusion Q1W. Participants received dalotuzumab 20 mg/kg (20 mg/mL) IV infusion Q2W. Participants received dalotuzumab 30 mg/kg (20 mg/mL) IV infusion Q3W.
All-Cause Mortality
Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL) Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL) Dalotuzumab 5 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (20 mg/mL) Dalotuzumab 15 mg/kg Q1W (10 mg/mL) Dalotuzumab 15 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q1W (10 mg/mL) Dalotuzumab 20 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q2W (20 mg/mL) Dalotuzumab 30 mg/kg Q3W (20 mg/mL)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Hide Serious Adverse Events
Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL) Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL) Dalotuzumab 5 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (20 mg/mL) Dalotuzumab 15 mg/kg Q1W (10 mg/mL) Dalotuzumab 15 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q1W (10 mg/mL) Dalotuzumab 20 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q2W (20 mg/mL) Dalotuzumab 30 mg/kg Q3W (20 mg/mL)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events 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   0/5 (0.00%)      0/3 (0.00%)      2/8 (25.00%)      2/6 (33.33%)      2/6 (33.33%)      3/6 (50.00%)      3/8 (37.50%)      0/7 (0.00%)      2/9 (22.22%)      3/11 (27.27%)      1/11 (9.09%)    
Gastrointestinal disorders                       
Abdominal pain  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/8 (12.50%)  1 0/7 (0.00%)  0 1/9 (11.11%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
Pancreatitis  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Subileus  1  0/5 (0.00%)  0 0/3 (0.00%)  0 1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
General disorders                       
Asthenia  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Infections and infestations                       
Skin bacterial infection  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0
Injury, poisoning and procedural complications                       
Femur fracture  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                       
Colon cancer  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/8 (12.50%)  1 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Ewing's sarcoma  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 2/6 (33.33%)  2 0/6 (0.00%)  0 1/8 (12.50%)  1 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Tumour pain  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0
Nervous system disorders                       
Convulsion  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Spinal cord compression  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Renal and urinary disorders                       
Renal failure acute  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0
Respiratory, thoracic and mediastinal disorders                       
Bronchospasm  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 1/9 (11.11%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
Dyspnoea  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 1/9 (11.11%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
Pleural effusion  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  2 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Skin and subcutaneous tissue disorders                       
Leukocytoclastic vasculitis  1  0/5 (0.00%)  0 0/3 (0.00%)  0 1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Vascular disorders                       
Deep vein thrombosis  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL) Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL) Dalotuzumab 5 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (10 mg/mL) Dalotuzumab 10 mg/kg Q1W (20 mg/mL) Dalotuzumab 15 mg/kg Q1W (10 mg/mL) Dalotuzumab 15 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q1W (10 mg/mL) Dalotuzumab 20 mg/kg Q1W (20 mg/mL) Dalotuzumab 20 mg/kg Q2W (20 mg/mL) Dalotuzumab 30 mg/kg Q3W (20 mg/mL)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events 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   5/5 (100.00%)      3/3 (100.00%)      6/8 (75.00%)      5/6 (83.33%)      4/6 (66.67%)      5/6 (83.33%)      8/8 (100.00%)      6/7 (85.71%)      8/9 (88.89%)      9/11 (81.82%)      11/11 (100.00%)    
Blood and lymphatic system disorders                       
Anaemia  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 1/6 (16.67%)  1 2/6 (33.33%)  4 0/6 (0.00%)  0 1/8 (12.50%)  1 1/7 (14.29%)  1 0/9 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0
Leukopenia  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Lymph node pain  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/8 (12.50%)  1 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Lymphopenia  1  1/5 (20.00%)  1 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Cardiac disorders                       
Sinus bradycardia  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 1/9 (11.11%)  2 0/11 (0.00%)  0 0/11 (0.00%)  0
Ear and labyrinth disorders                       
Tinnitus  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Eye disorders                       
Diplopia  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 1/9 (11.11%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
Gastrointestinal disorders                       
Abdominal pain  1  0/5 (0.00%)  0 1/3 (33.33%)  3 2/8 (25.00%)  2 1/6 (16.67%)  1 0/6 (0.00%)  0 2/6 (33.33%)  2 1/8 (12.50%)  1 2/7 (28.57%)  3 1/9 (11.11%)  2 0/11 (0.00%)  0 0/11 (0.00%)  0
Abdominal pain upper  1  0/5 (0.00%)  0 1/3 (33.33%)  1 1/8 (12.50%)  2 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Constipation  1  0/5 (0.00%)  0 0/3 (0.00%)  0 1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/8 (25.00%)  2 0/7 (0.00%)  0 1/9 (11.11%)  1 1/11 (9.09%)  1 2/11 (18.18%)  2
Diarrhoea  1  1/5 (20.00%)  1 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 2/11 (18.18%)  4
Dyspepsia  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 1/11 (9.09%)  1 2/11 (18.18%)  2
Nausea  1  1/5 (20.00%)  1 0/3 (0.00%)  0 2/8 (25.00%)  2 1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 1/8 (12.50%)  1 0/7 (0.00%)  0 0/9 (0.00%)  0 1/11 (9.09%)  2 3/11 (27.27%)  5
Odynophagia  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Oesophagitis  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Proctalgia  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Rectal haemorrhage  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Toothache  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/8 (12.50%)  1 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Vomiting  1  1/5 (20.00%)  1 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 2/11 (18.18%)  2 2/11 (18.18%)  4
General disorders                       
Asthenia  1  0/5 (0.00%)  0 2/3 (66.67%)  2 4/8 (50.00%)  5 2/6 (33.33%)  3 2/6 (33.33%)  2 0/6 (0.00%)  0 3/8 (37.50%)  5 2/7 (28.57%)  3 2/9 (22.22%)  2 3/11 (27.27%)  3 5/11 (45.45%)  6
Chest pain  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 2/6 (33.33%)  2 0/6 (0.00%)  0 1/6 (16.67%)  1 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Chills  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/8 (12.50%)  1 0/7 (0.00%)  0 1/9 (11.11%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
Fatigue  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 1/9 (11.11%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
Infusion related reaction  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0
Mucosal inflammation  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0
Oedema peripheral  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/8 (12.50%)  1 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Pain  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0
Pyrexia  1  0/5 (0.00%)  0 0/3 (0.00%)  0 1/8 (12.50%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/8 (12.50%)  1 0/7 (0.00%)  0 1/9 (11.11%)  1 0/11 (0.00%)  0 1/11 (9.09%)  1
Hepatobiliary disorders                       
Hyperbilirubinaemia  1  1/5 (20.00%)  2 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/8 (25.00%)  2 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Jaundice  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/8 (12.50%)  1 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Infections and infestations                       
Bronchiectasis  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Nasopharyngitis  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Pharyngitis  1  0/5 (0.00%)  0 0/3 (0.00%)  0 1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 1/9 (11.11%)  1 0/11 (0.00%)  0 1/11 (9.09%)  1
Respiratory tract infection  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Upper respiratory tract infection  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Urinary tract infection  1  0/5 (0.00%)  0 0/3 (0.00%)  0 1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 1/7 (14.29%)  1 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Injury, poisoning and procedural complications                       
Post procedural haemorrhage  1  1/5 (20.00%)  5 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Wound  1  0/5 (0.00%)  0 1/3 (33.33%)  1 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Investigations                       
Alanine aminotransferase increased  1  0/5 (0.00%)  0 0/3 (0.00%)  0 1/8 (12.50%)  1 1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 2/8 (25.00%)  3 0/7 (0.00%)  0 0/9 (0.00%)  0 1/11 (9.09%)  1 2/11 (18.18%)  2
Aspartate aminotransferase increased  1  2/5 (40.00%)  2 0/3 (0.00%)  0 3/8 (37.50%)  4 1/6 (16.67%)  2 1/6 (16.67%)  3 0/6 (0.00%)  0 2/8 (25.00%)  2 0/7 (0.00%)  0 0/9 (0.00%)  0 1/11 (9.09%)  1 2/11 (18.18%)  2
Blood alkaline phosphatase increased  1  1/5 (20.00%)  1 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Blood bilirubin increased  1  1/5 (20.00%)  1 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/8 (12.50%)  1 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Blood cholesterol increased  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  2
Blood creatinine increased  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  3 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Blood glucose decreased  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0
Blood glucose increased  1  0/5 (0.00%)  0 0/3 (0.00%)  0 1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 2/9 (22.22%)  5 2/11 (18.18%)  2 0/11 (0.00%)  0
Blood triglycerides increased  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  2
Gamma-glutamyltransferase increased  1  1/5 (20.00%)  1 0/3 (0.00%)  0 1/8 (12.50%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Haemoglobin decreased  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Platelet count decreased  1  0/5 (0.00%)  0 0/3 (0.00%)  0 1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Transaminases increased  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/8 (25.00%)  3 0/7 (0.00%)  0 1/9 (11.11%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
Metabolism and nutrition disorders                       
Anorexia  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 2/8 (25.00%)  3 0/7 (0.00%)  0 4/9 (44.44%)  5 0/11 (0.00%)  0 2/11 (18.18%)  2
Hyperglycaemia  1  0/5 (0.00%)  0 1/3 (33.33%)  1 2/8 (25.00%)  4 1/6 (16.67%)  3 1/6 (16.67%)  1 3/6 (50.00%)  6 2/8 (25.00%)  3 1/7 (14.29%)  2 3/9 (33.33%)  4 1/11 (9.09%)  3 2/11 (18.18%)  2
Hypertriglyceridaemia  1  0/5 (0.00%)  0 0/3 (0.00%)  0 1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Malnutrition  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0
Musculoskeletal and connective tissue disorders                       
Arthralgia  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 1/7 (14.29%)  1 1/9 (11.11%)  1 0/11 (0.00%)  0 2/11 (18.18%)  2
Back pain  1  0/5 (0.00%)  0 0/3 (0.00%)  0 3/8 (37.50%)  8 1/6 (16.67%)  1 2/6 (33.33%)  2 1/6 (16.67%)  2 1/8 (12.50%)  2 0/7 (0.00%)  0 1/9 (11.11%)  1 0/11 (0.00%)  0 3/11 (27.27%)  4
Bone pain  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 3/6 (50.00%)  4 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  2
Musculoskeletal chest pain  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/8 (12.50%)  2 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Musculoskeletal pain  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Myopathy  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Neck pain  1  1/5 (20.00%)  1 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Pain in extremity  1  0/5 (0.00%)  0 1/3 (33.33%)  1 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                       
Infected neoplasm  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0
Malignant ascites  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Tumour pain  1  0/5 (0.00%)  0 0/3 (0.00%)  0 1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/8 (0.00%)  0 0/7 (0.00%)  0 1/9 (11.11%)  1 1/11 (9.09%)  1 0/11 (0.00%)  0
Nervous system disorders                       
Dizziness  1  0/5 (0.00%)  0 0/3 (0.00%)  0 1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/8 (12.50%)  1 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Dysgeusia  1  1/5 (20.00%)  1 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Headache  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 1/9 (11.11%)  1 1/11 (9.09%)  1 2/11 (18.18%)  2
Loss of consciousness  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 1/9 (11.11%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
Paraesthesia  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 1/9 (11.11%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
Somnolence  1  0/5 (0.00%)  0 0/3 (0.00%)  0 1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/8 (12.50%)  1 0/7 (0.00%)  0 0/9 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0
Psychiatric disorders                       
Anxiety  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 1/11 (9.09%)  1 1/11 (9.09%)  1
Confusional state  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Depression  1  1/5 (20.00%)  1 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Insomnia  1  0/5 (0.00%)  0 0/3 (0.00%)  0 1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Renal and urinary disorders                       
Dysuria  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 1/9 (11.11%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
Reproductive system and breast disorders                       
Pelvic pain  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Vaginal haemorrhage  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0
Respiratory, thoracic and mediastinal disorders                       
Bronchospasm  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 1/9 (11.11%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
Cough  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 1/8 (12.50%)  2 2/7 (28.57%)  2 1/9 (11.11%)  1 1/11 (9.09%)  1 1/11 (9.09%)  2
Dysphonia  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Dyspnoea  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 0/8 (0.00%)  0 1/7 (14.29%)  1 3/9 (33.33%)  6 0/11 (0.00%)  0 0/11 (0.00%)  0
Haemoptysis  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 1/9 (11.11%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
Increased upper airway secretion  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Pleural effusion  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Productive cough  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 1/9 (11.11%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
Rhinorrhoea  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Skin and subcutaneous tissue disorders                       
Dry skin  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Pain of skin  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  2
Palmar-plantar erythrodysaesthesia syndrome  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0
Pruritus  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Rash  1  1/5 (20.00%)  1 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/8 (12.50%)  1 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Vascular disorders                       
Hypertension  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/8 (0.00%)  0 1/7 (14.29%)  1 1/9 (11.11%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
Lymphoedema  1  0/5 (0.00%)  0 0/3 (0.00%)  0 0/8 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/8 (12.50%)  1 0/7 (0.00%)  0 0/9 (0.00%)  0 0/11 (0.00%)  0 0/11 (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: NCT00701103    
Obsolete Identifiers: NCT00282737
Other Study ID Numbers: 0646-001
2007_660 ( Other Identifier: Merck Telerex Number )
First Submitted: June 17, 2008
First Posted: June 19, 2008
Results First Submitted: January 31, 2017
Results First Posted: March 21, 2017
Last Update Posted: August 8, 2018